FHIR IG analytics| Package | hl7.fhir.uv.epi-apac |
| Resource Type | Bundle |
| Id | Bundle-paxlovid-sgp-smpc-epi.json |
| FHIR Version | R5 |
No resources found
No resources found
No narrative content found in resource
FHIR
FHIRsmith{
"resourceType": "Bundle",
"id": "paxlovid-sgp-smpc-epi",
"identifier": {
"system": "https://www.hsa.gov.sg/epi/document-id",
"value": "PAXH-SIN-0126/0"
},
"type": "document",
"timestamp": "2026-07-01T11:21:25Z",
"entry": [
{
"fullUrl": "https://www.hsa.gov.sg/epi/Composition/comp-paxlovid-smpc",
"resource": {
"resourceType": "Composition",
"id": "comp-paxlovid-smpc",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Composition_comp-paxlovid-smpc\"> </a><p>Summary of Product Characteristics — PAXLOVID (nirmatrelvir/ritonavir) film-coated tablets. Singapore (HSA). Document PAXH-SIN-0126/0.</p></div>"
},
"contained": [
{
"resourceType": "Binary",
"id": "binary-image1",
"contentType": "image/png",
"data": 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"
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"
}
],
"identifier": [
{
"system": "https://www.hsa.gov.sg/epi/document-id",
"value": "PAXH-SIN-0126/0"
}
],
"status": "final",
"type": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/document-type",
"code": "smpc",
"display": "Summary of Product Characteristics"
}
]
},
"date": "2026-01-14",
"author": [
{
"reference": "Organization/org-owner",
"display": "Pfizer Inc."
}
],
"title": "PAXLOVID Film-Coated Tablets — Summary of Product Characteristics",
"language": "en",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid",
"display": "PAXLOVID film-coated tablets"
}
],
"section": [
{
"title": "Summary of Product Characteristics",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "smpc",
"display": "Summary of Product Characteristics"
}
]
},
"section": [
{
"title": "1. NAME OF THE MEDICINAL PRODUCT",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "1",
"display": "1. NAME OF THE MEDICINAL PRODUCT"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><span id=\"mpd-paxlovid\">PAXLOVID FILM-COATED TABLETS</span></p></div>"
},
"entry": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
]
},
{
"title": "2. QUALITATIVE AND QUANTITATIVE COMPOSITION",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "2",
"display": "2. QUALITATIVE AND QUANTITATIVE COMPOSITION"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Each pink <span id=\"ingr-nirmatrelvir\">nirmatrelvir</span> film-coated tablet contains 150 mg of nirmatrelvir.</p><p><img src=\"#binary-image1\" alt=\"Chemical structure\"/></p><p>Each white to off white <span id=\"ingr-ritonavir\">ritonavir</span> film-coated tablet contains 100 mg of ritonavir.</p><p><img src=\"#binary-image2\" alt=\"Chemical structure\"/></p></div>"
},
"entry": [
{
"reference": "Ingredient/ingr-nirmatrelvir"
},
{
"reference": "Ingredient/ingr-ritonavir"
}
]
},
{
"title": "3. PHARMACEUTICAL FORM",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "3",
"display": "3. PHARMACEUTICAL FORM"
}
]
},
"section": [
{
"title": "3.1. Nirmatrelvir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "3.1",
"display": "3.1. Nirmatrelvir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Film-coated tablet.</p><p>Pink, oval, with a dimension of approximately 17.6 mm in length and 8.6 mm in width debossed with ‘PFE’ on one side and ‘3CL’ on the other side.</p></div>"
}
},
{
"title": "3.2. Hetero Ritonavir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "3.2",
"display": "3.2. Hetero Ritonavir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>White to off white, capsule shaped, film-coated tablets, debossed with ‘H’ on one side and ‘R9’ on other side.</p></div>"
}
}
]
},
{
"title": "4. CLINICAL PARTICULARS",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4",
"display": "4. CLINICAL PARTICULARS"
}
]
},
"section": [
{
"title": "4.1. Therapeutic indications",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.1",
"display": "4.1. Therapeutic indications"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>PAXLOVID is indicated for the treatment of <span id=\"cud-ind-1\">mild-to-moderate Coronavirus Disease 2019 (COVID-19)</span> in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-ind-1"
}
]
},
{
"title": "4.2. Posology and method of administration",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.2",
"display": "4.2. Posology and method of administration"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets.</p><p>Nirmatrelvir must be co-administered with ritonavir. Failure to correctly co-administer nirmatrelvir with ritonavir may result in plasma levels of nirmatrelvir that are insufficient to achieve the desired therapeutic effect.</p></div>"
},
"section": [
{
"title": "4.2.1. Posology",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.2.1",
"display": "4.2.1. Posology"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The recommended dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) all taken together orally twice daily in the morning and in the evening for 5 days. PAXLOVID should be given as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset even if baseline COVID-19 symptoms are mild. If a patient requires hospitalization due to severe or critical COVID-19 after starting treatment with PAXLOVID, it is recommended that the patient should complete the full 5-day treatment course per the healthcare provider’s discretion.</p><p>If the patient misses a dose of PAXLOVID within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.</p></div>"
}
},
{
"title": "4.2.2. Patient selection",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.2.2",
"display": "4.2.2. Patient selection"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The following medical conditions or other factors place adult patients at high risk for progression to severe COVID-19:</p><p>Older age (e.g., 60 years of age and older)</p><p>Obesity or being overweight [e.g., body mass index (BMI) >25 kg/m<sup>2</sup>]</p><p>Current smoker</p><p>Chronic kidney disease</p><p>Diabetes</p><p>Immunosuppressive disease or immunosuppressive treatment</p><p>Cardiovascular disease (including congenital heart disease) or hypertension</p><p>Chronic lung disease [e.g., chronic obstructive pulmonary disease, asthma (moderate-to-severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension]</p><p>Sickle cell disease</p><p>Neurodevelopmental disorders (e.g., cerebral palsy, Down’s syndrome) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes and severe congenital anomalies)</p><p>Active cancer</p><p>Medical-related technological dependence not related to COVID-19 (e.g., tracheostomy, gastrostomy, or positive pressure ventilation)</p><p>Other medical conditions or factors (e.g., race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and are not limited to the medical conditions or factors listed above. Healthcare providers should consider the benefit-risk for an individual patient.</p></div>"
}
},
{
"title": "4.2.3. Special populations",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.2.3",
"display": "4.2.3. Special populations"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Pediatric population</i></p><p>The safety and efficacy of PAXLOVID have not been studied in patients younger than 18 years of age.</p><p><i>Renal impairment</i></p><p>No dosage adjustment is needed in patients with mild renal impairment [estimated glomerular filtration rate (eGFR) ≥60 to <90 mL/min].</p><p>In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) or with severe renal impairment (eGFR <30 mL/min) including those requiring hemodialysis, the dosage of PAXLOVID should be reduced as shown in Table 1. PAXLOVID should be administered at approximately the same time each day for 5 days. On days patients with severe renal impairment undergo hemodialysis, the PAXLOVID dose should be administered after hemodialysis (see section 5.2).</p><p><b>Table 1:</b><b>\t</b><b>Recommended dose and regimen for patients with renal impairment</b></p><table><thead><tr><th><b>Renal function</b></th><th><b>Days of treatment</b></th><th><b>Dose and dose frequency</b><b><sup>a</sup></b></th></tr></thead><tbody><tr><td>Moderate renal impairment<br/>(eGFR ≥30 to <60 mL/min)</td><td>Days 1-5</td><td>150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) <b>twice daily</b></td></tr><tr><td>Severe renal impairment<br/>(eGFR <30 mL/min) including those requiring hemodialysis<sup>b</sup></td><td>Day 1</td><td>300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) <b>once</b></td></tr><tr><td/><td>Days 2-5</td><td>150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) <b>once daily</b></td></tr><tr><td colspan=\"3\">Abbreviation: eGFR=estimated glomerular filtration rate.<br/>a.\tPAXLOVID should be administered at approximately the same time each day for 5 days.<br/>b.\tOn days of hemodialysis, the PAXLOVID dose should be administered after hemodialysis.</td></tr></tbody></table><p><b>Special attention for patients with MODERATE renal impairment:</b></p><p>Healthcare providers should pay special attention to dosing instructions for patients with <u><b>moderate</b></u> renal impairment and alert the patient that the daily dose pack provided may contain more nirmatrelvir and ritonavir tablets than needed for accurate dosing in these patients.</p><p>Therefore, patients with <u><b>moderate</b></u> renal impairment should be alerted that only one tablet of nirmatrelvir with one tablet of ritonavir should be taken every 12 hours for 5 days.</p><p><b>Special attention for patients with SEVERE renal impairment:</b></p><p>Healthcare providers should pay special attention to dosing instructions for patients with <u><b>severe</b></u> renal impairment and alert the patient that the daily dose pack provided may contain more nirmatrelvir and ritonavir tablets than needed for accurate dosing in these patients.</p><p>Therefore, patients with <u><b>severe</b></u> renal impairment should be alerted that two tablets of nirmatrelvir with one tablet of ritonavir should be taken once on Day 1 followed by one tablet of nirmatrelvir with one tablet of ritonavir once daily on Days 2 to 5.</p><p><i>Hepatic impairment</i></p><p>No dosage adjustment is needed in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.</p><p>No pharmacokinetic or safety data are available regarding the use of nirmatrelvir or ritonavir in participants with severe (Child-Pugh Class C) hepatic impairment; therefore, PAXLOVID is not recommended for use in patients with severe hepatic impairment (see section 5.2).</p><p><i>Concomitant therapy with ritonavir- or cobicistat-containing regimen</i></p><p>No dose adjustment is needed; the dose of PAXLOVID is 300 mg/100 mg twice daily for 5 days.</p><p>Patients diagnosed with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection who are receiving ritonavir- or cobicistat-containing regimen should continue their treatment as indicated.</p></div>"
}
},
{
"title": "4.2.4. Method of administration",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.2.4",
"display": "4.2.4. Method of administration"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>For oral use.</p><p>PAXLOVID can be taken with or without food (see section 5.2). The tablets should be swallowed whole and not chewed, broken, or crushed.</p></div>"
}
}
]
},
{
"title": "4.3. Contraindications",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3",
"display": "4.3. Contraindications"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity to the active substances (nirmatrelvir/ritonavir) or to any of the product excipients.</p><p>PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions (see section 4.5). Drugs listed in this section and section 4.5 are a guide and not considered a comprehensive list of all possible drugs that may be contraindicated with PAXLOVID.</p><p>Alpha 1-adrenoreceptor antagonist: alfuzosin</p><p>Antianginal: ranolazine</p><p>Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine</p><p>Anti-gout: colchicine</p><p>Antipsychotics: lurasidone, pimozide</p><p>Benign prostatic hyperplasia agents: silodosin</p><p>Cardiovascular agents: eplerenone, ivabradine</p><p>Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine</p><p>HMG-CoA reductase inhibitors: lovastatin, simvastatin</p><p>Immunosuppressants: voclosporin</p><p>Microsomal triglyceride transfer protein inhibitor: lomitapide</p><p>Migraine medications: eletriptan, ubrogepant</p><p>Mineralocorticoid receptor antagonists: finerenone</p><p>Non-opioid analgesic (selective blocker of Na<sub>v</sub>1.8 sodium channels): suzetrigine</p><p>Opioid antagonists: naloxegol</p><p>PDE5 inhibitor: sildenafil when used for pulmonary arterial hypertension (PAH)</p><p>Sedative/hypnotics: triazolam, oral midazolam</p><p>Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin</p><p>Vasopressin receptor antagonists: tolvaptan</p><p>PAXLOVID is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer<i> </i>(see section 4.5).</p><p>Anticancer drugs: apalutamide, enzalutamide</p><p>Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin</p><p>Antimycobacterials: rifampin, rifapentine</p><p>Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor</p><p>Herbal products: St. John’s Wort (<i>Hypericum perforatum</i>)</p></div>"
},
"section": [
{
"title": "4.3.1. Hypersensitivity to the active substances",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.1",
"display": "4.3.1. Hypersensitivity to the active substances"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Contraindicated in patients with a history of clinically significant hypersensitivity to <span id=\"cud-contra-hypersensitivity\">nirmatrelvir or ritonavir</span>.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-hypersensitivity"
}
]
},
{
"title": "4.3.2. alfuzosin (Alpha 1-adrenoreceptor antagonist)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.2",
"display": "4.3.2. alfuzosin (Alpha 1-adrenoreceptor antagonist)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-01-alfuzosin\">alfuzosin</span> (Alpha 1-adrenoreceptor antagonist) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-01-alfuzosin"
}
]
},
{
"title": "4.3.3. ranolazine (Antianginal)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.3",
"display": "4.3.3. ranolazine (Antianginal)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-02-ranolazine\">ranolazine</span> (Antianginal) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-02-ranolazine"
}
]
},
{
"title": "4.3.4. amiodarone (Antiarrhythmic)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.4",
"display": "4.3.4. amiodarone (Antiarrhythmic)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-03-amiodarone\">amiodarone</span> (Antiarrhythmic) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-03-amiodarone"
}
]
},
{
"title": "4.3.5. dronedarone (Antiarrhythmic)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.5",
"display": "4.3.5. dronedarone (Antiarrhythmic)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-04-dronedarone\">dronedarone</span> (Antiarrhythmic) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-04-dronedarone"
}
]
},
{
"title": "4.3.6. flecainide (Antiarrhythmic)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.6",
"display": "4.3.6. flecainide (Antiarrhythmic)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-05-flecainide\">flecainide</span> (Antiarrhythmic) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-05-flecainide"
}
]
},
{
"title": "4.3.7. propafenone (Antiarrhythmic)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.7",
"display": "4.3.7. propafenone (Antiarrhythmic)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-06-propafenone\">propafenone</span> (Antiarrhythmic) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-06-propafenone"
}
]
},
{
"title": "4.3.8. quinidine (Antiarrhythmic)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.8",
"display": "4.3.8. quinidine (Antiarrhythmic)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-07-quinidine\">quinidine</span> (Antiarrhythmic) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-07-quinidine"
}
]
},
{
"title": "4.3.9. colchicine (Anti-gout)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.9",
"display": "4.3.9. colchicine (Anti-gout)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-08-colchicine\">colchicine</span> (Anti-gout) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-08-colchicine"
}
]
},
{
"title": "4.3.10. lurasidone (Antipsychotics)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.10",
"display": "4.3.10. lurasidone (Antipsychotics)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-09-lurasidone\">lurasidone</span> (Antipsychotics) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-09-lurasidone"
}
]
},
{
"title": "4.3.11. pimozide (Antipsychotics)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.11",
"display": "4.3.11. pimozide (Antipsychotics)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-10-pimozide\">pimozide</span> (Antipsychotics) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-10-pimozide"
}
]
},
{
"title": "4.3.12. silodosin (Benign prostatic hyperplasia agents)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.12",
"display": "4.3.12. silodosin (Benign prostatic hyperplasia agents)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-11-silodosin\">silodosin</span> (Benign prostatic hyperplasia agents) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-11-silodosin"
}
]
},
{
"title": "4.3.13. eplerenone (Cardiovascular agents)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.13",
"display": "4.3.13. eplerenone (Cardiovascular agents)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-12-eplerenone\">eplerenone</span> (Cardiovascular agents) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-12-eplerenone"
}
]
},
{
"title": "4.3.14. ivabradine (Cardiovascular agents)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.14",
"display": "4.3.14. ivabradine (Cardiovascular agents)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-13-ivabradine\">ivabradine</span> (Cardiovascular agents) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-13-ivabradine"
}
]
},
{
"title": "4.3.15. dihydroergotamine (Ergot derivatives)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.15",
"display": "4.3.15. dihydroergotamine (Ergot derivatives)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-14-dihydroergotamine\">dihydroergotamine</span> (Ergot derivatives) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-14-dihydroergotamine"
}
]
},
{
"title": "4.3.16. ergotamine (Ergot derivatives)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.16",
"display": "4.3.16. ergotamine (Ergot derivatives)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-15-ergotamine\">ergotamine</span> (Ergot derivatives) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-15-ergotamine"
}
]
},
{
"title": "4.3.17. methylergonovine (Ergot derivatives)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.17",
"display": "4.3.17. methylergonovine (Ergot derivatives)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-16-methylergonovine\">methylergonovine</span> (Ergot derivatives) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-16-methylergonovine"
}
]
},
{
"title": "4.3.18. lovastatin (HMG-CoA reductase inhibitors)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.18",
"display": "4.3.18. lovastatin (HMG-CoA reductase inhibitors)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-17-lovastatin\">lovastatin</span> (HMG-CoA reductase inhibitors) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-17-lovastatin"
}
]
},
{
"title": "4.3.19. simvastatin (HMG-CoA reductase inhibitors)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.19",
"display": "4.3.19. simvastatin (HMG-CoA reductase inhibitors)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-18-simvastatin\">simvastatin</span> (HMG-CoA reductase inhibitors) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-18-simvastatin"
}
]
},
{
"title": "4.3.20. voclosporin (Immunosuppressants)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.20",
"display": "4.3.20. voclosporin (Immunosuppressants)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-19-voclosporin\">voclosporin</span> (Immunosuppressants) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-19-voclosporin"
}
]
},
{
"title": "4.3.21. lomitapide (Microsomal triglyceride transfer protein inhibitor)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.21",
"display": "4.3.21. lomitapide (Microsomal triglyceride transfer protein inhibitor)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-20-lomitapide\">lomitapide</span> (Microsomal triglyceride transfer protein inhibitor) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-20-lomitapide"
}
]
},
{
"title": "4.3.22. eletriptan (Migraine medications)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.22",
"display": "4.3.22. eletriptan (Migraine medications)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-21-eletriptan\">eletriptan</span> (Migraine medications) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-21-eletriptan"
}
]
},
{
"title": "4.3.23. ubrogepant (Migraine medications)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.23",
"display": "4.3.23. ubrogepant (Migraine medications)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-22-ubrogepant\">ubrogepant</span> (Migraine medications) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-22-ubrogepant"
}
]
},
{
"title": "4.3.24. finerenone (Mineralocorticoid receptor antagonists)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.24",
"display": "4.3.24. finerenone (Mineralocorticoid receptor antagonists)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-23-finerenone\">finerenone</span> (Mineralocorticoid receptor antagonists) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-23-finerenone"
}
]
},
{
"title": "4.3.25. suzetrigine (Non-opioid analgesic (selective blocker of Nav1.8 sodium channels))",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.25",
"display": "4.3.25. suzetrigine (Non-opioid analgesic (selective blocker of Nav1.8 sodium channels))"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-24-suzetrigine\">suzetrigine</span> (Non-opioid analgesic (selective blocker of Nav1.8 sodium channels)) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-24-suzetrigine"
}
]
},
{
"title": "4.3.26. naloxegol (Opioid antagonists)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.26",
"display": "4.3.26. naloxegol (Opioid antagonists)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-25-naloxegol\">naloxegol</span> (Opioid antagonists) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-25-naloxegol"
}
]
},
{
"title": "4.3.27. sildenafil when used for pulmonary arterial hypertension (PAH) (PDE5 inhibitor)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.27",
"display": "4.3.27. sildenafil when used for pulmonary arterial hypertension (PAH) (PDE5 inhibitor)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-26-sildenafil-when-used-for-pulmonary-arterial-hype\">sildenafil when used for pulmonary arterial hypertension (PAH)</span> (PDE5 inhibitor) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-26-sildenafil-when-used-for-pulmonary-arterial-hype"
}
]
},
{
"title": "4.3.28. triazolam (Sedative/hypnotics)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.28",
"display": "4.3.28. triazolam (Sedative/hypnotics)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-27-triazolam\">triazolam</span> (Sedative/hypnotics) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-27-triazolam"
}
]
},
{
"title": "4.3.29. oral midazolam (Sedative/hypnotics)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.29",
"display": "4.3.29. oral midazolam (Sedative/hypnotics)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-28-oral-midazolam\">oral midazolam</span> (Sedative/hypnotics) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-28-oral-midazolam"
}
]
},
{
"title": "4.3.30. flibanserin (Serotonin receptor 1A agonist/serotonin receptor 2A antagonist)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.30",
"display": "4.3.30. flibanserin (Serotonin receptor 1A agonist/serotonin receptor 2A antagonist)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-29-flibanserin\">flibanserin</span> (Serotonin receptor 1A agonist/serotonin receptor 2A antagonist) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-29-flibanserin"
}
]
},
{
"title": "4.3.31. tolvaptan (Vasopressin receptor antagonists)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.31",
"display": "4.3.31. tolvaptan (Vasopressin receptor antagonists)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-30-tolvaptan\">tolvaptan</span> (Vasopressin receptor antagonists) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-30-tolvaptan"
}
]
},
{
"title": "4.3.32. apalutamide (Anticancer drugs)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.32",
"display": "4.3.32. apalutamide (Anticancer drugs)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-31-apalutamide\">apalutamide</span> (Anticancer drugs) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-31-apalutamide"
}
]
},
{
"title": "4.3.33. enzalutamide (Anticancer drugs)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.33",
"display": "4.3.33. enzalutamide (Anticancer drugs)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-32-enzalutamide\">enzalutamide</span> (Anticancer drugs) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-32-enzalutamide"
}
]
},
{
"title": "4.3.34. carbamazepine (Anticonvulsant)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.34",
"display": "4.3.34. carbamazepine (Anticonvulsant)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-33-carbamazepine\">carbamazepine</span> (Anticonvulsant) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-33-carbamazepine"
}
]
},
{
"title": "4.3.35. phenobarbital (Anticonvulsant)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.35",
"display": "4.3.35. phenobarbital (Anticonvulsant)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-34-phenobarbital\">phenobarbital</span> (Anticonvulsant) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-34-phenobarbital"
}
]
},
{
"title": "4.3.36. primidone (Anticonvulsant)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.36",
"display": "4.3.36. primidone (Anticonvulsant)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-35-primidone\">primidone</span> (Anticonvulsant) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-35-primidone"
}
]
},
{
"title": "4.3.37. phenytoin (Anticonvulsant)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.37",
"display": "4.3.37. phenytoin (Anticonvulsant)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-36-phenytoin\">phenytoin</span> (Anticonvulsant) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-36-phenytoin"
}
]
},
{
"title": "4.3.38. rifampin (Antimycobacterials)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.38",
"display": "4.3.38. rifampin (Antimycobacterials)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-37-rifampin\">rifampin</span> (Antimycobacterials) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-37-rifampin"
}
]
},
{
"title": "4.3.39. rifapentine (Antimycobacterials)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.39",
"display": "4.3.39. rifapentine (Antimycobacterials)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-38-rifapentine\">rifapentine</span> (Antimycobacterials) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-38-rifapentine"
}
]
},
{
"title": "4.3.40. lumacaftor/ivacaftor (Cystic fibrosis transmembrane conductance regulator potentiators)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.40",
"display": "4.3.40. lumacaftor/ivacaftor (Cystic fibrosis transmembrane conductance regulator potentiators)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-39-lumacaftor-ivacaftor\">lumacaftor/ivacaftor</span> (Cystic fibrosis transmembrane conductance regulator potentiators) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-39-lumacaftor-ivacaftor"
}
]
},
{
"title": "4.3.41. St. John’s Wort (Hypericum perforatum) (Herbal products)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.3.41",
"display": "4.3.41. St. John’s Wort (Hypericum perforatum) (Herbal products)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Co-administration with <span id=\"cud-contra-40-st-john-s-wort-hypericum-perforatum\">St. John’s Wort (Hypericum perforatum)</span> (Herbal products) is contraindicated.</p></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-contra-40-st-john-s-wort-hypericum-perforatum"
}
]
}
]
},
{
"title": "4.4. Special warnings and precautions for use",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.4",
"display": "4.4. Special warnings and precautions for use"
}
]
},
"section": [
{
"title": "4.4.1. Risk of serious adverse reactions due to drug interactions",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.4.1",
"display": "4.4.1. Risk of serious adverse reactions due to drug interactions"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Initiation of PAXLOVID, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A.</p><p>Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PAXLOVID, respectively.</p><p>These interactions may lead to:</p><p>Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications.</p><p>Clinically significant adverse reactions from greater exposures of PAXLOVID.</p><p>Loss of therapeutic effect of PAXLOVID and possible development of viral resistance.</p><p>Severe, life-threatening, and fatal adverse reactions due to drug interactions have been reported in patients treated with PAXLOVID.</p><p>See Table 2 for drugs that are contraindicated for concomitant use with nirmatrelvir/ritonavir and for potentially significant interactions with other drugs (see section 4.5; also see section 4.3 for drugs that are contraindicated for concomitant use). Potential for drug interactions should be considered prior to and during PAXLOVID therapy; concomitant medications should be reviewed during PAXLOVID therapy and the patient should be monitored for the adverse reactions associated with the concomitant medications.</p><p><i>Co-administration of PAXLOVID with calcineurin inhibitors and mTOR inhibitors</i></p><p>Consultation of a multidisciplinary group (e.g., involving physicians, specialists in immunosuppressive therapy, and/or specialists in clinical pharmacology) is required to handle the complexity of this co-administration by closely and regularly monitoring immunosuppressant blood concentrations and adjusting the dose of the immunosuppressant in accordance with the latest guidelines (see section 4.5).</p></div>"
}
},
{
"title": "4.4.2. Hypersensitivity reactions",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.4.2",
"display": "4.4.2. Hypersensitivity reactions"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Anaphylaxis, hypersensitivity reactions, and serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported with PAXLOVID (see section 4.8). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.</p></div>"
}
},
{
"title": "4.4.3. Hepatotoxicity",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.4.3",
"display": "4.4.3. Hepatotoxicity"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.</p></div>"
}
},
{
"title": "4.4.4. Risk of HIV-1 resistance development",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.4.4",
"display": "4.4.4. Risk of HIV-1 resistance development"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Because nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.</p></div>"
}
}
]
},
{
"title": "4.5. Interaction with other medicinal products and other forms of interaction",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.5",
"display": "4.5. Interaction with other medicinal products and other forms of interaction"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>PAXLOVID (nirmatrelvir/ritonavir) is a strong inhibitor of CYP3A and an inhibitor of CYP2D6, P-gp and OATP1B1. Co-administration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse reactions.</p><p>Drugs that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in exposure when co-administered with nirmatrelvir/ritonavir. Thus, co-administration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated (see section 4.3).</p><p>Co-administration of other CYP3A4 substrates that may lead to potentially significant interaction should be considered only if the benefits outweigh the risks (see Table 2).</p><p>Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect.</p><p>Drugs listed in Table 2 are a guide and not considered a comprehensive list of all possible drugs that may interact with nirmatrelvir/ritonavir. The healthcare provider should consult appropriate references for comprehensive information.</p><p><b>Table </b><b>2</b><b>:</b><b>\t</b><b>Established and other potentially significant drug interactions</b></p><table><thead><tr><th><b>Drug Class</b></th><th><b>Drugs within Class</b></th><th><b>Effect on Concentration</b></th><th><b>Clinical Comments</b></th></tr></thead><tbody><tr><td>Alpha 1-adrenoreceptor antagonist</td><td>alfuzosin</td><td>↑ alfuzosin</td><td>Co-administration contraindicated due to potential hypotension (see section 4.3).</td></tr><tr><td>Alpha 1-adrenoreceptor antagonist</td><td>tamsulosin</td><td>↑ tamsulosin</td><td>Avoid concomitant use with PAXLOVID.</td></tr><tr><td>Antianginal</td><td>ranolazine</td><td>↑ ranolazine</td><td>Co-administration contraindicated due to potential for serious and/or life-threatening reactions (see section 4.3).</td></tr><tr><td>Antiarrhythmics</td><td>amiodarone,<br/>dronedarone,<br/>flecainide,<br/>propafenone,<br/>quinidine</td><td>↑ antiarrhythmic</td><td>Co-administration contraindicated due to potential for cardiac arrhythmias (see section 4.3).</td></tr><tr><td>Antiarrhythmics</td><td>lidocaine (systemic),<br/>disopyramide</td><td>↑ antiarrhythmic</td><td>Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.</td></tr><tr><td>Anticancer drugs</td><td>apalutamide,<br/>enzalutamide</td><td>↓ nirmatrelvir/ritonavir</td><td>Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</td></tr><tr><td>Anticancer drugs</td><td>abemaciclib,<br/>ceritinib,<br/>dasatinib,<br/>encorafenib,<br/>ibrutinib,<br/>ivosidenib,<br/>neratinib,<br/>nilotinib,<br/>venetoclax,<br/>vinblastine,<br/>vincristine</td><td>↑ anticancer drug</td><td>Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib.<br/>Co-administration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects.<br/>For further information, refer to the individual product label for anticancer drug.</td></tr><tr><td>Anticoagulants</td><td>warfarin<br/>rivaroxaban<br/>dabigatran<sup>a</sup><br/>apixaban</td><td>↑↓ warfarin<br/>↑ rivaroxaban<br/>↑ dabigatran<br/>↑ apixaban</td><td>Closely monitor INR if co-administration with warfarin is necessary.<br/>Increased bleeding risk with rivaroxaban. Avoid concomitant use.<br/>Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information.<br/>Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for co-administration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information.</td></tr><tr><td>Anticonvulsants</td><td>carbamazepine<sup>a</sup>,<br/>phenobarbital,<br/>phenytoin,<br/>primidone</td><td>↓ nirmatrelvir/ritonavir</td><td>Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</td></tr><tr><td>Anticonvulsants</td><td>clonazepam</td><td>↑ anticonvulsant</td><td>A dose decrease may be needed for clonazepam when co-administered with PAXLOVID and clinical monitoring is recommended.</td></tr><tr><td>Antidepressants</td><td>bupropion<br/>trazodone</td><td>↓ bupropion and active metabolite hydroxy-bupropion<br/>↑ trazodone</td><td>Monitor for an adequate clinical response to bupropion.<br/>Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following co-administration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to the trazadone product label for further information.</td></tr><tr><td>Antifungals</td><td>voriconazole<br/>ketoconazole,<br/>isavuconazonium sulfate,<br/>itraconazole<sup>a</sup></td><td>↓ voriconazole<br/>↑ ketoconazole<br/>↑ isavuconazonium sulfate<br/>↑ itraconazole<br/>↑ nirmatrelvir/ritonavir</td><td>Avoid concomitant use of voriconazole.<br/>Refer to the ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information.</td></tr><tr><td>Anti-gout</td><td>colchicine</td><td>↑ colchicine</td><td>Co-administration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see section 4.3).</td></tr><tr><td>Anti-HIV protease inhibitors</td><td>atazanavir,<br/>darunavir,<br/>tipranavir</td><td>↑ protease inhibitor</td><td>For further information, refer to the respective protease inhibitors’ product labels.<br/>Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events (see section 4.2).</td></tr><tr><td>Anti-HIV</td><td>efavirenz,<br/>maraviroc,<br/>nevirapine,<br/>zidovudine,<br/>bictegravir/ emtricitabine/ tenofovir</td><td>↑ efavirenz<br/>↑ maraviroc<br/>↑ nevirapine<br/>↓ zidovudine<br/>↑ bictegravir<br/>↔ emtricitabine<br/>↑ tenofovir</td><td>For further information, refer to the respective anti-HIV drugs’ product label.</td></tr><tr><td>Anti-infective</td><td>clarithromycin,<br/>erythromycin</td><td>↑ clarithromycin<br/>↑ erythromycin</td><td>Refer to the respective product label for anti-infective dose adjustment.</td></tr><tr><td>Antimycobacterial</td><td>rifampin,<br/>rifapentine</td><td>↓ nirmatrelvir/ritonavir</td><td>Co-administration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered (see section 4.3).</td></tr><tr><td>Antimycobacterial</td><td>bedaquiline<br/>rifabutin</td><td>↑ bedaquiline<br/>↑ rifabutin</td><td>Refer to the bedaquiline product label for further information.<br/>Refer to the rifabutin product label for further information on rifabutin dose reduction.</td></tr><tr><td>Antiparasitic agent</td><td>albendazole</td><td>↓ albendazole</td><td>Significant decreases in plasma concentrations of albendazole and its active metabolite may occur due to induction by ritonavir, with a risk of decreased albendazole efficacy. Clinical monitoring of therapeutic response and possible adjustment of albendazole dosage during treatment with PAXLOVID and following discontinuation is recommended.</td></tr><tr><td>Antipsychotics</td><td>lurasidone,<br/>pimozide</td><td>↑ lurasidone<br/>↑ pimozide</td><td>Co-administration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias (see section 4.3).</td></tr><tr><td>Antipsychotics</td><td>quetiapine<br/>clozapine</td><td>↑ quetiapine<br/>↑ clozapine</td><td>If co-administration is necessary, reduce quetiapine dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine product label for recommendations.<br/>If co-administration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.</td></tr><tr><td>Benign prostatic hyperplasia agents</td><td>silodosin</td><td>↑ silodosin</td><td>Co-administration contraindicated due to potential for postural hypotension (see section 4.3).</td></tr><tr><td>Calcium channel blockers</td><td>amlodipine,<br/>diltiazem,<br/>felodipine,<br/>nicardipine,<br/>nifedipine,<br/>verapamil</td><td>↑ calcium channel blocker</td><td>Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with PAXLOVID.<br/>If co-administered, refer to the individual product label for calcium channel blocker for further information.</td></tr><tr><td>Cardiac glycosides</td><td>digoxin</td><td>↑ digoxin</td><td>Caution should be exercised when co-administering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels.<br/>Refer to the digoxin product label for further information.</td></tr><tr><td>Cardiovascular agents</td><td>eplerenone<br/>ivabradine</td><td>↑ eplerenone<br/>↑ ivabradine</td><td>Co-administration with eplerenone is contraindicated due to potential for hyperkalemia (see section 4.3).<br/>Co-administration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances (see section 4.3).</td></tr><tr><td>Cardiovascular agents</td><td>aliskiren,<br/>ticagrelor,<br/>vorapaxar<br/>clopidogrel<br/>cilostazol<br/>mavacamten</td><td>↑ aliskiren<br/>↑ ticagrelor<br/>↑ vorapaxar<br/>↓ clopidogrel active metabolite<br/>↑ cilostazol<br/>↑ mavacamten</td><td>Avoid concomitant use with PAXLOVID.<br/>Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information.<br/>Co-administration with mavacamten may increase mavacamten plasma concentration and increase the risk of heart failure. Discontinue mavacamten for the duration of PAXLOVID treatment. Resumption of mavacamten within 5 days of completing PAXLOVID may result in higher exposure of mavacamten. Refer to the mavacamten product label for more information.</td></tr><tr><td>Corticosteroids primarily metabolized by CYP3A</td><td>betamethasone,<br/>budesonide,<br/>ciclesonide,<br/>dexamethasone,<br/>fluticasone,<br/>methylprednisolone,<br/>mometasone,<br/>triamcinolone</td><td>↑ corticosteroid</td><td>Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A4 inhibitor is low.<br/>Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.</td></tr><tr><td>Cystic fibrosis transmembrane conductance regulator potentiators</td><td>lumacaftor/ivacaftor</td><td>↓ nirmatrelvir/ritonavir</td><td>Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</td></tr><tr><td>Cystic fibrosis transmembrane conductance regulator potentiators</td><td>ivacaftor<br/>elexacaftor/ tezacaftor/ivacaftor<br/>tezacaftor/ivacaftor</td><td>↑ ivacaftor<br/>↑ elexacaftor/ tezacaftor/ivacaftor<br/>↑ tezacaftor/ivacaftor</td><td>Reduce dosage when co-administered with PAXLOVID. Refer to the individual product labels for more information.</td></tr><tr><td>Dipeptidyl peptidase 4 (DPP4) inhibitors</td><td>saxagliptin</td><td>↑ saxagliptin</td><td>Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information.</td></tr><tr><td>Endothelin receptor antagonists</td><td>bosentan</td><td>↑ bosentan</td><td>Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID.<br/>Refer to the bosentan product label for further information.</td></tr><tr><td>Ergot derivatives</td><td>dihydroergotamine,<br/>ergotamine,<br/>methylergonovine</td><td>↑ dihydroergotamine<br/>↑ ergotamine<br/>↑ methylergonovine</td><td>Co-administration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see section 4.3).</td></tr><tr><td>Hepatitis C direct acting antivirals</td><td>elbasvir/grazoprevir,<br/>glecaprevir/ pibrentasvir<br/>ombitasvir/ paritaprevir/ritonavir and dasabuvir<br/>sofosbuvir/ velpatasvir/ voxilaprevir</td><td>↑ antiviral</td><td>Increased grazoprevir concentrations can result in ALT elevations.<br/>Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID.<br/>Refer to the ombitasvir/paritaprevir/ ritonavir and dasabuvir label for further information.<br/>Refer to the sofosbuvir/velpatasvir/ voxilaprevir product label for further information.<br/>Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use (see section 4.2)<i>.</i></td></tr><tr><td>Herbal products</td><td>St. John’s Wort (<i>Hypericum perforatum</i>)</td><td>↓ nirmatrelvir/ritonavir</td><td>Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</td></tr><tr><td>HMG-CoA reductase inhibitors</td><td>lovastatin,<br/>simvastatin</td><td>↑ lovastatin<br/>↑ simvastatin</td><td>Co-administration contraindicated due to potential for myopathy including rhabdomyolysis (see section 4.3).<br/>Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment and for 5 days after completing PAXLOVID.</td></tr><tr><td>HMG-CoA reductase inhibitors</td><td>atorvastatin,<br/>rosuvastatin<sup>a</sup></td><td>↑ atorvastatin<br/>↑ rosuvastatin</td><td>Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be held prior to or after completing PAXLOVID.</td></tr><tr><td>Hormonal contraceptive</td><td>ethinyl estradiol</td><td>↓ ethinyl estradiol</td><td>An additional, non-hormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.</td></tr><tr><td>Immunosuppressants</td><td>voclosporin</td><td>↑ voclosporin</td><td>Co-administration contraindicated due to potential for acute and/or chronic nephrotoxicity (see section 4.3).</td></tr><tr><td>Immunosuppressants</td><td>Calcineurin inhibitors:<br/>cyclosporine,<br/>tacrolimus<br/>mTOR inhibitors:<br/>everolimus,<br/>sirolimus</td><td>↑ cyclosporine<br/>↑ tacrolimus<br/>↑ everolimus<br/>↑ sirolimus</td><td>Avoid concomitant use of calcineurin inhibitors and mTOR inhibitors during treatment with PAXLOVID.<br/>If the co-administration cannot be avoided, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and immunosuppressant-associated adverse reactions are recommended during and after treatment with PAXLOVID. Refer to the individual immunosuppressant product label and latest guidelines for further information and obtain expert consultation of a multidisciplinary group (see section 4.4).</td></tr><tr><td>Janus kinase (JAK) inhibitors</td><td>tofacitinib<br/>upadacitinib</td><td>↑ tofacitinib<br/>↑ upadacitinib</td><td>Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information.<br/>Dosing recommendations for co‑administration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information.</td></tr><tr><td>Long-acting beta-adrenoceptor agonist</td><td>salmeterol</td><td>↑ salmeterol</td><td>Avoid concomitant use with PAXLOVID. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.</td></tr><tr><td>Microsomal triglyceride transfer protein (MTTP) inhibitor</td><td>lomitapide</td><td>↑ lomitapide</td><td>Co-administration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions (see section 4.3).</td></tr><tr><td>Migraine medications</td><td>eletriptan<br/>ubrogepant</td><td>↑ eletriptan<br/>↑ ubrogepant</td><td>Co-administration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events (see section 4.3).<br/>Co-administration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions (see section 4.3).</td></tr><tr><td>Migraine medications</td><td>rimegepant</td><td>↑ rimegepant</td><td>Avoid concomitant use with PAXLOVID.</td></tr><tr><td>Mineralocorticoid receptor antagonists</td><td>finerenone</td><td>↑ finerenone</td><td>Co-administration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia (see section 4.3).</td></tr><tr><td>Muscarinic receptor antagonists</td><td>darifenacin</td><td>↑ darifenacin</td><td>The darifenacin daily dose should not exceed 7.5 mg when co-administered with PAXLOVID. Refer to the darifenacin product label for more information.</td></tr><tr><td>Narcotic analgesics</td><td>fentanyl,<br/>hydrocodone,<br/>oxycodone,<br/>meperidine<br/>methadone</td><td>↑ fentanyl<br/>↑ hydrocodone<br/>↑ oxycodone<br/>↑ meperidine<br/>↓ methadone</td><td>Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. Refer to the individual product label for more information.<br/>Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.</td></tr><tr><td>Neuropsychiatric agents</td><td>suvorexant<br/>aripiprazole,<br/>brexpiprazole,<br/>cariprazine,<br/>iloperidone,<br/>lumateperone,<br/>pimavanserin</td><td>↑ suvorexant<br/>↑ aripiprazole<br/>↑ brexpiprazole<br/>↑ cariprazine<br/>↑ iloperidone<br/>↑ lumateperone<br/>↑ pimavanserin</td><td>Avoid concomitant use of suvorexant with PAXLOVID.<br/>Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to the individual product label for more information.</td></tr><tr><td>Non-opioid analgesic (selective blocker of Na<sub>v</sub>1.8 sodium channels)</td><td>suzetrigine</td><td>↑ suzetrigine and active metabolite M6-SUZ</td><td>Co-administration contraindicated due to potential for serious and/or life-threatening suzetrigine adverse reactions (see section 4.3).</td></tr><tr><td>Pulmonary hypertension agents (PDE5 inhibitors)</td><td>sildenafil</td><td>↑ sildenafil</td><td>Co-administration of sildenafil with PAXLOVID is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope (see section 4.3).</td></tr><tr><td>Pulmonary hypertension agents<br/>(PDE5 inhibitors)<br/>Pulmonary hypertension agents<br/>(sGC stimulators)</td><td>tadalafil<br/>riociguat</td><td>↑ tadalafil<br/>↑ riociguat</td><td>Avoid concomitant use of tadalafil with PAXLOVID.<br/>Dosage adjustment is recommended for riociguat. Refer to the riociguat product label for more information.</td></tr><tr><td>Erectile dysfunction agents (PDE5 inhibitors)</td><td>avanafil<br/>sildenafil,<br/>tadalafil,<br/>vardenafil</td><td>↑ avanafil<br/>↑ sildenafil<br/>↑ tadalafil<br/>↑ vardenafil</td><td>Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established.<br/>Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID. Refer to the individual product label for more information.</td></tr><tr><td>Opioid antagonists</td><td>naloxegol</td><td>↑ naloxegol</td><td>Co-administration contraindicated due to the potential for opioid withdrawal symptoms (see section 4.3).</td></tr><tr><td>Sedative/hypnotics</td><td>triazolam,<br/>oral midazolam<sup>a</sup></td><td>↑ triazolam<br/>↑ midazolam</td><td>Co-administration contraindicated due to potential for extreme sedation and respiratory depression (see section 4.3).</td></tr><tr><td>Sedative/hypnotics</td><td>buspirone,<br/>clorazepate,<br/>diazepam,<br/>estazolam,<br/>flurazepam,<br/>zolpidem<br/>midazolam (administered parenterally)</td><td>↑ sedative/hypnotic<br/>↑ midazolam</td><td>A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events is recommended.<br/>Co-administration of midazolam (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.<br/>Refer to the midazolam product label for further information.</td></tr><tr><td>Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist</td><td>flibanserin</td><td>↑ flibanserin</td><td>Co-administration contraindicated due to potential for hypotension, syncope, and CNS depression (see section 4.3).</td></tr><tr><td>Vasopressin receptor antagonists</td><td>tolvaptan</td><td>↑ tolvaptan</td><td>Co-administration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see section 4.3).</td></tr><tr><td colspan=\"4\">a.\tSee section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.</td></tr></tbody></table></div>"
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-int-01-alfuzosin"
},
{
"reference": "ClinicalUseDefinition/cud-int-02-tamsulosin"
},
{
"reference": "ClinicalUseDefinition/cud-int-03-ranolazine"
},
{
"reference": "ClinicalUseDefinition/cud-int-04-amiodarone-dronedarone-flecainide-propafenone-qu"
},
{
"reference": "ClinicalUseDefinition/cud-int-05-lidocaine-systemic-disopyramide"
},
{
"reference": "ClinicalUseDefinition/cud-int-06-apalutamide-enzalutamide"
},
{
"reference": "ClinicalUseDefinition/cud-int-07-abemaciclib-ceritinib-dasatinib-encorafenib-ibru"
},
{
"reference": "ClinicalUseDefinition/cud-int-08-warfarin-rivaroxaban-dabigatrana-apixaban"
}
]
},
{
"title": "4.6. Fertility, pregnancy and lactation",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.6",
"display": "4.6. Fertility, pregnancy and lactation"
}
]
},
"section": [
{
"title": "4.6.1. Women of childbearing potential/Contraception in males and females",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.6.1",
"display": "4.6.1. Women of childbearing potential/Contraception in males and females"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>There are limited human data on the use of PAXLOVID during pregnancy to inform the drug-associated risk of adverse developmental outcomes; women of childbearing potential should avoid becoming pregnant during treatment with PAXLOVID and for 7 days after completing PAXLOVID treatment.</p><p>Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment with PAXLOVID, and until one menstrual cycle after stopping PAXLOVID<sup> </sup>(see section 4.5).</p></div>"
}
},
{
"title": "4.6.2. Pregnancy",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.6.2",
"display": "4.6.2. Pregnancy"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>There are limited data from the use of PAXLOVID in pregnant women. PAXLOVID should be used during pregnancy only if the potential benefits outweigh the potential risks for the mother and the fetus.</p><p>Animal data with nirmatrelvir have shown developmental toxicity in the rabbit (lower fetal body weights) but not in the rat. There was no nirmatrelvir-related effect on fetal morphology or embryo-fetal viability at any dose tested in rat or rabbit embryo-fetal developmental toxicity studies. There were no nirmatrelvir-related adverse effects in a pre- and postnatal developmental study in rats (see section 5.3).</p><p>A large number (6,100 live births) of pregnant women were exposed to ritonavir during pregnancy; of these, 2,800 live births were exposed during the first trimester. These data largely refer to exposures where ritonavir was used in combination therapy and not at therapeutic ritonavir doses but at lower doses as a PK enhancer for other protease inhibitors, similar to the ritonavir dose used for nirmatrelvir/ritonavir. These data indicate no increase in the rate of birth defects compared to rates observed in population-based birth defect surveillance systems.</p><p>Animal data with ritonavir have shown reproductive toxicity (see section 5.3).</p></div>"
}
},
{
"title": "4.6.3. Breast-feeding",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.6.3",
"display": "4.6.3. Breast-feeding"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>In a clinical pharmacokinetics study, 8 healthy lactating women who were at least 12 weeks postpartum were administered 3 doses (steady-state dosing) of 300 mg/100 mg nirmatrelvir/ritonavir. Nirmatrelvir and ritonavir were excreted in breast milk in small amounts, with a milk to plasma AUC ratio of 0.26 and 0.07, respectively. The estimated daily infant dose (assuming average milk consumption of 150 mL/kg/day), was 1.8% and 0.2% of the maternal dose.</p><p>There are no available data on the effects of nirmatrelvir or ritonavir on the breast-fed newborn/infant or on milk production. A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment with PAXLOVID and for 48 hours after completing PAXLOVID treatment.</p></div>"
}
},
{
"title": "4.6.4. Fertility",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.6.4",
"display": "4.6.4. Fertility"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>There are no human data on the effect of PAXLOVID on fertility. No human data on the effect of nirmatrelvir on fertility are available. Nirmatrelvir produced no effects on fertility in rats (see section 5.3).</p><p>There are no human data on the effect of ritonavir on fertility. Ritonavir produced no effects on fertility in rats.</p></div>"
}
}
]
},
{
"title": "4.7. Effects on ability to drive and use machines",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.7",
"display": "4.7. Effects on ability to drive and use machines"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>There are no clinical studies that evaluated the effects of PAXLOVID on ability to drive and use machines.</p></div>"
}
},
{
"title": "4.8. Undesirable effects",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.8",
"display": "4.8. Undesirable effects"
}
]
},
"entry": [
{
"reference": "ClinicalUseDefinition/cud-ae-01-hypersensitivity"
},
{
"reference": "ClinicalUseDefinition/cud-ae-02-anaphylaxis"
},
{
"reference": "ClinicalUseDefinition/cud-ae-03-dysgeusiaa-headache"
},
{
"reference": "ClinicalUseDefinition/cud-ae-04-hypertension"
},
{
"reference": "ClinicalUseDefinition/cud-ae-05-diarrheaa-nausea"
},
{
"reference": "ClinicalUseDefinition/cud-ae-06-vomitinga-abdominal-pain"
}
],
"section": [
{
"title": "4.8.1. Summary of the safety profile",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.8.1",
"display": "4.8.1. Summary of the safety profile"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The safety of PAXLOVID was based on data from three Phase 2/3 randomized, placebo-controlled trials in adult participants 18 years of age and older (see section 5.1):</p><p>Study C4671005 (EPIC-HR) and Study C4671002 (EPIC-SR) investigated PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) every 12 hours for 5 days in symptomatic participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Participants were to present with mild-to-moderate COVID-19 at baseline.</p><p>Study C4671006 (EPIC<i>-</i>PEP) investigated PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) every 12 hours for 5 or 10 days in asymptomatic household contact of individuals with a recent diagnosis of SARS-CoV-2 infection. Participants were to have a negative SARS-CoV-2 result at baseline.</p><p>Across the three studies, 3,515 participants received a dose of PAXLOVID and 2,585 participants received a dose of placebo. The most common adverse reactions (≥1% incidence in the PAXLOVID group and occurring at a greater frequency than in the placebo group) were dysgeusia (5.9% and 0.4%, respectively) and diarrhea (2.9% and 1.9%, respectively).</p><p>The safety profile of PAXLOVID in participants with severe renal impairment, including those requiring hemodialysis, was consistent with the safety profile observed in the placebo-controlled trials.</p></div>"
}
},
{
"title": "4.8.2. Tabulated summary of adverse drug reactions (ADRs)",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.8.2",
"display": "4.8.2. Tabulated summary of adverse drug reactions (ADRs)"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The adverse drug reactions in Table 3 are listed below by system organ class.</p><p><b>Table </b><b>3</b><b>:</b><b>\tAdverse drug reactions (ADRs) by system organ class and council for international organizations of medical sciences (CIOMS) frequency category listed in order of decreasing medical seriousness or clinical importance within each frequency category and SOC</b></p><table><thead><tr><th><b>System Organ Class</b></th><th><b>Very Common</b><br/><b>≥1/10</b></th><th><b>Common</b><br/><b>≥1/100 to <1/10</b></th><th><b>Uncommon</b><br/><b>≥1/1,000 to <1/100</b></th><th><b>Rare</b><br/><b>≥1/10,000 to <1/1,000</b></th><th><b>Very Rare</b><br/><b><1/10,000</b></th><th><b>Frequency Not Known</b><br/><b>(cannot be estimated from the available data)</b></th></tr></thead><tbody><tr><td>Immune system disorders</td><td/><td/><td>Hypersensitivity*</td><td>Anaphylaxis*</td><td/><td/></tr><tr><td>Nervous system disorders</td><td/><td>Dysgeusia<sup>a</sup><br/>Headache<sup>a</sup></td><td/><td/><td/><td/></tr><tr><td>Vascular disorders</td><td/><td/><td>Hypertension*</td><td/><td/><td/></tr><tr><td>Gastrointestinal disorders</td><td/><td>Diarrhea<sup>a</sup><br/>Nausea*</td><td>Vomiting<sup>a</sup><br/>Abdominal pain*</td><td/><td/><td/></tr><tr><td>Skin and subcutaneous tissue disorders</td><td/><td/><td/><td>Toxic epidermal necrolysis*<br/>Stevens-Johnson syndrome*</td><td/><td/></tr><tr><td>General disorders and administration site conditions</td><td/><td/><td/><td>Malaise*</td><td/><td/></tr><tr><td colspan=\"7\">*\tAdverse drug reaction (ADR) identified post-marketing.<br/>a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment.</td></tr></tbody></table></div>"
}
}
]
},
{
"title": "4.9. Overdose",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "4.9",
"display": "4.9. Overdose"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Treatment of overdose with PAXLOVID should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with PAXLOVID.</p></div>"
}
}
]
},
{
"title": "5. PHARMACOLOGICAL PROPERTIES",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5",
"display": "5. PHARMACOLOGICAL PROPERTIES"
}
]
},
"section": [
{
"title": "5.1. Pharmacodynamic properties",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1",
"display": "5.1. Pharmacodynamic properties"
}
]
},
"section": [
{
"title": "5.1.1. Mechanism of action",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.1",
"display": "5.1.1. Mechanism of action"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (M<sup>pro</sup>), also referred to as 3C-like protease (3CL<sup>pro</sup>) or nsp5 protease. Inhibition of the SARS-CoV-2 M<sup>pro</sup> renders the protein incapable of processing polyprotein precursors which leads to the prevention of viral replication.</p><p>Ritonavir is not active against SARS-CoV-2 M<sup>pro</sup>. Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, thereby providing increased plasma concentrations of nirmatrelvir.</p></div>"
}
},
{
"title": "5.1.2. Antiviral activity",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.2",
"display": "5.1.2. Antiviral activity"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>In vitro antiviral activity</i></p><p>Nirmatrelvir exhibited antiviral activity against SARS-CoV-2 infection of differentiated normal human bronchial epithelial (dNHBE) cells, a primary human lung alveolar epithelial cell line (EC<sub>50</sub> value of 61.8 nM and EC<sub>90</sub> value of 181 nM) after 3 days of drug exposure.</p><p>The antiviral activity of nirmatrelvir against the Omicron sub-variants BA.2, BA.2.12.1, BA.4, BA.4.6, BA.5, BF.7 (P252L+F294L), BF.7 (T243I), BQ.1.11, BQ.1, XBB.1.5, EG.5, and JN.1 was assessed in Vero E6-TMPRSS2 cells in the presence of a P-gp inhibitor. Nirmatrelvir had a median EC<sub>50</sub> value of 88 nM (range: 39-146 nM) against the Omicron sub-variants, reflecting EC<sub>50</sub> value fold changes ≤1.8 relative to the USA-WA1/2020 isolate.</p><p>In addition, the antiviral activity of nirmatrelvir against the SARS-CoV-2 Alpha, Beta, Gamma, Delta, Lambda, Mu, and Omicron BA.1 variants was assessed in Vero E6 P-gp knockout cells. Nirmatrelvir had a median EC<sub>50</sub> value of 25 nM (range: 16-141 nM). The Beta variant was the least susceptible variant tested, with an EC<sub>50</sub> value fold-change of 3.7 relative to USA-WA1/2020. The other variants had EC<sub>50</sub> value fold-changes ≤1.1 relative to USA-WA1/2020.</p></div>"
}
},
{
"title": "5.1.3. Antiviral resistance in cell culture and biochemical assays",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.3",
"display": "5.1.3. Antiviral resistance in cell culture and biochemical assays"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>SARS-CoV-2 M<sup>pro</sup> residues potentially associated with nirmatrelvir resistance have been identified using a variety of methods, including SARS-CoV-2 resistance selection, testing of recombinant SARS-CoV-2 viruses with M<sup>pro</sup> substitutions, and biochemical assays with recombinant SARS-CoV-2 M<sup>pro</sup> containing amino acid substitutions. Table 4 indicates M<sup>pro</sup> substitutions and combinations of M<sup>pro</sup> substitutions that have been observed in nirmatrelvir-selected SARS-CoV-2 in cell culture. Individual M<sup>pro</sup> substitutions are listed regardless of whether they occurred alone or in combination with other M<sup>pro</sup> substitutions. Note that the M<sup>pro</sup> S301P and T304I substitutions overlap the P6 and P3 positions of the nsp5/nsp6 cleavage site located at the C-terminus of M<sup>pro</sup>. Substitutions at other M<sup>pro</sup> cleavage sites have not been associated with nirmatrelvir resistance in cell culture. The clinical significance of these substitutions is unknown.</p><p><b>Table </b><b>4</b><b>:</b><b>\tSARS-CoV-2 </b><b>M</b><b><sup>pro</sup></b><b> amino acid substitutions selected by nirmatrelvir in cell culture</b></p><table><thead><tr><th>Single substitution<br/>(EC<sub>50</sub> value fold change)</th><th>T21I (1.1-4.8), L50F (1.5-4.2), P108S (ND), T135I (ND), F140L (4.1), S144A (2.2-5.3), C160F (ND), E166A (3.3), E166V (25-288), L167F (ND), T169I (ND), H172Y (ND), A173V (0.9-1.7), V186A (ND), R188G (ND), A191V (ND), A193P (ND), P252L (5.9), S301P (ND), and T304I (1.4-5.5).</th></tr></thead><tbody><tr><td>≥2 substitutions<br/>(EC<sub>50</sub> value fold change)</td><td>T21I+S144A (9.4), T21I+E166V (83), T21I+A173V (3.1-8.9), T21I+T304I (3.0-7.9), L50F+E166V (34-175), L50F+T304I (5.9), T135I+T304I (3.8), F140L+A173V (10.1), H172Y+P252L (ND), A173V+T304I (20.2), T21I+L50F+A193P+S301P (28.8), T21I+S144A+T304I (27.8), T21I+C160F+A173V+V186A+T304I (28.5), T21I+A173V+T304I (15), and L50F+F140L+L167F+T304I (54.7).</td></tr><tr><td colspan=\"2\">Abbreviations: ND=no data (substitution emerged from nirmatrelvir resistance selection but has not been tested for EC<sub>50</sub> determination in an antiviral assay).</td></tr></tbody></table><p>In a biochemical assay using recombinant SARS-CoV-2 M<sup>pro</sup> containing amino acid substitutions, the following SARS-CoV-2 M<sup>pro</sup> substitutions led to ≥3-fold reduced activity (fold-change based on Ki values) of nirmatrelvir: Y54A (25), F140A (21), F140L (7.6), F140S (230), G143S (3.6), S144A (46), S144E (480), S144T (170), H164N (6.7), E166A (35), E166G (6.2), E166V (7,700), P168del (9.3), H172Y (250), A173S (4.1), A173V (16), R188G (38), Q192L (29), Q192P (7.8), and V297A (3.0). In addition, the following combinations of M<sup>pro</sup> substitutions led to ≥3-fold reduced nirmatrelvir activity: T21I+S144A (20), T21I+E166V (11,000), T21I+A173V (15), L50F+E166V (4,500), E55L+S144A (56), T135I+T304I (5.1), F140L+A173V (95), S144A+T304I (28), E166V+L232R (5,700), P168del+A173V (170), H172Y+P252L (180), A173V+T304I (28), T21I+S144A+T304I (51), T21I+A173V+T304I (55), L50F+E166A+L167F (180), T21I+L50F+A193P+S301P (7.3), L50F+F140L+L167F+T304I (190), and T21I+C160F+A173V+V186A+T304I (28). The following substitutions and substitution combinations emerged in cell culture but conferred <3- fold reduced nirmatrelvir activity in biochemical assays: T21I (1.6), L50F (0.2), P108S (2.9), T135I (2.2), C160F (0.6), L167F (1.5), T169I (1.4), V186A (0.8), A191V (0.8), A193P (0.9), P252L (0.9), S301P (0.2), T304I (1.0), T21I+T304I (1.8), and L50F+T304I (1.3). The clinical significance of these substitutions is unknown.</p><p>Most single and some double M<sup>pro</sup> amino acid substitutions identified which reduced the susceptibility of SARS-CoV-2 to nirmatrelvir resulted in an EC<sub>50</sub> shift of <5-fold compared to wild type SARS-CoV-2 in an antiviral cell assay. Virus containing E166V shows the greatest reduction in susceptibility to nirmatrelvir and appears to have replication defect since it either could not be generated or had a very low virus titer. In general, triple and some double M<sup>pro</sup> amino acid substitutions led to EC<sub>50</sub> changes of >5-fold to that of wild type. The clinical significance needs to be further understood, particularly in the context of nirmatrelvir high clinical exposure (≥5× EC<sub>90</sub>). Thus far, these substitutions have not been identified as treatment-emergent substitutions associated with hospitalization or death from the EPIC-HR or EPIC-SR studies.</p><p>Treatment-emergent substitutions were evaluated among participants in clinical trials EPIC-HR/SR with sequence data available at both baseline and a post-baseline visit (n=907 PAXLOVID-treated participants, n=946 placebo-treated participants). SARS-CoV-2 M<sup>pro</sup> amino acid changes were classified as PAXLOVID treatment emergent substitutions if they were absent at baseline, occurred at the same amino acid position in 3 or more PAXLOVID-treated participants and were ≥2.5-fold more common in PAXLOVID-treated participants than placebo-treated participants post-dose. The following PAXLOVID treatment-emergent M<sup>pro</sup> substitutions were observed: T98I/R/del (n=4), E166V (n=3), and W207L/R/del (n=4). Within the M<sup>pro</sup> cleavage sites, the following PAXLOVID treatment-emergent substitutions were observed: A5328S/V (n=7) and S6799A/P/Y (n=4). These cleavage site substitutions were not associated with the co-occurrence of any specific M<sup>pro</sup> substitutions.</p><p>None of the treatment-emergent substitutions listed above in M<sup>pro</sup> or M<sup>pro</sup> cleavage sites occurred in PAXLOVID-treated participants who experienced hospitalization. Thus, the clinical significance of these substitutions is unknown.</p></div>"
}
},
{
"title": "5.1.4. Viral load rebound",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.4",
"display": "5.1.4. Viral load rebound"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Post-treatment increases in SARS-CoV-2 nasal RNA levels (i.e., viral RNA rebound) were observed on Day 10 and/or Day 14 after initiating study treatment in a subset of PAXLOVID and placebo recipients in EPIC-HR and EPIC-SR, irrespective of COVID-19 symptoms. The frequency of detection of post-treatment nasal viral RNA rebound varied according to analysis parameters but was generally similar among PAXLOVID and placebo recipients. A similar or smaller percentage of placebo recipients compared to PAXLOVID recipients had nasal viral RNA results < lower limit of quantitation (LLOQ) at all study timepoints in both the treatment and post-treatment periods.</p><p>Post-treatment viral RNA rebound was not associated with the primary clinical outcome of COVID-19-related hospitalization or death from any cause through Day 28 following the single 5-day course of PAXLOVID treatment. The clinical relevance of post-treatment increases in viral RNA following PAXLOVID or placebo treatment is unknown.</p><p>EPIC-HR and EPIC-SR were not designed to evaluate symptomatic viral RNA rebound, and most episodes of symptom rebound occurred after Day 14 (the last day SARS-CoV-2 RNA levels were routinely assessed). The frequency of symptom rebound through Day 28, irrespective of viral RNA results, was similar among PAXLOVID and placebo recipients.</p></div>"
}
},
{
"title": "5.1.5. Cross-resistance",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.5",
"display": "5.1.5. Cross-resistance"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Cross-resistance is not expected between nirmatrelvir and remdesivir or any other anti-SARS-CoV-2 agents with different mechanisms of action (i.e., agents that are not M<sup>pro</sup> inhibitors).</p></div>"
}
},
{
"title": "5.1.6. Pharmacodynamic effects",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.6",
"display": "5.1.6. Pharmacodynamic effects"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Cardiac electrophysiology</i></p><p>At 3 times the steady-state peak plasma concentration (C<sub>max</sub>) at the recommended dose, nirmatrelvir does not prolong the QTc interval to any clinically relevant extent.</p><p><i>Effects on viral RNA levels</i></p><p>Changes from baseline relative to placebo at Day 5 in viral RNA levels in nasopharyngeal samples are summarized by study in Table 5.</p><p><b>Table </b><b>5</b><b>:</b>\t<b>Analysis of change from baseline to Day 5 in log</b><b><sub>10</sub></b><b> (viral RNA levels, copies/mL)</b><b>; EPIC-HR and EPIC-SR (mITT1 analysis set)</b></p><table><thead><tr><th/><th colspan=\"2\"><b>EPIC-HR (mITT1</b><b><sup>a</sup></b><b>)</b></th><th colspan=\"2\"><b>EPIC-SR (mITT1</b><b><sup>b</sup></b><b>)</b></th></tr></thead><tbody><tr><td/><td><b>PAXLOVID</b></td><td><b>Placebo</b></td><td><b>PAXLOVID</b></td><td><b>Placebo</b></td></tr><tr><td><b>Primary VoC</b><b><sup>c</sup></b></td><td colspan=\"2\">Delta (99%)</td><td colspan=\"2\">Delta (79%)<br/>Omicron (19%)</td></tr><tr><td><b>Baseline</b></td><td>n=764</td><td>n=784</td><td>n=542</td><td>n=514</td></tr><tr><td>Median</td><td>6.075</td><td>5.990</td><td>6.615</td><td>6.430</td></tr><tr><td>Mean (SD)</td><td>5.780<br/>(2.077)</td><td>5.617<br/>(2.143)</td><td>6.214<br/>(1.794)</td><td>6.045<br/>(1.862)</td></tr><tr><td><b>Day 5</b></td><td>n=676</td><td>n=683</td><td>n=498</td><td>n=473</td></tr><tr><td>Median change from baseline</td><td>-2.990</td><td>-2.160</td><td>-3.680</td><td>-2.630</td></tr><tr><td>Median reduction relative to placebo</td><td>-0.830</td><td/><td>-1.050</td><td/></tr><tr><td>Adjusted change from baseline,\nmean (95% CI)</td><td>-3.087<br/>(-3.219,\n-2.955)</td><td>-2.310<br/>(-2.439,\n-2.180)</td><td>-3.419<br/>(-3.584,\n-3.253)</td><td>-2.551<br/>(-2.723,\n-2.378)</td></tr><tr><td>Mean reduction relative to placebo,\nmean (95% CI)</td><td>-0.777<br/>(-0.937,\n-0.617)</td><td/><td>-0.868<br/>(-1.073,\n-0.663)</td><td/></tr><tr><td>p-value</td><td><0.0001</td><td/><td><0.0001</td><td/></tr><tr><td colspan=\"5\">Abbreviations: CI=confidence interval; COVID-19=Coronavirus Disease 2019; mAb=monoclonal antibody; mITT=modified intent-to-treat; RT-PCR=reverse transcriptase–polymerase chain reaction; SD=standard deviation; VoC=variant of concern.<br/>a.\tAll treated participants with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment.<br/>b.\tAll treated participants with at least 1 post-baseline visit through Day 28; 57% of these participants were vaccinated against COVID-19 at baseline.<br/>c.\tVoC lineage percentage relates to the entire study populations for EPIC-HR and EPIC-SR.</td></tr></tbody></table><p>The degree of reduction in viral RNA levels relative to placebo following 5 days of PAXLOVID treatment was similar between unvaccinated high-risk subjects in EPIC-HR and vaccinated high-risk subjects in EPIC-SR.</p><p><i>Effect on lipids</i></p><p>The changes in lipids in nirmatrelvir/ritonavir treated group were not statistically different than placebo/ritonavir treated group in an exploratory analysis of lipids in multiple ascending dose cohorts in which healthy participants were randomized to receive either escalating doses (75, 250 and 500 mg) of nirmatrelvir (n=4 per cohort) or placebo (n=2 per cohort), enhanced with ritonavir 100 mg, twice a day for 10 days.</p><p>In participants receiving placebo/ritonavir twice a day, a modest increase in cholesterol (≤27.2 mg/dL), LDL cholesterol (≤23.2 mg/dL), triglycerides (≤64.3 mg/dL) and decrease in HDL cholesterol (≤4 mg/dL) was observed. The clinical significance of such changes with short-term treatment is unknown.</p></div>"
}
},
{
"title": "5.1.7. Clinical efficacy",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.1.7",
"display": "5.1.7. Clinical efficacy"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Efficacy in participants at high risk of progressing to severe COVID-19 illness (EPIC-HR)</i></p><p>The efficacy of PAXLOVID is based on the final analysis of EPIC-HR, a Phase 2/3, randomized, double-blind, placebo-controlled study in non-hospitalized symptomatic adult participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible participants were 18 years of age and older with at least 1 of the following risk factors for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or were 60 years of age and older regardless of comorbidities. Participants with COVID-19 symptom onset of ≤5 days were included in the study.</p><p>Participants were randomized (1:1) to receive PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) or placebo orally every 12 hours for 5 days. The study excluded individuals with a history of prior COVID-19 infection or vaccination. The primary efficacy endpoint was the proportion of participants with COVID-19 related hospitalization or death from any cause through Day 28. Time to sustained alleviation and sustained resolution of all targeted symptoms through Day 28 were key secondary efficacy endpoints. These analyses were conducted in the modified intent-to-treat (mITT) analysis set (all treated participants with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), the mITT1 analysis set (all treated participants with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated participants with onset of symptoms ≤5 days).</p><p>A total of 2,113 participants were randomized to receive either PAXLOVID or placebo. At baseline, mean age was 45 years; 51% were male; 71% were White, 4% were Black or African American, and 15% were Asian; 41% were Hispanic or Latino; 67% of participants had onset of symptoms ≤3 days before initiation of study treatment; 49% of participants were serological negative at baseline. The mean (SD) baseline viral load was 4.71 log<sub>10</sub> copies/mL (2.89); 27% of participants had a baseline viral load of ≥7 log<sub>10</sub> copies/mL; 6% of participants either received or were expected to receive COVID-19 therapeutic mAb treatment at the time of randomization and were excluded from the mITT and mITT1 analyses.</p><p>The baseline demographic and disease characteristics were balanced between the PAXLOVID and placebo groups.</p><p>The proportions of participants who discontinued treatment due to an adverse event were 2.0% in the PAXLOVID group and 4.3% in the placebo group.</p><p>Table 6 provides results of the primary endpoint in the mITT1 analysis population demonstrating superiority of PAXLOVID compared to placebo for COVID-19 related hospitalization or death from any cause through Day 28. For the primary endpoint, the relative risk reduction in the mITT1 analysis population for PAXLOVID compared to placebo was 86% (95% CI: 72%, 93%).</p><p><b>Table </b><b>6</b><b>:</b><b>\tEfficacy results in non-hospitalized adults with COVID-19 dosed within 5</b><b> </b><b>days of symptom onset who did not receive COVID-19 mAb treatment at baseline (mITT1 analysis set)</b></p><table><thead><tr><th/><th><b>PAXLOVID</b><br/><b>(N=977)</b></th><th><b>Placebo</b><br/><b>(N=989)</b></th></tr></thead><tbody><tr><td colspan=\"3\">COVID-19 related hospitalization or death from any cause through Day 28</td></tr><tr><td>n (%)</td><td>9 (0.9%)</td><td>64 (6.5%)</td></tr><tr><td/><td/><td/></tr><tr><td>Reduction relative to placebo<sup>a</sup> (95% CI), %</td><td>-5.64 (-7.31, -3.97)</td><td/></tr><tr><td>p-value</td><td><0.0001</td><td/></tr><tr><td>All-cause mortality through Day 28, %</td><td>0</td><td>12 (1.2%)</td></tr><tr><td colspan=\"3\">Abbreviations: CI=confidence interval; COVID-19=Coronavirus Disease 2019; mAb=monoclonal antibody; mITT1=modified intent-to-treat 1 (all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, with at least 1 post-baseline visit through Day 28, who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment and were treated ≤5 days after COVID-19 symptom onset).<br/>The determination of primary efficacy was based on a planned interim analysis of 754 participants in mITT population. The estimated risk reduction was -6.5% with a 95% CI of (-9.3%, -3.7%) and 2-sided p-value <0.0001.<br/>a.\tThe estimated cumulative proportion of participants hospitalized or death by Day 28 was calculated for each treatment group using the Kaplan-Meier method, where participants without hospitalization and death status through Day 28 were censored at the time of study discontinuation.</td></tr></tbody></table><p>Through Week 24, no deaths were reported in the PAXLOVID group compared with 15 deaths in the placebo group.</p><p>Consistent results were observed in the mITT and mITT2 analysis populations. A total of 1,318 participants were included in the mITT analysis population. The event rates of COVID-19 related hospitalization or death from any cause through Day 28 were 5/671 (0.75%) in the PAXLOVID group, and 44/647 (6.80%) in the placebo group.</p><p>Similar trends have been observed across subgroups of participants (see Figure 1).</p><p><b>Figure 1:</b><b>\tAdults with COVID-19 dosed within 5 days of symptom onset with COVID</b><b>-19</b><b>-related hospitalization or death from any cause through Day 28</b></p><p>Abbreviations: BMI=body mass index; COVID-19=Coronavirus Disease 2019; mAb=monoclonal antibody; mITT1=modified intent-to-treat 1 (all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, with at least 1 post-baseline visit through Day 28, who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment and were treated ≤5 days after COVID-19 symptom onset); N=number of participants in the category of the analysis set; SARS-COV-2=severe acute respiratory syndrome coronavirus 2.</p><p>All categories are based on mITT1 population except for COVID-19 mAb treatment which is based on mITT2 population.</p><p>Seropositivity was defined if results were positive in either Elecsys anti SARS-CoV-2 S or Elecsys SARS-CoV-2 (N) assay.</p><p>The difference of the proportions in the 2 treatment groups and its 95% confidence interval based on normal approximation of the data are presented.</p><p>Participants performed daily self-assessments of COVID-19 associated symptoms of cough, shortness of breath or difficulty breathing, feeling feverish, chills or shivering, muscle or body aches, diarrhea, nausea, vomiting, headache, sore throat, stuffy or runny nose. The severity of each symptom was rated as absent, mild, moderate, or severe. Sustained symptom alleviation was defined as the first of 4 consecutive days when all of the above symptoms scored as moderate or severe at study entry were scored as mild or absent, and all of the above symptoms scored mild or absent at study entry were scored as absent. Sustained symptom resolution was defined as the time when all of the above symptoms were scored as absent for 4 consecutive days. Table 7 displays the results for time to sustained symptom alleviation and sustained symptom resolution in the mITT1 population. The PAXLOVID group demonstrated superiority to the placebo group in both analyses.</p><p><b>Table </b><b>7</b><b>:</b><b>\t</b><b>Analyses of time to sustained symptom alleviation and sustained symptom resolution through 28 days (mITT1 analysis set): EPIC-HR</b></p><table><thead><tr><th/><th><b>PAXLOVID</b><br/><b>(N=970)</b></th><th><b>Placebo</b><br/><b>(N=986)</b></th></tr></thead><tbody><tr><td>Time to sustained symptom alleviation (days)<sup>a</sup><br/>Median<br/>HR vs placebo (95% CI)<sup>b</sup><br/>p-value</td><td>13<br/>1.266 (1.134, 1.412)<br/><0.0001</td><td>15</td></tr><tr><td>Time to sustained symptom resolution (days)<sup>a</sup><br/>Median<br/>HR vs placebo (95% CI)<sup>b</sup><br/>p-value</td><td>16<br/>1.200 (1.068, 1.348)<br/>0.0022</td><td>19</td></tr><tr><td colspan=\"3\">Abbreviations: CI=confidence interval; HR=hazard ratio; COVID-19=Coronavirus Disease 2019; mAb=monoclonal antibody; mITT1=modified intent-to-treat 1 (all participants randomly assigned to study intervention, who took at least 1 dose of study intervention, with at least 1 post-baseline visit through Day 28, who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment and were treated ≤5 days after COVID-19 symptom onset); SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.<br/>a.\tParticipants who were hospitalized for the treatment of COVID-19 or died during the 28-day period were considered as not achieving sustained symptom alleviation or resolution.<br/>b.\tEvaluation was done in a Cox proportional hazard model with treatment and geographic region effects as independent variables, and symptom onset duration (≤3, >3 days), baseline SARS-CoV-2 serology status and baseline viral load (<4, ≥4 log<sub>10</sub> copies/mL) as covariates.</td></tr></tbody></table><p>The proportion of participants with any severe COVID-19 associated symptom was 22% in the PAXLOVID group and 19% in the placebo group at baseline (Day 1), 17% and 18%, respectively, during treatment (from Day 2 to Day 6), and 8% and 11%, respectively, after treatment (from Day 7 to Day 28).</p><p><i>Efficacy in vaccinated participants with at least 1 risk factor for progression to severe COVID</i><i>-19 illness (EPIC-SR)</i></p><p>PAXLOVID is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19.</p><p>EPIC-SR was a Phase 2/3, randomized, double-blind, placebo-controlled study in non-hospitalized symptomatic adult participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Eligible participants were 18 years of age and older with COVID-19 symptom onset of ≤5 days who were at standard risk for progression to severe disease. The study included previously unvaccinated participants without risk factors or fully vaccinated participants with at least 1 of the risk factors for progression to severe disease (as defined in the EPIC-HR section above and by local regulations and practices). A total of 1,296 participants were randomized (1:1) to receive PAXLOVID<b> </b>or placebo orally every 12 hours for 5 days; of these, 49% were vaccinated at baseline with at least 1 risk factor for progression to severe disease.</p><p>The primary endpoint in this study, the difference in time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28 among PAXLOVID versus placebo recipients, was not met.</p><p>Analyses of efficacy presented below is based on an exploratory analysis of the subgroup of vaccinated participants with at least 1 risk factor for progression to severe disease. In vaccinated participants, Table 8 provides results of the proportion of participants with COVID-19 related hospitalization or death from any cause through Day 28 (secondary endpoint of EPIC-SR). The relative risk reduction in the mITT1 analysis population for PAXLOVID compared to placebo was 58%. The result did not reach statistical significance.</p><p><b>Table </b><b>8</b><b>:</b><b>\t</b><b>Efficacy results in non-hospitalized vaccinated adults with at least 1 risk factor for progression to severe COVID-19 who were dosed within 5 days of symptom onset (mITT1 analysis set)</b></p><table><thead><tr><th/><th><b>PAXLOVID</b><br/><b>(N=317)</b></th><th><b>Placebo</b><br/><b>(N=314)</b></th></tr></thead><tbody><tr><td colspan=\"3\">COVID-19 related hospitalization or death from any cause through Day 28</td></tr><tr><td>n (%)</td><td>3 (0.9%)</td><td>7 (2.2%)</td></tr><tr><td/><td/><td/></tr><tr><td>Reduction relative to placebo<sup>a</sup> (95% CI), %</td><td>-1.292 (-3.255, 0.671)</td><td/></tr><tr><td>All-cause mortality through Day 28, %</td><td>0</td><td>1 (0.3%)</td></tr><tr><td colspan=\"3\">Abbreviations: CI=confidence interval; COVID-19=Coronavirus Disease 2019; mITT1=modified intent-to-treat 1 (all participants randomly assigned to study intervention who took at least 1 dose of study intervention and with at least 1 post-baseline visit through Day 28).<br/>a.\tThe estimated cumulative proportion of participants hospitalized or death by Day 28 was calculated for each treatment group using the Kaplan-Meier method, where participants without hospitalization and death status through Day 28 were censored at the time of study discontinuation.</td></tr></tbody></table><p><i>Post-exposure prophylaxis (EPIC-PEP)</i></p><p>PAXLOVID is not indicated for the post-exposure prophylaxis of COVID-19.</p><p>EPIC-PEP was a Phase 2/3, randomized, double-blind, double-dummy, placebo-controlled study assessing the efficacy of PAXLOVID (administered 5 days or 10 days) in post-exposure prophylaxis of COVID-19 in household contacts of symptomatic individuals infected with SARS-CoV-2. Eligible participants were asymptomatic adults 18 years of age and older who were SARS-CoV-2 negative at screening and who lived in the same household with symptomatic individuals with a recent diagnosis of SARS-CoV-2. A total of 2,736 participants were randomized (1:1:1) to receive PAXLOVID orally every 12 hours for 5 days, PAXLOVID orally every 12 hours for 10 days, or placebo.</p><p>The primary endpoint in this study, the risk reduction between the PAXLOVID 5-day and 10-day PAXLOVID regimens versus placebo in the proportion of participants who developed symptomatic reverse transcriptase–polymerase chain reaction (RT-PCR) or rapid antigen test (RAT)-confirmed SARS-CoV-2 infection through Day 14 among participants who had a negative SARS-CoV-2 RT-PCR result at baseline, was not met.</p><p>Compared with placebo, the PAXLOVID 5-day and 10-day regimens led to a 30% and 36% relative risk reduction, respectively, in the risk of developing a symptomatic, RT-PCR or RAT confirmed SARS-CoV-2 infection through household contact; these results did not reach statistical significance.</p></div>"
}
}
]
},
{
"title": "5.2. Pharmacokinetic properties",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2",
"display": "5.2. Pharmacokinetic properties"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The pharmacokinetics of nirmatrelvir/ritonavir have been studied in healthy participants and in participants with mild-to-moderate COVID-19.</p><p>Ritonavir is administered with nirmatrelvir as a PK enhancer resulting in higher systemic concentrations and longer half-life of nirmatrelvir. In healthy participants in the fasted state, the mean half-life (t<sub>1/2</sub>) of a single dose of 150 mg nirmatrelvir administered alone was approximately 2 hours compared to 7 hours after administration of a single dose of 250 mg/100 mg nirmatrelvir/ritonavir thereby supporting a twice-daily administration regimen.</p><p>Upon administration of single dose of nirmatrelvir/ritonavir 250 mg/100 mg to healthy participants in the fasted state, the geometric mean (CV%) maximum plasma concentration (C<sub>max</sub>) and area under the plasma concentration-time curve from 0 to the time of last measurement (AUC<sub>last</sub>) was 2.88 ug/mL (25%) and 27.6 ug*h/mL (13%), respectively. Upon repeat-dose of nirmatrelvir/ritonavir 75 mg/100 mg, 250 mg/100 mg, and 500 mg/100 mg administered twice daily, the increase in systemic exposure at steady-state appears to be less than dose proportional. Multiple dosing over 10 days achieved steady-state on Day 2 with approximately 2-fold accumulation. Systemic exposures on Day 5 were similar to Day 10 across all doses. Simulated repeat-dose exposures of nirmatrelvir/ritonavir 300 mg/100 mg administered twice daily in adult participants from EPIC-HR, suggested the mean AUC<sub>tau</sub> was 28.3 µg*h/mL, mean C<sub>max</sub> was 3.29 µg/mL, and mean C<sub>min</sub> was 1.40 µg/mL.</p></div>"
},
"section": [
{
"title": "5.2.1. Absorption",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.1",
"display": "5.2.1. Absorption"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Following oral administration of nirmatrelvir/ritonavir 300 mg/100 mg after a single dose, the geometric mean nirmatrelvir (CV%) C<sub>max</sub> and area under the plasma concentration-time curve from 0 to infinity (AUC<sub>inf</sub>) at steady-state was 2.21 µg/mL (33) and 23.01 µg*h/mL (23), respectively. The median (range) time to C<sub>max</sub> (T<sub>max</sub>) was 3.00 h (1.02-6.00). The arithmetic mean (±SD) terminal elimination half-life was 6.1 (1.8) hours.</p><p>Following oral administration of nirmatrelvir/ritonavir 300 mg/100 mg after a single dose, the geometric mean ritonavir (CV%) C<sub>max</sub> and AUC<sub>inf</sub> was 0.36 µg/mL (46) and 3.60 µg*h/mL (47), respectively. The median (range) time to C<sub>max</sub> (T<sub>max</sub>) was 3.98 h (1.48-4.20). The arithmetic mean (±SD) terminal elimination half-life was 6.1 (2.2) hours.</p><p><i>Effect of food on oral absorption</i></p><p>Dosing with a high fat meal increased the exposure of nirmatrelvir (approximately 61% increase in mean C<sub>max</sub> and 20% increase in mean AUC<sub>last</sub>) relative to fasting conditions following administration of 300 mg nirmatrelvir (2 × 150 mg)/100 mg ritonavir tablets.</p></div>"
}
},
{
"title": "5.2.2. Distribution",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.2",
"display": "5.2.2. Distribution"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The protein binding of nirmatrelvir in human plasma is approximately 69%.</p><p>The protein binding of ritonavir in human plasma is approximately 98-99%.</p></div>"
}
},
{
"title": "5.2.3. Biotransformation",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.3",
"display": "5.2.3. Biotransformation"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>In vitro</i> studies assessing nirmatrelvir without concomitant ritonavir suggest that nirmatrelvir is primarily metabolized by CYP3A4. Nirmatrelvir is not a substrate of other CYP enzymes. Administration of nirmatrelvir with ritonavir inhibits the metabolism of nirmatrelvir. In human plasma, the only drug-related entity quantifiable was unchanged nirmatrelvir.</p><p><i>In vitro</i> studies utilizing human liver microsomes have demonstrated that cytochrome P450 3A (CYP3A) is the major isoform involved in ritonavir metabolism, although CYP2D6 also contributes to the formation of oxidation metabolite M–2.</p><p>Low doses of ritonavir have shown profound effects on the pharmacokinetics of other protease inhibitors (and other products metabolized by CYP3A4) and other protease inhibitors may influence the pharmacokinetics of ritonavir.</p></div>"
}
},
{
"title": "5.2.4. Elimination",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.4",
"display": "5.2.4. Elimination"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>The primary route of elimination of nirmatrelvir when administered with ritonavir was renal excretion of intact drug. Approximately 49.6% and 35.3% of the administered dose of nirmatrelvir 300 mg was recovered in urine and feces, respectively. Nirmatrelvir was the predominant drug-related entity with small amounts of metabolites arising from hydrolysis reactions in excreta.</p><p>Human studies with radiolabeled ritonavir demonstrated that the elimination of ritonavir was primarily via the hepatobiliary system; approximately 86% of radiolabel was recovered from stool, part of which is expected to be unabsorbed ritonavir.</p></div>"
}
},
{
"title": "5.2.5. Specific populations",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.5",
"display": "5.2.5. Specific populations"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Age and gender</i></p><p>In a population PK analysis, there were no clinically significant differences in the pharmacokinetics of nirmatrelvir based on age and gender.</p><p><i>Pediatric patients</i></p><p>The pharmacokinetics of nirmatrelvir/ritonavir in pediatric patients have not been evaluated.</p><p><i>Racial or ethnic groups</i></p><p>Systemic exposure in Japanese participants was numerically lower but not clinically meaningfully different than those in Western participants. In a population PK analysis, race did not affect the pharmacokinetics of nirmatrelvir.</p><p><i>Patients with renal impairment</i></p><p>Compared to healthy controls with no renal impairment, the C<sub>max</sub> and AUC<sub>inf</sub> of nirmatrelvir in participants with mild renal impairment were 30% and 24% higher, in patients with moderate renal impairment were 38% and 87% higher, and in participants with severe renal impairment were 48% and 204% higher, respectively.</p><p><i>Patients with severe renal impairment including those requiring hemodialysis</i></p><p>The pharmacokinetics of nirmatrelvir in participants with mild-to-moderate COVID-19 and severe renal impairment (eGFR <30 mL/min) either requiring hemodialysis (n=12) or not requiring hemodialysis (n=2) were evaluated after administration of 300 mg/100 mg nirmatrelvir/ritonavir once on Day 1 followed by 150 mg/100 mg nirmatrelvir/ritonavir once daily on Days 2-5 for a total of 5 doses.</p><p>During a 4-hour hemodialysis session, approximately 6.9% of nirmatrelvir dose was cleared through dialysis. Hemodialysis clearance was 1.83 L/h.</p><p>Population pharmacokinetic model-based simulations showed that administration of 300 mg/100 mg nirmatrelvir/ritonavir once on Day 1 followed by 150 mg/100 mg nirmatrelvir/ritonavir once daily on Days 2-5 in participants with severe renal impairment resulted in comparable exposures on Day 1 and at steady-state (AUC<sub>0-24</sub> and C<sub>max</sub>) to those observed in participants with normal renal function receiving 300 mg/100 mg nirmatrelvir/ritonavir twice daily for 5 days.</p><p><i>Patients with hepatic impairment</i></p><p>Compared to healthy controls with no hepatic impairment, the pharmacokinetics of nirmatrelvir in participants with moderate hepatic impairment were not significantly different. Adjusted geometric mean ratio (90% CI) of AUC<sub>inf</sub> and C<sub>max</sub> of nirmatrelvir comparing moderate hepatic impairment (test) to normal hepatic function (reference) were 98.78% (70.65%, 138.12%) and 101.96% (74.20%, 140.11%), respectively.</p><p>Nirmatrelvir/ritonavir has not been studied in patients with severe hepatic impairment.</p></div>"
}
},
{
"title": "5.2.6. Drug interaction studies conducted with nirmatrelvir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.6",
"display": "5.2.6. Drug interaction studies conducted with nirmatrelvir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>In vitro</i> data indicates that nirmatrelvir is a substrate for human MDR1 (P-gp) and CYP3A4, but not a substrate for human BCRP, MATE1, MATE2K, NTCP, OAT1, OAT2, OAT3, OCT1, OCT2, PEPT1, OATPs 1B1, 1B3, 2B1, or 4C1.</p><p>Nirmatrelvir does not reversibly inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 <i>in vitro</i> at clinically relevant concentrations. Nirmatrelvir has the potential to reversibly and time-dependently inhibit CYP3A4 and inhibit MDR1 (P-gp) and OATP1B1.</p><p>Nirmatrelvir does not induce any CYPs at clinically relevant concentrations.</p></div>"
}
},
{
"title": "5.2.7. Drug interaction studies conducted with nirmatrelvir/ritonavir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.2.7",
"display": "5.2.7. Drug interaction studies conducted with nirmatrelvir/ritonavir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>In vitro</i> studies indicate that ritonavir is mainly a substrate of CYP3A. Ritonavir also appears to be a substrate of CYP2D6 which contributes to the formation of isopropylthiazole oxidation metabolite M-2.</p><p>Ritonavir is an inhibitor of CYP3A and to a lesser extent CYP2D6. Ritonavir appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6 as well as other enzymes, including glucuronosyl transferase.</p><p>The effects of co-administration of PAXLOVID with itraconazole (CYP3A inhibitor) and carbamazepine (CYP3A inducer) on the nirmatrelvir AUC and C<sub>max</sub> are summarized in Table 9.</p><p><b>Table </b><b>9</b><b>:</b><b>\t</b><b>Effect of co-administered drugs on pharmacokinetics of nirmatrelvir</b></p><table><thead><tr><th><b>Co-administered drug</b></th><th colspan=\"2\"><b>Dose (schedule)</b></th><th><b>N</b></th><th colspan=\"2\"><b>Percent ratio of nirmatrelvir</b><b><sup>a</sup></b><b> PK parameters (90% CI);</b><br/><b>no effect=100</b></th></tr></thead><tbody><tr><td/><td><b>Co-administered</b></td><td><b>Nirmatrelvir/</b><b>\nritonavir</b></td><td/><td><b>C</b><b><sub>max</sub></b></td><td><b>AUC</b><b><sup>b</sup></b></td></tr><tr><td>Carbamazepine<sup>c</sup></td><td>300 mg<br/>twice daily<br/>(16 doses)</td><td>300 mg/100 mg once daily<br/>(2 doses)</td><td>10</td><td>56.82<br/>(47.04, 68.62)</td><td>44.50<br/>(33.77, 58.65)</td></tr><tr><td>Itraconazole</td><td>200 mg<br/>once daily<br/>(8 doses)</td><td>300 mg/100 mg twice daily<br/>(5 doses)</td><td>11</td><td>118.57<br/>(112.50, 124.97)</td><td>138.82<br/>(129.25, 149.11)</td></tr><tr><td colspan=\"6\">Abbreviations: AUC=area under the plasma concentration-time curve; CI=confidence interval; C<sub>max</sub>=observed maximum plasma concentrations; PK=pharmacokinetic.<br/>a.\tPercent ratio of test (i.e., carbamazepine or itraconazole in combination with nirmatrelvir/ritonavir)/reference (i.e., nirmatrelvir/ritonavir alone).<br/>b.\tFor carbamazepine, AUC=AUC<sub>inf</sub>; for itraconazole, AUC=AUC<sub>tau</sub>.<br/>c.\tCarbamazepine titrated up to 300 mg twice daily on Day 8 through Day 15 (e.g., 100 mg twice daily on Day 1 through Day 3 and 200 mg twice daily on Day 4 through Day 7).</td></tr></tbody></table><p>The effects of co-administration of PAXLOVID with midazolam (CYP3A4 substrate), dabigatran (P-gp substrate), or rosuvastatin (OATP1B1 substrate) on the midazolam, dabigatran, and rosuvastatin AUC<sub>inf</sub> and C<sub>max</sub>, respectively, are summarized in Table 10.</p><p><b>Table </b><b>10</b><b>:</b><b>\tEffect of nirmatrelvir/ritonavir on pharmacokinetics of co-administered drug</b></p><table><thead><tr><th><b>Co-administered drug</b></th><th colspan=\"2\"><b>Dose (schedule)</b></th><th><b>N</b></th><th colspan=\"2\"><b>Percent ratio</b><b><sup>a</sup></b><b> of test/reference of geometric means (90% CI);</b><br/><b>no effect=100</b></th></tr></thead><tbody><tr><td/><td><b>Co-administered</b></td><td><b>Nirmatrelvir/</b><b>\nritonavir</b></td><td/><td><b>C</b><b><sub>max</sub></b></td><td><b>AUC</b><b><sub>inf</sub></b></td></tr><tr><td>Midazolam<sup>b</sup></td><td>2 mg<br/>(1 dose)</td><td>300 mg/100 mg twice daily<br/>(9 doses)</td><td>10</td><td>368.33<br/>(318.91, 425.41)</td><td>1430.02<br/>(1204.54, 1697.71)</td></tr><tr><td>Dabigatran<sup>b</sup></td><td>75 mg<br/>(1 dose)</td><td>300 mg/100 mg twice daily<br/>(4 doses)</td><td>24</td><td>233.06<br/>(172.14, 315.54)</td><td>194.47<br/>(155.29, 243.55)</td></tr><tr><td>Rosuvastatin<sup>b</sup></td><td>10 mg<br/>(1 dose)</td><td>300 mg/100 mg twice daily<br/>(3 doses)</td><td>12</td><td>212.44<br/>(174.31, 258.90)</td><td>131.18<br/>(115.89, 148.48)</td></tr><tr><td colspan=\"6\">Abbreviations: AUC<sub>inf</sub>=area under the plasma concentration-time curve from time 0 to infinity; CI=confidence interval; C<sub>max</sub>=maximum plasma concentrations; CYP3A4=cytochrome P450 3A4; OATP1B1=organic anion transporting polypeptide 1B1; P-gp=P-glycoprotein.<br/>a.\tPercent ratio of test (i.e., midazolam, dabigatran, or rosuvastatin in combination with nirmatrelvir/ritonavir)/reference (i.e., midazolam, dabigatran, or rosuvastatin alone).<br/>b.\tFor midazolam, Test=nirmatrelvir/ritonavir plus midazolam, Reference=midazolam. Midazolam is an index substrate for CYP3A4. For dabigatran, Test=nirmatrelvir/ritonavir plus dabigatran, Reference=dabigatran. Dabigatran is an index substrate for P-gp. For rosuvastatin, Test=nirmatrelvir/ritonavir plus rosuvastatin, Reference=rosuvastatin. Rosuvastatin is an index substrate for OATP1B1.</td></tr></tbody></table></div>"
}
}
]
},
{
"title": "5.3. Preclinical safety data",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.3",
"display": "5.3. Preclinical safety data"
}
]
},
"section": [
{
"title": "5.3.1. Toxicology",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.3.1",
"display": "5.3.1. Toxicology"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Repeat-dose toxicity studies up to 1 month duration of nirmatrelvir in rats and monkeys resulted in no adverse findings.</p><p>Repeat-dose toxicity studies of ritonavir in animals identified major target organs as the liver, retina, thyroid gland, and kidney. Hepatic changes involved hepatocellular, biliary, and phagocytic elements and were accompanied by increases in hepatic enzymes. Hyperplasia of the retinal pigment epithelium and retinal degeneration have been seen in all of the rodent studies conducted with ritonavir, but have not been seen in dogs. Ultrastructural evidence suggests that these retinal changes may be secondary to phospholipidosis. However, clinical trials revealed no evidence of drug-induced ocular changes in humans. All thyroid changes were reversible upon discontinuation of ritonavir. Clinical investigation in humans has revealed no clinically significant alteration in thyroid function tests.</p><p>Renal changes including tubular degeneration, chronic inflammation and proteinuria were noted in rats and are considered to be attributable to species-specific spontaneous disease. Furthermore, no clinically significant renal abnormalities were noted in clinical trials.</p></div>"
}
},
{
"title": "5.3.2. Carcinogenesis",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.3.2",
"display": "5.3.2. Carcinogenesis"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Nirmatrelvir has not been evaluated for the potential to cause carcinogenicity.</p><p>Long-term carcinogenicity studies of ritonavir in mice and rats revealed tumorigenic potential specific for these species, but are regarded as of no relevance for humans.</p></div>"
}
},
{
"title": "5.3.3. Genotoxicity",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.3.3",
"display": "5.3.3. Genotoxicity"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Nirmatrelvir was not genotoxic in a battery of assays, including bacterial mutagenicity, chromosome aberration using human lymphoblastoid TK6 cells and <i>in vivo</i> rat micronucleus assays.</p><p>Ritonavir was found to be negative for mutagenic or clastogenic activity in a battery of <i>in vitro</i> and <i>in vivo</i> assays including the Ames bacterial reverse mutation assay using <i>S. typhimurium</i> and <i>E. coli</i>, the mouse lymphoma assay, the mouse micronucleus test, and chromosomal aberration assays in human lymphocytes.</p></div>"
}
},
{
"title": "5.3.4. Reproductive toxicity",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "5.3.4",
"display": "5.3.4. Reproductive toxicity"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Nirmatrelvir</i></p><p>In a fertility and early embryonic development study, there were no nirmatrelvir effects on fertility and reproductive performance at doses up to 1,000 mg/kg/day representing 5× clinical exposures at the approved dose of PAXLOVID.</p><p>Embryo-fetal developmental (EFD) toxicity studies were conducted in pregnant rats and rabbits administered oral nirmatrelvir doses of up to 1,000 mg/kg/day during organogenesis [on Gestation Days (GD) 6 through 17 in rats and GD 7 through 19 in rabbits]. No biologically significant developmental effects were observed in the rat EFD study. At the highest dose of 1,000 mg/kg/day, the systemic nirmatrelvir exposure (AUC<sub>24</sub>) in rats was approximately 9× higher than clinical exposures at the approved human dose of PAXLOVID. In the rabbit EFD study, lower fetal body weights (9% decrease) were observed at 1,000 mg/kg/day in the absence of significant maternal toxicity findings. At 1,000 mg/kg/day, the systemic exposure (AUC<sub>24</sub>) in rabbits was approximately 11× higher than clinical exposures at the approved human dose of PAXLOVID. No other significant developmental toxicities (malformations and embryo-fetal lethality) were observed at up to the highest dose tested, 1,000 mg/kg/day. No developmental effects were observed in rabbits at 300 mg/kg/day resulting in systemic exposure (AUC<sub>24</sub>) approximately 3× higher than clinical exposures at the approved human dose of PAXLOVID.</p><p>In the pre- and postnatal developmental study, body weight decreases (up to 8%) were observed in the offspring of pregnant rats administered nirmatrelvir at maternal systemic exposure (AUC<sub>24</sub>) approximately 9× higher than clinical exposures at the approved human dose of PAXLOVID. No body weight changes in the offspring were noted at maternal systemic exposure (AUC<sub>24</sub>) approximately 6× higher than clinical exposures at the approved human dose of PAXLOVID.</p><p><i>Ritonavir</i></p><p>Ritonavir produced no effects on fertility in rats.</p><p>Ritonavir was administered orally to pregnant rats (at 0, 15, 35, and 75 mg/kg/day) and rabbits (at 0, 25, 50, and 110 mg/kg/day) during organogenesis (on GD 6 through 17 in rats and GD 6 through 19 in rabbits). No evidence of teratogenicity due to ritonavir was observed in rats and rabbits at systemic exposures (AUC) 5× (rats) or 8× (rabbits) higher than exposure at the approved human dose of PAXLOVID. Increased incidences of early resorptions, ossification delays, and developmental variations, as well as decreased fetal body weights were observed in rats in the presence of maternal toxicity, at systemic exposures approximately 10× higher than exposure at the approved human dose of PAXLOVID.<sup> </sup>In rabbits, resorptions, decreased litter size, and decreased fetal weights were observed at maternally toxic doses, at systemic exposures greater than 8× higher than exposure at the approved human dose of PAXLOVID. In a pre- and postnatal development study in rats, administration of 0, 15, 35, and 60 mg/kg/day ritonavir from GD 6 through Postnatal Day 20 resulted in no developmental toxicity, at ritonavir systemic exposures greater than 10× the exposure at the approved human dose of PAXLOVID.</p></div>"
}
}
]
}
]
},
{
"title": "6. PHARMACEUTICAL PARTICULARS",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6",
"display": "6. PHARMACEUTICAL PARTICULARS"
}
]
},
"section": [
{
"title": "6.1. List of excipients",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.1",
"display": "6.1. List of excipients"
}
]
},
"section": [
{
"title": "6.1.1. Nirmatrelvir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.1.1",
"display": "6.1.1. Nirmatrelvir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Tablet core:</i></p><p><span data-res=\"ingr-exc-colloidal-silicon-dioxide\">Colloidal silicon dioxide</span></p><p><span data-res=\"ingr-exc-croscarmellose-sodium\">Croscarmellose sodium</span></p><p><span data-res=\"ingr-exc-lactose-monohydrate\">Lactose monohydrate</span></p><p><span data-res=\"ingr-exc-microcrystalline-cellulose\">Microcrystalline cellulose</span></p><p><span data-res=\"ingr-exc-sodium-stearyl-fumarate\">Sodium stearyl fumarate</span></p><p><i>Film coating:</i></p><p><span data-res=\"ingr-exc-hydroxy-propyl-methylcellulose\">Hydroxy propyl methylcellulose</span></p><p><span data-res=\"ingr-exc-iron-oxide-red\">Iron oxide red</span></p><p><span data-res=\"ingr-exc-polyethylene-glycol\">Polyethylene glycol</span></p><p><span data-res=\"ingr-exc-titanium-dioxide\">Titanium dioxide</span></p></div>"
},
"entry": [
{
"reference": "Ingredient/ingr-exc-colloidal-silicon-dioxide"
},
{
"reference": "Ingredient/ingr-exc-croscarmellose-sodium"
},
{
"reference": "Ingredient/ingr-exc-lactose-monohydrate"
},
{
"reference": "Ingredient/ingr-exc-microcrystalline-cellulose"
},
{
"reference": "Ingredient/ingr-exc-sodium-stearyl-fumarate"
},
{
"reference": "Ingredient/ingr-exc-hydroxy-propyl-methylcellulose"
},
{
"reference": "Ingredient/ingr-exc-iron-oxide-red"
},
{
"reference": "Ingredient/ingr-exc-polyethylene-glycol"
},
{
"reference": "Ingredient/ingr-exc-titanium-dioxide"
}
]
},
{
"title": "6.1.2. Hetero Ritonavir",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.1.2",
"display": "6.1.2. Hetero Ritonavir"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><i>Tablet core:</i></p><p><span data-res=\"ingr-exc-copovidone\">Copovidone</span></p><p><span data-res=\"ingr-exc-sorbitan-laurate\">Sorbitan laurate</span></p><p><span data-res=\"ingr-exc-silica-colloidal-anhydrous-e551\">Silica, colloidal anhydrous (E551)</span></p><p><span data-res=\"ingr-exc-calcium-hydrogen-phosphate\">Calcium hydrogen phosphate</span></p><p><span data-res=\"ingr-exc-sodium-stearyl-fumarate\">Sodium stearyl fumarate</span></p><p><i>Film coating:</i></p><p><span data-res=\"ingr-exc-hypromellose-e464\">Hypromellose (E464)</span></p><p><span data-res=\"ingr-exc-titanium-dioxide-e171\">Titanium dioxide (E171)</span></p><p><span data-res=\"ingr-exc-macrogol-e1521\">Macrogol (E1521)</span></p><p><span data-res=\"ingr-exc-hydroxypropyl-cellulose-e463\">Hydroxypropyl cellulose (E463)</span></p><p><span data-res=\"ingr-exc-talc-e553b\">Talc (E553b)</span></p><p><span data-res=\"ingr-exc-silica-colloidal-anhydrous-e551\">Silica, colloidal anhydrous (E551)</span></p><p><span data-res=\"ingr-exc-polysorbate-80-e433\">Polysorbate 80 (E433)</span></p></div>"
},
"entry": [
{
"reference": "Ingredient/ingr-exc-copovidone"
},
{
"reference": "Ingredient/ingr-exc-sorbitan-laurate"
},
{
"reference": "Ingredient/ingr-exc-silica-colloidal-anhydrous-e551"
},
{
"reference": "Ingredient/ingr-exc-calcium-hydrogen-phosphate"
},
{
"reference": "Ingredient/ingr-exc-sodium-stearyl-fumarate"
},
{
"reference": "Ingredient/ingr-exc-hypromellose-e464"
},
{
"reference": "Ingredient/ingr-exc-titanium-dioxide-e171"
},
{
"reference": "Ingredient/ingr-exc-macrogol-e1521"
},
{
"reference": "Ingredient/ingr-exc-hydroxypropyl-cellulose-e463"
},
{
"reference": "Ingredient/ingr-exc-talc-e553b"
},
{
"reference": "Ingredient/ingr-exc-silica-colloidal-anhydrous-e551"
},
{
"reference": "Ingredient/ingr-exc-polysorbate-80-e433"
}
]
}
]
},
{
"title": "6.2. Incompatibilities",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.2",
"display": "6.2. Incompatibilities"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Not applicable.</p></div>"
}
},
{
"title": "6.3. Shelf life",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.3",
"display": "6.3. Shelf life"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Refer to outer carton.</p></div>"
}
},
{
"title": "6.4. Special precautions for storage",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.4",
"display": "6.4. Special precautions for storage"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Store at or below 30°C.</p></div>"
}
},
{
"title": "6.5. Nature and contents of container",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.5",
"display": "6.5. Nature and contents of container"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Nirmatrelvir tablets and ritonavir tablets are supplied in separate <span id=\"ppd-paxlovid\">blister</span> cavities within the same blister card.</p><p>Each carton contains 30 tablets divided in 5 daily-dose blister cards.</p><p>Each daily blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and indicates which tablets need to be taken in the morning and evening.</p></div>"
},
"entry": [
{
"reference": "PackagedProductDefinition/ppd-paxlovid"
}
]
},
{
"title": "6.6. Special precautions for disposal and other handling",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "6.6",
"display": "6.6. Special precautions for disposal and other handling"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>No special requirements for disposal.</p><p>Any unused medicinal product or waste material should be disposed of in accordance with local requirements.</p></div>"
}
}
]
},
{
"title": "7. PRODUCT OWNER",
"code": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/section-code",
"code": "7",
"display": "7. PRODUCT OWNER"
}
]
},
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p><span id=\"org-owner\">Pfizer Inc.</span></p><p>New York,</p><p>United States</p><p>PAXH-SIN-0126/0</p><p>Date of last revision: January 2026</p></div>"
},
"entry": [
{
"reference": "Organization/org-owner"
}
]
}
]
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Organization/org-owner",
"resource": {
"resourceType": "Organization",
"id": "org-owner",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Organization_org-owner\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Organization org-owner</b></p><a name=\"org-owner\"> </a><a name=\"hcorg-owner\"> </a><p><b>identifier</b>: <code>https://www.hsa.gov.sg/epi/organisation</code>/PFIZER-INC</p><p><b>active</b>: true</p><p><b>name</b>: Pfizer Inc.</p><h3>Contacts</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Address</b></td></tr><tr><td style=\"display: none\">*</td><td>New York United States </td></tr></table></div>"
},
"identifier": [
{
"system": "https://www.hsa.gov.sg/epi/organisation",
"value": "PFIZER-INC"
}
],
"active": true,
"name": "Pfizer Inc.",
"contact": [
{
"address": {
"city": "New York",
"country": "United States"
}
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/MedicinalProductDefinition/mpd-paxlovid",
"resource": {
"resourceType": "MedicinalProductDefinition",
"id": "mpd-paxlovid",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"MedicinalProductDefinition_mpd-paxlovid\"> </a><p class=\"res-header-id\"><b>Generated Narrative: MedicinalProductDefinition mpd-paxlovid</b></p><a name=\"mpd-paxlovid\"> </a><a name=\"hcmpd-paxlovid\"> </a><p><b>identifier</b>: <code>https://www.hsa.gov.sg/epi/registration-number</code>/PAXH-SIN-0126</p><p><b>combinedPharmaceuticalDoseForm</b>: <span title=\"Codes:{https://standardterms.edqm.eu 10221000}\">Film-coated tablet</span></p><p><b>route</b>: <span title=\"Codes:{https://standardterms.edqm.eu 20053000}\">Oral use</span></p><blockquote><p><b>name</b></p><p><b>productName</b>: PAXLOVID</p><blockquote><p><b>part</b></p><p><b>part</b>: PAXLOVID</p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/medicinal-product-name-part-type InventedNamePart}\">Invented name part</span></p></blockquote><blockquote><p><b>part</b></p><p><b>part</b>: nirmatrelvir/ritonavir</p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/medicinal-product-name-part-type NonproprietaryNamePart}\">Nonproprietary name part</span></p></blockquote><blockquote><p><b>part</b></p><p><b>part</b>: 150 mg/100 mg</p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/medicinal-product-name-part-type StrengthPart}\">Strength part</span></p></blockquote><blockquote><p><b>part</b></p><p><b>part</b>: film-coated tablets</p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/medicinal-product-name-part-type DoseFormPart}\">Pharmaceutical dose form part</span></p></blockquote><h3>Usages</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Country</b></td><td><b>Jurisdiction</b></td><td><b>Language</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{urn:iso:std:iso:3166 SG}\">Singapore</span></td><td><span title=\"Codes:{urn:iso:std:iso:3166 SG}\">Singapore</span></td><td><span title=\"Codes:{urn:ietf:bcp:47 en}\">English</span></td></tr></table></blockquote></div>"
},
"identifier": [
{
"system": "https://www.hsa.gov.sg/epi/registration-number",
"value": "PAXH-SIN-0126"
}
],
"combinedPharmaceuticalDoseForm": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "10221000",
"display": "Film-coated tablet"
}
]
},
"route": [
{
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
}
],
"name": [
{
"productName": "PAXLOVID",
"part": [
{
"part": "PAXLOVID",
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/medicinal-product-name-part-type",
"code": "InventedNamePart",
"display": "Invented name part"
}
]
}
},
{
"part": "nirmatrelvir/ritonavir",
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/medicinal-product-name-part-type",
"code": "NonproprietaryNamePart",
"display": "Nonproprietary name part"
}
]
}
},
{
"part": "150 mg/100 mg",
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/medicinal-product-name-part-type",
"code": "StrengthPart",
"display": "Strength part"
}
]
}
},
{
"part": "film-coated tablets",
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/medicinal-product-name-part-type",
"code": "DoseFormPart",
"display": "Pharmaceutical dose form part"
}
]
}
}
],
"usage": [
{
"country": {
"coding": [
{
"system": "urn:iso:std:iso:3166",
"code": "SG",
"display": "Singapore"
}
]
},
"jurisdiction": {
"coding": [
{
"system": "urn:iso:std:iso:3166",
"code": "SG",
"display": "Singapore"
}
]
},
"language": {
"coding": [
{
"system": "urn:ietf:bcp:47",
"code": "en",
"display": "English"
}
]
}
}
]
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/RegulatedAuthorization/regauth-paxlovid",
"resource": {
"resourceType": "RegulatedAuthorization",
"id": "regauth-paxlovid",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"RegulatedAuthorization_regauth-paxlovid\"> </a><p class=\"res-header-id\"><b>Generated Narrative: RegulatedAuthorization regauth-paxlovid</b></p><a name=\"regauth-paxlovid\"> </a><a name=\"hcregauth-paxlovid\"> </a><p><b>identifier</b>: <code>https://www.hsa.gov.sg/epi/registration-number</code>/PAXH-SIN-0126 (draft — HSA to confirm)</p><p><b>subject</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>status</b>: <span title=\"Codes:{http://hl7.org/fhir/publication-status active}\">Active</span></p><p><b>holder</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#Organization_org-owner\">Organization Pfizer Inc.</a></p></div>"
},
"identifier": [
{
"system": "https://www.hsa.gov.sg/epi/registration-number",
"value": "PAXH-SIN-0126 (draft — HSA to confirm)"
}
],
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"status": {
"coding": [
{
"system": "http://hl7.org/fhir/publication-status",
"code": "active"
}
]
},
"holder": {
"reference": "Organization/org-owner"
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/SubstanceDefinition/subd-nirmatrelvir",
"resource": {
"resourceType": "SubstanceDefinition",
"id": "subd-nirmatrelvir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"SubstanceDefinition_subd-nirmatrelvir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: SubstanceDefinition subd-nirmatrelvir</b></p><a name=\"subd-nirmatrelvir\"> </a><a name=\"hcsubd-nirmatrelvir\"> </a><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Code</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{http://fdasis.nlm.nih.gov 7R9A5P7H32}\">Nirmatrelvir</span></td></tr></table><h3>Names</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Name</b></td></tr><tr><td style=\"display: none\">*</td><td>Nirmatrelvir</td></tr></table></div>"
},
"code": [
{
"code": {
"coding": [
{
"system": "http://fdasis.nlm.nih.gov",
"code": "7R9A5P7H32",
"display": "Nirmatrelvir"
}
]
}
}
],
"name": [
{
"name": "Nirmatrelvir"
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/SubstanceDefinition/subd-ritonavir",
"resource": {
"resourceType": "SubstanceDefinition",
"id": "subd-ritonavir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"SubstanceDefinition_subd-ritonavir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: SubstanceDefinition subd-ritonavir</b></p><a name=\"subd-ritonavir\"> </a><a name=\"hcsubd-ritonavir\"> </a><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Code</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{http://fdasis.nlm.nih.gov O3J8G9O825}\">Ritonavir</span></td></tr></table><h3>Names</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Name</b></td></tr><tr><td style=\"display: none\">*</td><td>Ritonavir</td></tr></table></div>"
},
"code": [
{
"code": {
"coding": [
{
"system": "http://fdasis.nlm.nih.gov",
"code": "O3J8G9O825",
"display": "Ritonavir"
}
]
}
}
],
"name": [
{
"name": "Ritonavir"
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/SubstanceDefinition/subd-lactose",
"resource": {
"resourceType": "SubstanceDefinition",
"id": "subd-lactose",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"SubstanceDefinition_subd-lactose\"> </a><p class=\"res-header-id\"><b>Generated Narrative: SubstanceDefinition subd-lactose</b></p><a name=\"subd-lactose\"> </a><a name=\"hcsubd-lactose\"> </a><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Code</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{http://fdasis.nlm.nih.gov EWQ57Q8I5X}\">Lactose monohydrate</span></td></tr></table><h3>Names</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Name</b></td></tr><tr><td style=\"display: none\">*</td><td>Lactose monohydrate</td></tr></table></div>"
},
"code": [
{
"code": {
"coding": [
{
"system": "http://fdasis.nlm.nih.gov",
"code": "EWQ57Q8I5X",
"display": "Lactose monohydrate"
}
]
}
}
],
"name": [
{
"name": "Lactose monohydrate"
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-nirmatrelvir",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-nirmatrelvir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-nirmatrelvir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-nirmatrelvir</b></p><a name=\"ingr-nirmatrelvir\"> </a><a name=\"hcingr-nirmatrelvir\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role active}\">active</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/substance subd-nirmatrelvir}\">Nirmatrelvir</span></td></tr></table><h3>Strengths</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Presentation[x]</b></td></tr><tr><td style=\"display: none\">*</td><td>150 mg<span style=\"background: LightGoldenRodYellow\"> (Details: UCUM codemg = 'mg')</span>/1 film-coated tablet<span style=\"background: LightGoldenRodYellow\"> (Details: standardterms.edqm.eu code10221000 = '10221000')</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "active"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/substance",
"code": "subd-nirmatrelvir",
"display": "Nirmatrelvir"
}
]
}
},
"strength": [
{
"presentationRatio": {
"numerator": {
"value": 150,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
},
"denominator": {
"value": 1,
"unit": "film-coated tablet",
"system": "https://standardterms.edqm.eu",
"code": "10221000"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-ritonavir",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-ritonavir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-ritonavir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-ritonavir</b></p><a name=\"ingr-ritonavir\"> </a><a name=\"hcingr-ritonavir\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role active}\">active</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/substance subd-ritonavir}\">Ritonavir</span></td></tr></table><h3>Strengths</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Presentation[x]</b></td></tr><tr><td style=\"display: none\">*</td><td>100 mg<span style=\"background: LightGoldenRodYellow\"> (Details: UCUM codemg = 'mg')</span>/1 film-coated tablet<span style=\"background: LightGoldenRodYellow\"> (Details: standardterms.edqm.eu code10221000 = '10221000')</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "active"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/substance",
"code": "subd-ritonavir",
"display": "Ritonavir"
}
]
}
},
"strength": [
{
"presentationRatio": {
"numerator": {
"value": 100,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
},
"denominator": {
"value": 1,
"unit": "film-coated tablet",
"system": "https://standardterms.edqm.eu",
"code": "10221000"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-lactose",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-lactose",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-lactose\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-lactose</b></p><a name=\"ingr-lactose\"> </a><a name=\"hcingr-lactose\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/substance subd-lactose}\">Lactose monohydrate</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/substance",
"code": "subd-lactose",
"display": "Lactose monohydrate"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-colloidal-silicon-dioxide",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-colloidal-silicon-dioxide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-colloidal-silicon-dioxide\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-colloidal-silicon-dioxide</b></p><a name=\"ingr-exc-colloidal-silicon-dioxide\"> </a><a name=\"hcingr-exc-colloidal-silicon-dioxide\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance colloidal-silicon-dioxide}\">Colloidal silicon dioxide</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "colloidal-silicon-dioxide",
"display": "Colloidal silicon dioxide"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-croscarmellose-sodium",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-croscarmellose-sodium",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-croscarmellose-sodium\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-croscarmellose-sodium</b></p><a name=\"ingr-exc-croscarmellose-sodium\"> </a><a name=\"hcingr-exc-croscarmellose-sodium\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance croscarmellose-sodium}\">Croscarmellose sodium</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "croscarmellose-sodium",
"display": "Croscarmellose sodium"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-lactose-monohydrate",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-lactose-monohydrate",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-lactose-monohydrate\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-lactose-monohydrate</b></p><a name=\"ingr-exc-lactose-monohydrate\"> </a><a name=\"hcingr-exc-lactose-monohydrate\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance lactose-monohydrate}\">Lactose monohydrate</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lactose-monohydrate",
"display": "Lactose monohydrate"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-microcrystalline-cellulose",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-microcrystalline-cellulose",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-microcrystalline-cellulose\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-microcrystalline-cellulose</b></p><a name=\"ingr-exc-microcrystalline-cellulose\"> </a><a name=\"hcingr-exc-microcrystalline-cellulose\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance microcrystalline-cellulose}\">Microcrystalline cellulose</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "microcrystalline-cellulose",
"display": "Microcrystalline cellulose"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-sodium-stearyl-fumarate",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-sodium-stearyl-fumarate",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-sodium-stearyl-fumarate\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-sodium-stearyl-fumarate</b></p><a name=\"ingr-exc-sodium-stearyl-fumarate\"> </a><a name=\"hcingr-exc-sodium-stearyl-fumarate\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance sodium-stearyl-fumarate}\">Sodium stearyl fumarate</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "sodium-stearyl-fumarate",
"display": "Sodium stearyl fumarate"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-hydroxy-propyl-methylcellulose",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-hydroxy-propyl-methylcellulose",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-hydroxy-propyl-methylcellulose\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-hydroxy-propyl-methylcellulose</b></p><a name=\"ingr-exc-hydroxy-propyl-methylcellulose\"> </a><a name=\"hcingr-exc-hydroxy-propyl-methylcellulose\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance hydroxy-propyl-methylcellulose}\">Hydroxy propyl methylcellulose</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "hydroxy-propyl-methylcellulose",
"display": "Hydroxy propyl methylcellulose"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-iron-oxide-red",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-iron-oxide-red",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-iron-oxide-red\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-iron-oxide-red</b></p><a name=\"ingr-exc-iron-oxide-red\"> </a><a name=\"hcingr-exc-iron-oxide-red\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance iron-oxide-red}\">Iron oxide red</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "iron-oxide-red",
"display": "Iron oxide red"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-polyethylene-glycol",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-polyethylene-glycol",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-polyethylene-glycol\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-polyethylene-glycol</b></p><a name=\"ingr-exc-polyethylene-glycol\"> </a><a name=\"hcingr-exc-polyethylene-glycol\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance polyethylene-glycol}\">Polyethylene glycol</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "polyethylene-glycol",
"display": "Polyethylene glycol"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-titanium-dioxide",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-titanium-dioxide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-titanium-dioxide\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-titanium-dioxide</b></p><a name=\"ingr-exc-titanium-dioxide\"> </a><a name=\"hcingr-exc-titanium-dioxide\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance titanium-dioxide}\">Titanium dioxide</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "titanium-dioxide",
"display": "Titanium dioxide"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-copovidone",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-copovidone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-copovidone\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-copovidone</b></p><a name=\"ingr-exc-copovidone\"> </a><a name=\"hcingr-exc-copovidone\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance copovidone}\">Copovidone</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "copovidone",
"display": "Copovidone"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-sorbitan-laurate",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-sorbitan-laurate",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-sorbitan-laurate\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-sorbitan-laurate</b></p><a name=\"ingr-exc-sorbitan-laurate\"> </a><a name=\"hcingr-exc-sorbitan-laurate\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance sorbitan-laurate}\">Sorbitan laurate</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "sorbitan-laurate",
"display": "Sorbitan laurate"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-silica-colloidal-anhydrous-e551",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-silica-colloidal-anhydrous-e551",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-silica-colloidal-anhydrous-e551\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-silica-colloidal-anhydrous-e551</b></p><a name=\"ingr-exc-silica-colloidal-anhydrous-e551\"> </a><a name=\"hcingr-exc-silica-colloidal-anhydrous-e551\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance silica-colloidal-anhydrous-e551}\">Silica, colloidal anhydrous (E551)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "silica-colloidal-anhydrous-e551",
"display": "Silica, colloidal anhydrous (E551)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-calcium-hydrogen-phosphate",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-calcium-hydrogen-phosphate",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-calcium-hydrogen-phosphate\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-calcium-hydrogen-phosphate</b></p><a name=\"ingr-exc-calcium-hydrogen-phosphate\"> </a><a name=\"hcingr-exc-calcium-hydrogen-phosphate\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance calcium-hydrogen-phosphate}\">Calcium hydrogen phosphate</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "calcium-hydrogen-phosphate",
"display": "Calcium hydrogen phosphate"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-hypromellose-e464",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-hypromellose-e464",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-hypromellose-e464\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-hypromellose-e464</b></p><a name=\"ingr-exc-hypromellose-e464\"> </a><a name=\"hcingr-exc-hypromellose-e464\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance hypromellose-e464}\">Hypromellose (E464)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "hypromellose-e464",
"display": "Hypromellose (E464)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-titanium-dioxide-e171",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-titanium-dioxide-e171",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-titanium-dioxide-e171\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-titanium-dioxide-e171</b></p><a name=\"ingr-exc-titanium-dioxide-e171\"> </a><a name=\"hcingr-exc-titanium-dioxide-e171\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance titanium-dioxide-e171}\">Titanium dioxide (E171)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "titanium-dioxide-e171",
"display": "Titanium dioxide (E171)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-macrogol-e1521",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-macrogol-e1521",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-macrogol-e1521\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-macrogol-e1521</b></p><a name=\"ingr-exc-macrogol-e1521\"> </a><a name=\"hcingr-exc-macrogol-e1521\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance macrogol-e1521}\">Macrogol (E1521)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "macrogol-e1521",
"display": "Macrogol (E1521)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-hydroxypropyl-cellulose-e463",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-hydroxypropyl-cellulose-e463",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-hydroxypropyl-cellulose-e463\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-hydroxypropyl-cellulose-e463</b></p><a name=\"ingr-exc-hydroxypropyl-cellulose-e463\"> </a><a name=\"hcingr-exc-hydroxypropyl-cellulose-e463\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance hydroxypropyl-cellulose-e463}\">Hydroxypropyl cellulose (E463)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "hydroxypropyl-cellulose-e463",
"display": "Hydroxypropyl cellulose (E463)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-talc-e553b",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-talc-e553b",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-talc-e553b\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-talc-e553b</b></p><a name=\"ingr-exc-talc-e553b\"> </a><a name=\"hcingr-exc-talc-e553b\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance talc-e553b}\">Talc (E553b)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "talc-e553b",
"display": "Talc (E553b)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/Ingredient/ingr-exc-polysorbate-80-e433",
"resource": {
"resourceType": "Ingredient",
"id": "ingr-exc-polysorbate-80-e433",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"Ingredient_ingr-exc-polysorbate-80-e433\"> </a><p class=\"res-header-id\"><b>Generated Narrative: Ingredient ingr-exc-polysorbate-80-e433</b></p><a name=\"ingr-exc-polysorbate-80-e433\"> </a><a name=\"hcingr-exc-polysorbate-80-e433\"> </a><p><b>status</b>: Active</p><p><b>for</b>: <a href=\"Bundle-paxlovid-sgp-pil-epi.html#MedicinalProductDefinition_mpd-paxlovid\">MedicinalProductDefinition: identifier = https://www.hsa.gov.sg/epi/registration-number#PAXH-SIN-0126; combinedPharmaceuticalDoseForm = Film-coated tablet; route = Oral use</a></p><p><b>role</b>: <span title=\"Codes:{http://hl7.org/fhir/ingredient-role excipient}\">excipient</span></p><blockquote><p><b>substance</b></p><h3>Codes</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Concept</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://www.hsa.gov.sg/epi/draft-substance polysorbate-80-e433}\">Polysorbate 80 (E433)</span></td></tr></table></blockquote></div>"
},
"status": "active",
"for": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"role": {
"coding": [
{
"system": "http://hl7.org/fhir/ingredient-role",
"code": "excipient"
}
]
},
"substance": {
"code": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "polysorbate-80-e433",
"display": "Polysorbate 80 (E433)"
}
]
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ManufacturedItemDefinition/mid-nirmatrelvir",
"resource": {
"resourceType": "ManufacturedItemDefinition",
"id": "mid-nirmatrelvir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ManufacturedItemDefinition_mid-nirmatrelvir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: ManufacturedItemDefinition mid-nirmatrelvir</b></p><a name=\"mid-nirmatrelvir\"> </a><a name=\"hcmid-nirmatrelvir\"> </a><p><b>status</b>: Active</p><p><b>name</b>: Nirmatrelvir 150 mg film-coated tablet</p><p><b>manufacturedDoseForm</b>: <span title=\"Codes:{https://standardterms.edqm.eu 10221000}\">Film-coated tablet</span></p><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig color}\">Color</span></p><p><b>value</b>: <span title=\"Codes:\">Pink</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig shape}\">Shape</span></p><p><b>value</b>: <span title=\"Codes:\">Oval</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig size}\">Size</span></p><p><b>value</b>: </p><div><p>Approximately 17.6 mm in length and 8.6 mm in width</p>\n</div></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig imprint}\">Imprint</span></p><p><b>value</b>: </p><div><p>Debossed with ‘PFE’ on one side and ‘3CL’ on the other side</p>\n</div></blockquote></div>"
},
"status": "active",
"name": "Nirmatrelvir 150 mg film-coated tablet",
"manufacturedDoseForm": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "10221000",
"display": "Film-coated tablet"
}
]
},
"property": [
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "color",
"display": "Color"
}
]
},
"valueCodeableConcept": {
"text": "Pink"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "shape",
"display": "Shape"
}
]
},
"valueCodeableConcept": {
"text": "Oval"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "size",
"display": "Size"
}
]
},
"valueMarkdown": "Approximately 17.6 mm in length and 8.6 mm in width"
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "imprint",
"display": "Imprint"
}
]
},
"valueMarkdown": "Debossed with ‘PFE’ on one side and ‘3CL’ on the other side"
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ManufacturedItemDefinition/mid-ritonavir",
"resource": {
"resourceType": "ManufacturedItemDefinition",
"id": "mid-ritonavir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ManufacturedItemDefinition_mid-ritonavir\"> </a><p class=\"res-header-id\"><b>Generated Narrative: ManufacturedItemDefinition mid-ritonavir</b></p><a name=\"mid-ritonavir\"> </a><a name=\"hcmid-ritonavir\"> </a><p><b>status</b>: Active</p><p><b>name</b>: Ritonavir 100 mg film-coated tablet</p><p><b>manufacturedDoseForm</b>: <span title=\"Codes:{https://standardterms.edqm.eu 10221000}\">Film-coated tablet</span></p><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig color}\">Color</span></p><p><b>value</b>: <span title=\"Codes:\">White to off white</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig shape}\">Shape</span></p><p><b>value</b>: <span title=\"Codes:\">Capsule shaped</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig imprint}\">Imprint</span></p><p><b>value</b>: </p><div><p>Debossed with ‘H’ on one side and ‘R9’ on the other side</p>\n</div></blockquote></div>"
},
"status": "active",
"name": "Ritonavir 100 mg film-coated tablet",
"manufacturedDoseForm": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "10221000",
"display": "Film-coated tablet"
}
]
},
"property": [
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "color",
"display": "Color"
}
]
},
"valueCodeableConcept": {
"text": "White to off white"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "shape",
"display": "Shape"
}
]
},
"valueCodeableConcept": {
"text": "Capsule shaped"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "imprint",
"display": "Imprint"
}
]
},
"valueMarkdown": "Debossed with ‘H’ on one side and ‘R9’ on the other side"
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/AdministrableProductDefinition/apd-paxlovid",
"resource": {
"resourceType": "AdministrableProductDefinition",
"id": "apd-paxlovid",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"AdministrableProductDefinition_apd-paxlovid\"> </a><p class=\"res-header-id\"><b>Generated Narrative: AdministrableProductDefinition apd-paxlovid</b></p><a name=\"apd-paxlovid\"> </a><a name=\"hcapd-paxlovid\"> </a><p><b>status</b>: Active</p><p><b>administrableDoseForm</b>: <span title=\"Codes:{https://standardterms.edqm.eu 10221000}\">Film-coated tablet</span></p><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig color}\">Color</span></p><p><b>value</b>: <span title=\"Codes:\">Pink (nirmatrelvir tablet); white to off white (ritonavir tablet)</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig shape}\">Shape</span></p><p><b>value</b>: <span title=\"Codes:\">Oval (nirmatrelvir tablet); capsule shaped (ritonavir tablet)</span></p></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig size}\">Size</span></p><p><b>value</b>: </p><div><p>Nirmatrelvir tablet approximately 17.6 mm in length and 8.6 mm in width</p>\n</div></blockquote><blockquote><p><b>property</b></p><p><b>type</b>: <span title=\"Codes:{http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig imprint}\">Imprint</span></p><p><b>value</b>: </p><div><p>Nirmatrelvir tablet debossed ‘PFE’/‘3CL’; ritonavir tablet debossed ‘H’/‘R9’</p>\n</div></blockquote><h3>RouteOfAdministrations</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Code</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://standardterms.edqm.eu 20053000}\">Oral use</span></td></tr></table></div>"
},
"status": "active",
"administrableDoseForm": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "10221000",
"display": "Film-coated tablet"
}
]
},
"property": [
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "color",
"display": "Color"
}
]
},
"valueCodeableConcept": {
"text": "Pink (nirmatrelvir tablet); white to off white (ritonavir tablet)"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "shape",
"display": "Shape"
}
]
},
"valueCodeableConcept": {
"text": "Oval (nirmatrelvir tablet); capsule shaped (ritonavir tablet)"
}
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "size",
"display": "Size"
}
]
},
"valueMarkdown": "Nirmatrelvir tablet approximately 17.6 mm in length and 8.6 mm in width"
},
{
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/uv/emedicinal-product-info/CodeSystem/epi-ig",
"code": "imprint",
"display": "Imprint"
}
]
},
"valueMarkdown": "Nirmatrelvir tablet debossed ‘PFE’/‘3CL’; ritonavir tablet debossed ‘H’/‘R9’"
}
],
"routeOfAdministration": [
{
"code": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
}
}
]
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/PackagedProductDefinition/ppd-paxlovid",
"resource": {
"resourceType": "PackagedProductDefinition",
"id": "ppd-paxlovid",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"PackagedProductDefinition_ppd-paxlovid\"> </a><p class=\"res-header-id\"><b>Generated Narrative: PackagedProductDefinition ppd-paxlovid</b></p><a name=\"ppd-paxlovid\"> </a><a name=\"hcppd-paxlovid\"> </a><p><b>name</b>: PAXLOVID film-coated tablets — daily-dose co-pack (nirmatrelvir + ritonavir)</p><h3>Packagings</h3><table class=\"grid\"><tr><td style=\"display: none\">-</td><td><b>Type</b></td><td><b>Quantity</b></td></tr><tr><td style=\"display: none\">*</td><td><span title=\"Codes:{https://standardterms.edqm.eu 30007000}\">Carton</span></td><td>30</td></tr></table></div>"
},
"name": "PAXLOVID film-coated tablets — daily-dose co-pack (nirmatrelvir + ritonavir)",
"packaging": {
"quantity": 30,
"type": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "30007000",
"display": "Carton"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ind-1",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ind-1",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ind-1\"> </a><p>Treatment of mild-to-moderate COVID-19 in adults at high risk of progression to severe disease.</p></div>"
},
"type": "indication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"indication": {
"diseaseSymptomProcedure": {
"concept": {
"coding": [
{
"system": "http://snomed.info/sct",
"code": "840539006",
"display": "Disease caused by SARS-CoV-2"
}
],
"text": "Mild-to-moderate COVID-19 in adults at high risk for progression to severe COVID-19"
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-hypersensitivity",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-hypersensitivity",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-hypersensitivity\"> </a><p>Contraindicated in clinically significant hypersensitivity to nirmatrelvir or ritonavir or any excipient.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"diseaseSymptomProcedure": {
"concept": {
"coding": [
{
"system": "http://snomed.info/sct",
"code": "473011001",
"display": "Allergic condition"
}
],
"text": "Hypersensitivity to the active substances (nirmatrelvir/ritonavir) or excipients"
}
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-01-alfuzosin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-01-alfuzosin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-01-alfuzosin\"> </a><p>Co-administration with alfuzosin (Alpha 1-adrenoreceptor antagonist) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "alfuzosin",
"display": "alfuzosin"
}
],
"text": "Alpha 1-adrenoreceptor antagonist: alfuzosin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-02-ranolazine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-02-ranolazine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-02-ranolazine\"> </a><p>Co-administration with ranolazine (Antianginal) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ranolazine",
"display": "ranolazine"
}
],
"text": "Antianginal: ranolazine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-03-amiodarone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-03-amiodarone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-03-amiodarone\"> </a><p>Co-administration with amiodarone (Antiarrhythmic) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "amiodarone",
"display": "amiodarone"
}
],
"text": "Antiarrhythmic: amiodarone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-04-dronedarone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-04-dronedarone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-04-dronedarone\"> </a><p>Co-administration with dronedarone (Antiarrhythmic) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "dronedarone",
"display": "dronedarone"
}
],
"text": "Antiarrhythmic: dronedarone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-05-flecainide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-05-flecainide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-05-flecainide\"> </a><p>Co-administration with flecainide (Antiarrhythmic) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "flecainide",
"display": "flecainide"
}
],
"text": "Antiarrhythmic: flecainide"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-06-propafenone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-06-propafenone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-06-propafenone\"> </a><p>Co-administration with propafenone (Antiarrhythmic) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "propafenone",
"display": "propafenone"
}
],
"text": "Antiarrhythmic: propafenone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-07-quinidine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-07-quinidine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-07-quinidine\"> </a><p>Co-administration with quinidine (Antiarrhythmic) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "quinidine",
"display": "quinidine"
}
],
"text": "Antiarrhythmic: quinidine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-08-colchicine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-08-colchicine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-08-colchicine\"> </a><p>Co-administration with colchicine (Anti-gout) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "colchicine",
"display": "colchicine"
}
],
"text": "Anti-gout: colchicine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-09-lurasidone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-09-lurasidone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-09-lurasidone\"> </a><p>Co-administration with lurasidone (Antipsychotics) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lurasidone",
"display": "lurasidone"
}
],
"text": "Antipsychotics: lurasidone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-10-pimozide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-10-pimozide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-10-pimozide\"> </a><p>Co-administration with pimozide (Antipsychotics) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "pimozide",
"display": "pimozide"
}
],
"text": "Antipsychotics: pimozide"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-11-silodosin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-11-silodosin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-11-silodosin\"> </a><p>Co-administration with silodosin (Benign prostatic hyperplasia agents) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "silodosin",
"display": "silodosin"
}
],
"text": "Benign prostatic hyperplasia agents: silodosin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-12-eplerenone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-12-eplerenone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-12-eplerenone\"> </a><p>Co-administration with eplerenone (Cardiovascular agents) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "eplerenone",
"display": "eplerenone"
}
],
"text": "Cardiovascular agents: eplerenone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-13-ivabradine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-13-ivabradine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-13-ivabradine\"> </a><p>Co-administration with ivabradine (Cardiovascular agents) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ivabradine",
"display": "ivabradine"
}
],
"text": "Cardiovascular agents: ivabradine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-14-dihydroergotamine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-14-dihydroergotamine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-14-dihydroergotamine\"> </a><p>Co-administration with dihydroergotamine (Ergot derivatives) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "dihydroergotamine",
"display": "dihydroergotamine"
}
],
"text": "Ergot derivatives: dihydroergotamine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-15-ergotamine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-15-ergotamine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-15-ergotamine\"> </a><p>Co-administration with ergotamine (Ergot derivatives) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ergotamine",
"display": "ergotamine"
}
],
"text": "Ergot derivatives: ergotamine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-16-methylergonovine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-16-methylergonovine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-16-methylergonovine\"> </a><p>Co-administration with methylergonovine (Ergot derivatives) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "methylergonovine",
"display": "methylergonovine"
}
],
"text": "Ergot derivatives: methylergonovine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-17-lovastatin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-17-lovastatin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-17-lovastatin\"> </a><p>Co-administration with lovastatin (HMG-CoA reductase inhibitors) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lovastatin",
"display": "lovastatin"
}
],
"text": "HMG-CoA reductase inhibitors: lovastatin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-18-simvastatin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-18-simvastatin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-18-simvastatin\"> </a><p>Co-administration with simvastatin (HMG-CoA reductase inhibitors) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "simvastatin",
"display": "simvastatin"
}
],
"text": "HMG-CoA reductase inhibitors: simvastatin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-19-voclosporin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-19-voclosporin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-19-voclosporin\"> </a><p>Co-administration with voclosporin (Immunosuppressants) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "voclosporin",
"display": "voclosporin"
}
],
"text": "Immunosuppressants: voclosporin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-20-lomitapide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-20-lomitapide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-20-lomitapide\"> </a><p>Co-administration with lomitapide (Microsomal triglyceride transfer protein inhibitor) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lomitapide",
"display": "lomitapide"
}
],
"text": "Microsomal triglyceride transfer protein inhibitor: lomitapide"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-21-eletriptan",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-21-eletriptan",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-21-eletriptan\"> </a><p>Co-administration with eletriptan (Migraine medications) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "eletriptan",
"display": "eletriptan"
}
],
"text": "Migraine medications: eletriptan"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-22-ubrogepant",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-22-ubrogepant",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-22-ubrogepant\"> </a><p>Co-administration with ubrogepant (Migraine medications) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ubrogepant",
"display": "ubrogepant"
}
],
"text": "Migraine medications: ubrogepant"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-23-finerenone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-23-finerenone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-23-finerenone\"> </a><p>Co-administration with finerenone (Mineralocorticoid receptor antagonists) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "finerenone",
"display": "finerenone"
}
],
"text": "Mineralocorticoid receptor antagonists: finerenone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-24-suzetrigine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-24-suzetrigine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-24-suzetrigine\"> </a><p>Co-administration with suzetrigine (Non-opioid analgesic (selective blocker of Nav1.8 sodium channels)) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "suzetrigine",
"display": "suzetrigine"
}
],
"text": "Non-opioid analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-25-naloxegol",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-25-naloxegol",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-25-naloxegol\"> </a><p>Co-administration with naloxegol (Opioid antagonists) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "naloxegol",
"display": "naloxegol"
}
],
"text": "Opioid antagonists: naloxegol"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-26-sildenafil-when-used-for-pulmonary-arterial-hype",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-26-sildenafil-when-used-for-pulmonary-arterial-hype",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-26-sildenafil-when-used-for-pulmonary-arterial-hype\"> </a><p>Co-administration with sildenafil when used for pulmonary arterial hypertension (PAH) (PDE5 inhibitor) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "sildenafil-when-used-for-pulmonary-arterial-hype",
"display": "sildenafil when used for pulmonary arterial hypertension (PAH)"
}
],
"text": "PDE5 inhibitor: sildenafil when used for pulmonary arterial hypertension (PAH)"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-27-triazolam",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-27-triazolam",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-27-triazolam\"> </a><p>Co-administration with triazolam (Sedative/hypnotics) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "triazolam",
"display": "triazolam"
}
],
"text": "Sedative/hypnotics: triazolam"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-28-oral-midazolam",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-28-oral-midazolam",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-28-oral-midazolam\"> </a><p>Co-administration with oral midazolam (Sedative/hypnotics) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "oral-midazolam",
"display": "oral midazolam"
}
],
"text": "Sedative/hypnotics: oral midazolam"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-29-flibanserin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-29-flibanserin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-29-flibanserin\"> </a><p>Co-administration with flibanserin (Serotonin receptor 1A agonist/serotonin receptor 2A antagonist) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "flibanserin",
"display": "flibanserin"
}
],
"text": "Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-30-tolvaptan",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-30-tolvaptan",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-30-tolvaptan\"> </a><p>Co-administration with tolvaptan (Vasopressin receptor antagonists) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "tolvaptan",
"display": "tolvaptan"
}
],
"text": "Vasopressin receptor antagonists: tolvaptan"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-31-apalutamide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-31-apalutamide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-31-apalutamide\"> </a><p>Co-administration with apalutamide (Anticancer drugs) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "apalutamide",
"display": "apalutamide"
}
],
"text": "Anticancer drugs: apalutamide"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-32-enzalutamide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-32-enzalutamide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-32-enzalutamide\"> </a><p>Co-administration with enzalutamide (Anticancer drugs) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "enzalutamide",
"display": "enzalutamide"
}
],
"text": "Anticancer drugs: enzalutamide"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-33-carbamazepine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-33-carbamazepine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-33-carbamazepine\"> </a><p>Co-administration with carbamazepine (Anticonvulsant) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "carbamazepine",
"display": "carbamazepine"
}
],
"text": "Anticonvulsant: carbamazepine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-34-phenobarbital",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-34-phenobarbital",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-34-phenobarbital\"> </a><p>Co-administration with phenobarbital (Anticonvulsant) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "phenobarbital",
"display": "phenobarbital"
}
],
"text": "Anticonvulsant: phenobarbital"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-35-primidone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-35-primidone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-35-primidone\"> </a><p>Co-administration with primidone (Anticonvulsant) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "primidone",
"display": "primidone"
}
],
"text": "Anticonvulsant: primidone"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-36-phenytoin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-36-phenytoin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-36-phenytoin\"> </a><p>Co-administration with phenytoin (Anticonvulsant) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "phenytoin",
"display": "phenytoin"
}
],
"text": "Anticonvulsant: phenytoin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-37-rifampin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-37-rifampin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-37-rifampin\"> </a><p>Co-administration with rifampin (Antimycobacterials) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "rifampin",
"display": "rifampin"
}
],
"text": "Antimycobacterials: rifampin"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-38-rifapentine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-38-rifapentine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-38-rifapentine\"> </a><p>Co-administration with rifapentine (Antimycobacterials) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "rifapentine",
"display": "rifapentine"
}
],
"text": "Antimycobacterials: rifapentine"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-39-lumacaftor-ivacaftor",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-39-lumacaftor-ivacaftor",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-39-lumacaftor-ivacaftor\"> </a><p>Co-administration with lumacaftor/ivacaftor (Cystic fibrosis transmembrane conductance regulator potentiators) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lumacaftor-ivacaftor",
"display": "lumacaftor/ivacaftor"
}
],
"text": "Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-contra-40-st-john-s-wort-hypericum-perforatum",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-contra-40-st-john-s-wort-hypericum-perforatum",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-contra-40-st-john-s-wort-hypericum-perforatum\"> </a><p>Co-administration with St. John’s Wort (Hypericum perforatum) (Herbal products) is contraindicated.</p></div>"
},
"type": "contraindication",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"contraindication": {
"otherTherapy": [
{
"relationshipType": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-category",
"code": "Contraindicated"
}
]
},
"treatment": {
"concept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "st-john-s-wort-hypericum-perforatum",
"display": "St. John’s Wort (Hypericum perforatum)"
}
],
"text": "Herbal products: St. John’s Wort (Hypericum perforatum)"
}
}
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-01-alfuzosin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-01-alfuzosin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-01-alfuzosin\"> </a><p><b>Alpha 1-adrenoreceptor antagonist</b> (alfuzosin): ↑ alfuzosin. Co-administration contraindicated due to potential hypotension (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "alfuzosin",
"display": "alfuzosin"
}
],
"text": "Alpha 1-adrenoreceptor antagonist: alfuzosin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ alfuzosin"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential hypotension (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-02-tamsulosin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-02-tamsulosin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-02-tamsulosin\"> </a><p><b>Alpha 1-adrenoreceptor antagonist</b> (tamsulosin): ↑ tamsulosin. Avoid concomitant use with PAXLOVID.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "tamsulosin",
"display": "tamsulosin"
}
],
"text": "Alpha 1-adrenoreceptor antagonist: tamsulosin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ tamsulosin"
}
},
"management": [
{
"text": "Avoid concomitant use with PAXLOVID."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-03-ranolazine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-03-ranolazine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-03-ranolazine\"> </a><p><b>Antianginal</b> (ranolazine): ↑ ranolazine. Co-administration contraindicated due to potential for serious and/or life-threatening reactions (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ranolazine",
"display": "ranolazine"
}
],
"text": "Antianginal: ranolazine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ ranolazine"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for serious and/or life-threatening reactions (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-04-amiodarone-dronedarone-flecainide-propafenone-qu",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-04-amiodarone-dronedarone-flecainide-propafenone-qu",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-04-amiodarone-dronedarone-flecainide-propafenone-qu\"> </a><p><b>Antiarrhythmics</b> (amiodarone, dronedarone, flecainide, propafenone, quinidine): ↑ antiarrhythmic. Co-administration contraindicated due to potential for cardiac arrhythmias (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "amiodarone-dronedarone-flecainide-propafenone-qu",
"display": "amiodarone, dronedarone, flecainide, propafenone, quinidine"
}
],
"text": "Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ antiarrhythmic"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for cardiac arrhythmias (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-05-lidocaine-systemic-disopyramide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-05-lidocaine-systemic-disopyramide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-05-lidocaine-systemic-disopyramide\"> </a><p><b>Antiarrhythmics</b> (lidocaine (systemic), disopyramide): ↑ antiarrhythmic. Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lidocaine-systemic-disopyramide",
"display": "lidocaine (systemic), disopyramide"
}
],
"text": "Antiarrhythmics: lidocaine (systemic), disopyramide"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ antiarrhythmic"
}
},
"management": [
{
"text": "Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-06-apalutamide-enzalutamide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-06-apalutamide-enzalutamide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-06-apalutamide-enzalutamide\"> </a><p><b>Anticancer drugs</b> (apalutamide, enzalutamide): ↓ nirmatrelvir/ritonavir. Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "apalutamide-enzalutamide",
"display": "apalutamide, enzalutamide"
}
],
"text": "Anticancer drugs: apalutamide, enzalutamide"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-07-abemaciclib-ceritinib-dasatinib-encorafenib-ibru",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-07-abemaciclib-ceritinib-dasatinib-encorafenib-ibru",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-07-abemaciclib-ceritinib-dasatinib-encorafenib-ibru\"> </a><p><b>Anticancer drugs</b> (abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine): ↑ anticancer drug. Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib. Co-administration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to the individual product label for anticancer drug.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "abemaciclib-ceritinib-dasatinib-encorafenib-ibru",
"display": "abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine"
}
],
"text": "Anticancer drugs: abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ anticancer drug"
}
},
"management": [
{
"text": "Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib. Co-administration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to the individual product label for anticancer drug."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-08-warfarin-rivaroxaban-dabigatrana-apixaban",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-08-warfarin-rivaroxaban-dabigatrana-apixaban",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-08-warfarin-rivaroxaban-dabigatrana-apixaban\"> </a><p><b>Anticoagulants</b> (warfarin rivaroxaban dabigatrana apixaban): ↑↓ warfarin ↑ rivaroxaban ↑ dabigatran ↑ apixaban. Closely monitor INR if co-administration with warfarin is necessary. Increased bleeding risk with rivaroxaban. Avoid concomitant use. Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for co-administration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "warfarin-rivaroxaban-dabigatrana-apixaban",
"display": "warfarin rivaroxaban dabigatrana apixaban"
}
],
"text": "Anticoagulants: warfarin rivaroxaban dabigatrana apixaban"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑↓ warfarin ↑ rivaroxaban ↑ dabigatran ↑ apixaban"
}
},
"management": [
{
"text": "Closely monitor INR if co-administration with warfarin is necessary. Increased bleeding risk with rivaroxaban. Avoid concomitant use. Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for co-administration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-09-carbamazepinea-phenobarbital-phenytoin-primidone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-09-carbamazepinea-phenobarbital-phenytoin-primidone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-09-carbamazepinea-phenobarbital-phenytoin-primidone\"> </a><p><b>Anticonvulsants</b> (carbamazepinea, phenobarbital, phenytoin, primidone): ↓ nirmatrelvir/ritonavir. Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "carbamazepinea-phenobarbital-phenytoin-primidone",
"display": "carbamazepinea, phenobarbital, phenytoin, primidone"
}
],
"text": "Anticonvulsants: carbamazepinea, phenobarbital, phenytoin, primidone"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-10-clonazepam",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-10-clonazepam",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-10-clonazepam\"> </a><p><b>Anticonvulsants</b> (clonazepam): ↑ anticonvulsant. A dose decrease may be needed for clonazepam when co-administered with PAXLOVID and clinical monitoring is recommended.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "clonazepam",
"display": "clonazepam"
}
],
"text": "Anticonvulsants: clonazepam"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ anticonvulsant"
}
},
"management": [
{
"text": "A dose decrease may be needed for clonazepam when co-administered with PAXLOVID and clinical monitoring is recommended."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-11-bupropion-trazodone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-11-bupropion-trazodone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-11-bupropion-trazodone\"> </a><p><b>Antidepressants</b> (bupropion trazodone): ↓ bupropion and active metabolite hydroxy-bupropion ↑ trazodone. Monitor for an adequate clinical response to bupropion. Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following co-administration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to the trazadone product label for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "bupropion-trazodone",
"display": "bupropion trazodone"
}
],
"text": "Antidepressants: bupropion trazodone"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ bupropion and active metabolite hydroxy-bupropion ↑ trazodone"
}
},
"management": [
{
"text": "Monitor for an adequate clinical response to bupropion. Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following co-administration of trazodone and ritonavir. A lower dose of trazodone should be considered. Refer to the trazadone product label for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-12-voriconazole-ketoconazole-isavuconazonium-sulfat",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-12-voriconazole-ketoconazole-isavuconazonium-sulfat",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-12-voriconazole-ketoconazole-isavuconazonium-sulfat\"> </a><p><b>Antifungals</b> (voriconazole ketoconazole, isavuconazonium sulfate, itraconazolea): ↓ voriconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole ↑ nirmatrelvir/ritonavir. Avoid concomitant use of voriconazole. Refer to the ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "voriconazole-ketoconazole-isavuconazonium-sulfat",
"display": "voriconazole ketoconazole, isavuconazonium sulfate, itraconazolea"
}
],
"text": "Antifungals: voriconazole ketoconazole, isavuconazonium sulfate, itraconazolea"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ voriconazole ↑ ketoconazole ↑ isavuconazonium sulfate ↑ itraconazole ↑ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Avoid concomitant use of voriconazole. Refer to the ketoconazole, isavuconazonium sulfate, and itraconazole product labels for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-13-colchicine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-13-colchicine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-13-colchicine\"> </a><p><b>Anti-gout</b> (colchicine): ↑ colchicine. Co-administration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "colchicine",
"display": "colchicine"
}
],
"text": "Anti-gout: colchicine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ colchicine"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-14-atazanavir-darunavir-tipranavir",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-14-atazanavir-darunavir-tipranavir",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-14-atazanavir-darunavir-tipranavir\"> </a><p><b>Anti-HIV protease inhibitors</b> (atazanavir, darunavir, tipranavir): ↑ protease inhibitor. For further information, refer to the respective protease inhibitors’ product labels. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events (see section 4.2).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "atazanavir-darunavir-tipranavir",
"display": "atazanavir, darunavir, tipranavir"
}
],
"text": "Anti-HIV protease inhibitors: atazanavir, darunavir, tipranavir"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ protease inhibitor"
}
},
"management": [
{
"text": "For further information, refer to the respective protease inhibitors’ product labels. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or protease inhibitor adverse events (see section 4.2)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-15-efavirenz-maraviroc-nevirapine-zidovudine-bicteg",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-15-efavirenz-maraviroc-nevirapine-zidovudine-bicteg",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-15-efavirenz-maraviroc-nevirapine-zidovudine-bicteg\"> </a><p><b>Anti-HIV</b> (efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir): ↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir. For further information, refer to the respective anti-HIV drugs’ product label.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "efavirenz-maraviroc-nevirapine-zidovudine-bicteg",
"display": "efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir"
}
],
"text": "Anti-HIV: efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir"
}
},
"management": [
{
"text": "For further information, refer to the respective anti-HIV drugs’ product label."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-16-clarithromycin-erythromycin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-16-clarithromycin-erythromycin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-16-clarithromycin-erythromycin\"> </a><p><b>Anti-infective</b> (clarithromycin, erythromycin): ↑ clarithromycin ↑ erythromycin. Refer to the respective product label for anti-infective dose adjustment.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "clarithromycin-erythromycin",
"display": "clarithromycin, erythromycin"
}
],
"text": "Anti-infective: clarithromycin, erythromycin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ clarithromycin ↑ erythromycin"
}
},
"management": [
{
"text": "Refer to the respective product label for anti-infective dose adjustment."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-17-rifampin-rifapentine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-17-rifampin-rifapentine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-17-rifampin-rifapentine\"> </a><p><b>Antimycobacterial</b> (rifampin, rifapentine): ↓ nirmatrelvir/ritonavir. Co-administration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "rifampin-rifapentine",
"display": "rifampin, rifapentine"
}
],
"text": "Antimycobacterial: rifampin, rifapentine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential loss of virologic response and possible resistance. Alternate antimycobacterial drugs such as rifabutin should be considered (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-18-bedaquiline-rifabutin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-18-bedaquiline-rifabutin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-18-bedaquiline-rifabutin\"> </a><p><b>Antimycobacterial</b> (bedaquiline rifabutin): ↑ bedaquiline ↑ rifabutin. Refer to the bedaquiline product label for further information. Refer to the rifabutin product label for further information on rifabutin dose reduction.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "bedaquiline-rifabutin",
"display": "bedaquiline rifabutin"
}
],
"text": "Antimycobacterial: bedaquiline rifabutin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ bedaquiline ↑ rifabutin"
}
},
"management": [
{
"text": "Refer to the bedaquiline product label for further information. Refer to the rifabutin product label for further information on rifabutin dose reduction."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-19-albendazole",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-19-albendazole",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-19-albendazole\"> </a><p><b>Antiparasitic agent</b> (albendazole): ↓ albendazole. Significant decreases in plasma concentrations of albendazole and its active metabolite may occur due to induction by ritonavir, with a risk of decreased albendazole efficacy. Clinical monitoring of therapeutic response and possible adjustment of albendazole dosage during treatment with PAXLOVID and following discontinuation is recommended.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "albendazole",
"display": "albendazole"
}
],
"text": "Antiparasitic agent: albendazole"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ albendazole"
}
},
"management": [
{
"text": "Significant decreases in plasma concentrations of albendazole and its active metabolite may occur due to induction by ritonavir, with a risk of decreased albendazole efficacy. Clinical monitoring of therapeutic response and possible adjustment of albendazole dosage during treatment with PAXLOVID and following discontinuation is recommended."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-20-lurasidone-pimozide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-20-lurasidone-pimozide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-20-lurasidone-pimozide\"> </a><p><b>Antipsychotics</b> (lurasidone, pimozide): ↑ lurasidone ↑ pimozide. Co-administration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lurasidone-pimozide",
"display": "lurasidone, pimozide"
}
],
"text": "Antipsychotics: lurasidone, pimozide"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ lurasidone ↑ pimozide"
}
},
"management": [
{
"text": "Co-administration contraindicated due to serious and/or life-threatening reactions such as cardiac arrhythmias (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-21-quetiapine-clozapine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-21-quetiapine-clozapine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-21-quetiapine-clozapine\"> </a><p><b>Antipsychotics</b> (quetiapine clozapine): ↑ quetiapine ↑ clozapine. If co-administration is necessary, reduce quetiapine dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine product label for recommendations. If co-administration is necessary, consider reducing the clozapine dose and monitor for adverse reactions.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "quetiapine-clozapine",
"display": "quetiapine clozapine"
}
],
"text": "Antipsychotics: quetiapine clozapine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ quetiapine ↑ clozapine"
}
},
"management": [
{
"text": "If co-administration is necessary, reduce quetiapine dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine product label for recommendations. If co-administration is necessary, consider reducing the clozapine dose and monitor for adverse reactions."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-22-silodosin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-22-silodosin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-22-silodosin\"> </a><p><b>Benign prostatic hyperplasia agents</b> (silodosin): ↑ silodosin. Co-administration contraindicated due to potential for postural hypotension (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "silodosin",
"display": "silodosin"
}
],
"text": "Benign prostatic hyperplasia agents: silodosin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ silodosin"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for postural hypotension (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-23-amlodipine-diltiazem-felodipine-nicardipine-nife",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-23-amlodipine-diltiazem-felodipine-nicardipine-nife",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-23-amlodipine-diltiazem-felodipine-nicardipine-nife\"> </a><p><b>Calcium channel blockers</b> (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil): ↑ calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with PAXLOVID. If co-administered, refer to the individual product label for calcium channel blocker for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "amlodipine-diltiazem-felodipine-nicardipine-nife",
"display": "amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil"
}
],
"text": "Calcium channel blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ calcium channel blocker"
}
},
"management": [
{
"text": "Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with PAXLOVID. If co-administered, refer to the individual product label for calcium channel blocker for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-24-digoxin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-24-digoxin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-24-digoxin\"> </a><p><b>Cardiac glycosides</b> (digoxin): ↑ digoxin. Caution should be exercised when co-administering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels. Refer to the digoxin product label for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "digoxin",
"display": "digoxin"
}
],
"text": "Cardiac glycosides: digoxin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ digoxin"
}
},
"management": [
{
"text": "Caution should be exercised when co-administering PAXLOVID with digoxin, with appropriate monitoring of serum digoxin levels. Refer to the digoxin product label for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-25-eplerenone-ivabradine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-25-eplerenone-ivabradine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-25-eplerenone-ivabradine\"> </a><p><b>Cardiovascular agents</b> (eplerenone ivabradine): ↑ eplerenone ↑ ivabradine. Co-administration with eplerenone is contraindicated due to potential for hyperkalemia (see section 4.3). Co-administration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "eplerenone-ivabradine",
"display": "eplerenone ivabradine"
}
],
"text": "Cardiovascular agents: eplerenone ivabradine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ eplerenone ↑ ivabradine"
}
},
"management": [
{
"text": "Co-administration with eplerenone is contraindicated due to potential for hyperkalemia (see section 4.3). Co-administration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-26-aliskiren-ticagrelor-vorapaxar-clopidogrel-cilos",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-26-aliskiren-ticagrelor-vorapaxar-clopidogrel-cilos",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-26-aliskiren-ticagrelor-vorapaxar-clopidogrel-cilos\"> </a><p><b>Cardiovascular agents</b> (aliskiren, ticagrelor, vorapaxar clopidogrel cilostazol mavacamten): ↑ aliskiren ↑ ticagrelor ↑ vorapaxar ↓ clopidogrel active metabolite ↑ cilostazol ↑ mavacamten. Avoid concomitant use with PAXLOVID. Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information. Co-administration with mavacamten may increase mavacamten plasma concentration and increase the risk of heart failure. Discontinue mavacamten for the duration of PAXLOVID treatment. Resumption of mavacamten within 5 days of completing PAXLOVID may result in higher exposure of mavacamten. Refer to the mavacamten product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "aliskiren-ticagrelor-vorapaxar-clopidogrel-cilos",
"display": "aliskiren, ticagrelor, vorapaxar clopidogrel cilostazol mavacamten"
}
],
"text": "Cardiovascular agents: aliskiren, ticagrelor, vorapaxar clopidogrel cilostazol mavacamten"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ aliskiren ↑ ticagrelor ↑ vorapaxar ↓ clopidogrel active metabolite ↑ cilostazol ↑ mavacamten"
}
},
"management": [
{
"text": "Avoid concomitant use with PAXLOVID. Dosage adjustment of cilostazol is recommended. Refer to the cilostazol product label for more information. Co-administration with mavacamten may increase mavacamten plasma concentration and increase the risk of heart failure. Discontinue mavacamten for the duration of PAXLOVID treatment. Resumption of mavacamten within 5 days of completing PAXLOVID may result in higher exposure of mavacamten. Refer to the mavacamten product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-27-betamethasone-budesonide-ciclesonide-dexamethaso",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-27-betamethasone-budesonide-ciclesonide-dexamethaso",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-27-betamethasone-budesonide-ciclesonide-dexamethaso\"> </a><p><b>Corticosteroids primarily metabolized by CYP3A</b> (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone): ↑ corticosteroid. Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A4 inhibitor is low. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "betamethasone-budesonide-ciclesonide-dexamethaso",
"display": "betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone"
}
],
"text": "Corticosteroids primarily metabolized by CYP3A: betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ corticosteroid"
}
},
"management": [
{
"text": "Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. However, the risk of Cushing’s syndrome and adrenal suppression associated with short-term use of a strong CYP3A4 inhibitor is low. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone should be considered."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-28-lumacaftor-ivacaftor",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-28-lumacaftor-ivacaftor",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-28-lumacaftor-ivacaftor\"> </a><p><b>Cystic fibrosis transmembrane conductance regulator potentiators</b> (lumacaftor/ivacaftor): ↓ nirmatrelvir/ritonavir. Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lumacaftor-ivacaftor",
"display": "lumacaftor/ivacaftor"
}
],
"text": "Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-29-ivacaftor-elexacaftor-tezacaftor-ivacaftor-tezac",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-29-ivacaftor-elexacaftor-tezacaftor-ivacaftor-tezac",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-29-ivacaftor-elexacaftor-tezacaftor-ivacaftor-tezac\"> </a><p><b>Cystic fibrosis transmembrane conductance regulator potentiators</b> (ivacaftor elexacaftor/ tezacaftor/ivacaftor tezacaftor/ivacaftor): ↑ ivacaftor ↑ elexacaftor/ tezacaftor/ivacaftor ↑ tezacaftor/ivacaftor. Reduce dosage when co-administered with PAXLOVID. Refer to the individual product labels for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ivacaftor-elexacaftor-tezacaftor-ivacaftor-tezac",
"display": "ivacaftor elexacaftor/ tezacaftor/ivacaftor tezacaftor/ivacaftor"
}
],
"text": "Cystic fibrosis transmembrane conductance regulator potentiators: ivacaftor elexacaftor/ tezacaftor/ivacaftor tezacaftor/ivacaftor"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ ivacaftor ↑ elexacaftor/ tezacaftor/ivacaftor ↑ tezacaftor/ivacaftor"
}
},
"management": [
{
"text": "Reduce dosage when co-administered with PAXLOVID. Refer to the individual product labels for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-30-saxagliptin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-30-saxagliptin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-30-saxagliptin\"> </a><p><b>Dipeptidyl peptidase 4 (DPP4) inhibitors</b> (saxagliptin): ↑ saxagliptin. Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "saxagliptin",
"display": "saxagliptin"
}
],
"text": "Dipeptidyl peptidase 4 (DPP4) inhibitors: saxagliptin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ saxagliptin"
}
},
"management": [
{
"text": "Dosage adjustment of saxagliptin is recommended. Refer to the saxagliptin product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-31-bosentan",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-31-bosentan",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-31-bosentan\"> </a><p><b>Endothelin receptor antagonists</b> (bosentan): ↑ bosentan. Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Refer to the bosentan product label for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "bosentan",
"display": "bosentan"
}
],
"text": "Endothelin receptor antagonists: bosentan"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ bosentan"
}
},
"management": [
{
"text": "Discontinue use of bosentan at least 36 hours prior to initiation of PAXLOVID. Refer to the bosentan product label for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-32-dihydroergotamine-ergotamine-methylergonovine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-32-dihydroergotamine-ergotamine-methylergonovine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-32-dihydroergotamine-ergotamine-methylergonovine\"> </a><p><b>Ergot derivatives</b> (dihydroergotamine, ergotamine, methylergonovine): ↑ dihydroergotamine ↑ ergotamine ↑ methylergonovine. Co-administration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "dihydroergotamine-ergotamine-methylergonovine",
"display": "dihydroergotamine, ergotamine, methylergonovine"
}
],
"text": "Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ dihydroergotamine ↑ ergotamine ↑ methylergonovine"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-33-elbasvir-grazoprevir-glecaprevir-pibrentasvir-om",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-33-elbasvir-grazoprevir-glecaprevir-pibrentasvir-om",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-33-elbasvir-grazoprevir-glecaprevir-pibrentasvir-om\"> </a><p><b>Hepatitis C direct acting antivirals</b> (elbasvir/grazoprevir, glecaprevir/ pibrentasvir ombitasvir/ paritaprevir/ritonavir and dasabuvir sofosbuvir/ velpatasvir/ voxilaprevir): ↑ antiviral. Increased grazoprevir concentrations can result in ALT elevations. Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID. Refer to the ombitasvir/paritaprevir/ ritonavir and dasabuvir label for further information. Refer to the sofosbuvir/velpatasvir/ voxilaprevir product label for further information. Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use (see section 4.2).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "elbasvir-grazoprevir-glecaprevir-pibrentasvir-om",
"display": "elbasvir/grazoprevir, glecaprevir/ pibrentasvir ombitasvir/ paritaprevir/ritonavir and dasabuvir sofosbuvir/ velpatasvir/ voxilaprevir"
}
],
"text": "Hepatitis C direct acting antivirals: elbasvir/grazoprevir, glecaprevir/ pibrentasvir ombitasvir/ paritaprevir/ritonavir and dasabuvir sofosbuvir/ velpatasvir/ voxilaprevir"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ antiviral"
}
},
"management": [
{
"text": "Increased grazoprevir concentrations can result in ALT elevations. Avoid concomitant use of glecaprevir/pibrentasvir with PAXLOVID. Refer to the ombitasvir/paritaprevir/ ritonavir and dasabuvir label for further information. Refer to the sofosbuvir/velpatasvir/ voxilaprevir product label for further information. Patients on ritonavir-containing HCV regimens should continue their treatment as indicated. Monitor for increased PAXLOVID or HCV drug adverse events with concomitant use (see section 4.2)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-34-st-john-s-wort-hypericum-perforatum",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-34-st-john-s-wort-hypericum-perforatum",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-34-st-john-s-wort-hypericum-perforatum\"> </a><p><b>Herbal products</b> (St. John’s Wort (Hypericum perforatum)): ↓ nirmatrelvir/ritonavir. Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "st-john-s-wort-hypericum-perforatum",
"display": "St. John’s Wort (Hypericum perforatum)"
}
],
"text": "Herbal products: St. John’s Wort (Hypericum perforatum)"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ nirmatrelvir/ritonavir"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-35-lovastatin-simvastatin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-35-lovastatin-simvastatin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-35-lovastatin-simvastatin\"> </a><p><b>HMG-CoA reductase inhibitors</b> (lovastatin, simvastatin): ↑ lovastatin ↑ simvastatin. Co-administration contraindicated due to potential for myopathy including rhabdomyolysis (see section 4.3). Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment and for 5 days after completing PAXLOVID.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lovastatin-simvastatin",
"display": "lovastatin, simvastatin"
}
],
"text": "HMG-CoA reductase inhibitors: lovastatin, simvastatin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ lovastatin ↑ simvastatin"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for myopathy including rhabdomyolysis (see section 4.3). Discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment and for 5 days after completing PAXLOVID."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-36-atorvastatin-rosuvastatina",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-36-atorvastatin-rosuvastatina",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-36-atorvastatin-rosuvastatina\"> </a><p><b>HMG-CoA reductase inhibitors</b> (atorvastatin, rosuvastatina): ↑ atorvastatin ↑ rosuvastatin. Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be held prior to or after completing PAXLOVID.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "atorvastatin-rosuvastatina",
"display": "atorvastatin, rosuvastatina"
}
],
"text": "HMG-CoA reductase inhibitors: atorvastatin, rosuvastatina"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ atorvastatin ↑ rosuvastatin"
}
},
"management": [
{
"text": "Consider temporary discontinuation of atorvastatin and rosuvastatin during treatment with PAXLOVID. Atorvastatin and rosuvastatin do not need to be held prior to or after completing PAXLOVID."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-37-ethinyl-estradiol",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-37-ethinyl-estradiol",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-37-ethinyl-estradiol\"> </a><p><b>Hormonal contraceptive</b> (ethinyl estradiol): ↓ ethinyl estradiol. An additional, non-hormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "ethinyl-estradiol",
"display": "ethinyl estradiol"
}
],
"text": "Hormonal contraceptive: ethinyl estradiol"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↓ ethinyl estradiol"
}
},
"management": [
{
"text": "An additional, non-hormonal method of contraception should be considered during the 5 days of PAXLOVID treatment and until one menstrual cycle after stopping PAXLOVID."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-38-voclosporin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-38-voclosporin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-38-voclosporin\"> </a><p><b>Immunosuppressants</b> (voclosporin): ↑ voclosporin. Co-administration contraindicated due to potential for acute and/or chronic nephrotoxicity (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "voclosporin",
"display": "voclosporin"
}
],
"text": "Immunosuppressants: voclosporin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ voclosporin"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for acute and/or chronic nephrotoxicity (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-39-calcineurin-inhibitors-cyclosporine-tacrolimus-m",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-39-calcineurin-inhibitors-cyclosporine-tacrolimus-m",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-39-calcineurin-inhibitors-cyclosporine-tacrolimus-m\"> </a><p><b>Immunosuppressants</b> (Calcineurin inhibitors: cyclosporine, tacrolimus mTOR inhibitors: everolimus, sirolimus): ↑ cyclosporine ↑ tacrolimus ↑ everolimus ↑ sirolimus. Avoid concomitant use of calcineurin inhibitors and mTOR inhibitors during treatment with PAXLOVID. If the co-administration cannot be avoided, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and immunosuppressant-associated adverse reactions are recommended during and after treatment with PAXLOVID. Refer to the individual immunosuppressant product label and latest guidelines for further information and obtain expert consultation of a multidisciplinary group (see section 4.4).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "calcineurin-inhibitors-cyclosporine-tacrolimus-m",
"display": "Calcineurin inhibitors: cyclosporine, tacrolimus mTOR inhibitors: everolimus, sirolimus"
}
],
"text": "Immunosuppressants: Calcineurin inhibitors: cyclosporine, tacrolimus mTOR inhibitors: everolimus, sirolimus"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ cyclosporine ↑ tacrolimus ↑ everolimus ↑ sirolimus"
}
},
"management": [
{
"text": "Avoid concomitant use of calcineurin inhibitors and mTOR inhibitors during treatment with PAXLOVID. If the co-administration cannot be avoided, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and immunosuppressant-associated adverse reactions are recommended during and after treatment with PAXLOVID. Refer to the individual immunosuppressant product label and latest guidelines for further information and obtain expert consultation of a multidisciplinary group (see section 4.4)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-40-tofacitinib-upadacitinib",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-40-tofacitinib-upadacitinib",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-40-tofacitinib-upadacitinib\"> </a><p><b>Janus kinase (JAK) inhibitors</b> (tofacitinib upadacitinib): ↑ tofacitinib ↑ upadacitinib. Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information. Dosing recommendations for co‑administration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "tofacitinib-upadacitinib",
"display": "tofacitinib upadacitinib"
}
],
"text": "Janus kinase (JAK) inhibitors: tofacitinib upadacitinib"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ tofacitinib ↑ upadacitinib"
}
},
"management": [
{
"text": "Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib product label for more information. Dosing recommendations for co‑administration of upadacitinib with PAXLOVID depends on the upadacitinib indication. Refer to the upadacitinib product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-41-salmeterol",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-41-salmeterol",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-41-salmeterol\"> </a><p><b>Long-acting beta-adrenoceptor agonist</b> (salmeterol): ↑ salmeterol. Avoid concomitant use with PAXLOVID. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "salmeterol",
"display": "salmeterol"
}
],
"text": "Long-acting beta-adrenoceptor agonist: salmeterol"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ salmeterol"
}
},
"management": [
{
"text": "Avoid concomitant use with PAXLOVID. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-42-lomitapide",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-42-lomitapide",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-42-lomitapide\"> </a><p><b>Microsomal triglyceride transfer protein (MTTP) inhibitor</b> (lomitapide): ↑ lomitapide. Co-administration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "lomitapide",
"display": "lomitapide"
}
],
"text": "Microsomal triglyceride transfer protein (MTTP) inhibitor: lomitapide"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ lomitapide"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for hepatotoxicity and gastrointestinal adverse reactions (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-43-eletriptan-ubrogepant",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-43-eletriptan-ubrogepant",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-43-eletriptan-ubrogepant\"> </a><p><b>Migraine medications</b> (eletriptan ubrogepant): ↑ eletriptan ↑ ubrogepant. Co-administration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events (see section 4.3). Co-administration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "eletriptan-ubrogepant",
"display": "eletriptan ubrogepant"
}
],
"text": "Migraine medications: eletriptan ubrogepant"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ eletriptan ↑ ubrogepant"
}
},
"management": [
{
"text": "Co-administration of eletriptan within at least 72 hours of PAXLOVID is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events (see section 4.3). Co-administration of ubrogepant with PAXLOVID is contraindicated due to potential for serious adverse reactions (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-44-rimegepant",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-44-rimegepant",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-44-rimegepant\"> </a><p><b>Migraine medications</b> (rimegepant): ↑ rimegepant. Avoid concomitant use with PAXLOVID.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "rimegepant",
"display": "rimegepant"
}
],
"text": "Migraine medications: rimegepant"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ rimegepant"
}
},
"management": [
{
"text": "Avoid concomitant use with PAXLOVID."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-45-finerenone",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-45-finerenone",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-45-finerenone\"> </a><p><b>Mineralocorticoid receptor antagonists</b> (finerenone): ↑ finerenone. Co-administration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "finerenone",
"display": "finerenone"
}
],
"text": "Mineralocorticoid receptor antagonists: finerenone"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ finerenone"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-46-darifenacin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-46-darifenacin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-46-darifenacin\"> </a><p><b>Muscarinic receptor antagonists</b> (darifenacin): ↑ darifenacin. The darifenacin daily dose should not exceed 7.5 mg when co-administered with PAXLOVID. Refer to the darifenacin product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "darifenacin",
"display": "darifenacin"
}
],
"text": "Muscarinic receptor antagonists: darifenacin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ darifenacin"
}
},
"management": [
{
"text": "The darifenacin daily dose should not exceed 7.5 mg when co-administered with PAXLOVID. Refer to the darifenacin product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-47-fentanyl-hydrocodone-oxycodone-meperidine-methad",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-47-fentanyl-hydrocodone-oxycodone-meperidine-methad",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-47-fentanyl-hydrocodone-oxycodone-meperidine-methad\"> </a><p><b>Narcotic analgesics</b> (fentanyl, hydrocodone, oxycodone, meperidine methadone): ↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine ↓ methadone. Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. Refer to the individual product label for more information. Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "fentanyl-hydrocodone-oxycodone-meperidine-methad",
"display": "fentanyl, hydrocodone, oxycodone, meperidine methadone"
}
],
"text": "Narcotic analgesics: fentanyl, hydrocodone, oxycodone, meperidine methadone"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine ↓ methadone"
}
},
"management": [
{
"text": "Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID. If concomitant use with PAXLOVID is necessary, consider a dosage reduction of the narcotic analgesic and monitor patients closely at frequent intervals. Refer to the individual product label for more information. Monitor methadone-maintained patients closely for evidence of withdrawal effects and adjust the methadone dose accordingly."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-48-suvorexant-aripiprazole-brexpiprazole-cariprazin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-48-suvorexant-aripiprazole-brexpiprazole-cariprazin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-48-suvorexant-aripiprazole-brexpiprazole-cariprazin\"> </a><p><b>Neuropsychiatric agents</b> (suvorexant aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin): ↑ suvorexant ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin. Avoid concomitant use of suvorexant with PAXLOVID. Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to the individual product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "suvorexant-aripiprazole-brexpiprazole-cariprazin",
"display": "suvorexant aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin"
}
],
"text": "Neuropsychiatric agents: suvorexant aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, pimavanserin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ suvorexant ↑ aripiprazole ↑ brexpiprazole ↑ cariprazine ↑ iloperidone ↑ lumateperone ↑ pimavanserin"
}
},
"management": [
{
"text": "Avoid concomitant use of suvorexant with PAXLOVID. Dosage adjustment of aripiprazole, brexpiprazole, cariprazine, iloperidone, lumateperone, and pimavanserin is recommended. Refer to the individual product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-49-suzetrigine",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-49-suzetrigine",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-49-suzetrigine\"> </a><p><b>Non-opioid analgesic (selective blocker of Nav1.8 sodium channels)</b> (suzetrigine): ↑ suzetrigine and active metabolite M6-SUZ. Co-administration contraindicated due to potential for serious and/or life-threatening suzetrigine adverse reactions (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "suzetrigine",
"display": "suzetrigine"
}
],
"text": "Non-opioid analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ suzetrigine and active metabolite M6-SUZ"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for serious and/or life-threatening suzetrigine adverse reactions (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-50-sildenafil",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-50-sildenafil",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-50-sildenafil\"> </a><p><b>Pulmonary hypertension agents (PDE5 inhibitors)</b> (sildenafil): ↑ sildenafil. Co-administration of sildenafil with PAXLOVID is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "sildenafil",
"display": "sildenafil"
}
],
"text": "Pulmonary hypertension agents (PDE5 inhibitors): sildenafil"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ sildenafil"
}
},
"management": [
{
"text": "Co-administration of sildenafil with PAXLOVID is contraindicated due to the potential for sildenafil associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-51-tadalafil-riociguat",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-51-tadalafil-riociguat",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-51-tadalafil-riociguat\"> </a><p><b>Pulmonary hypertension agents (PDE5 inhibitors) Pulmonary hypertension agents (sGC stimulators)</b> (tadalafil riociguat): ↑ tadalafil ↑ riociguat. Avoid concomitant use of tadalafil with PAXLOVID. Dosage adjustment is recommended for riociguat. Refer to the riociguat product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "tadalafil-riociguat",
"display": "tadalafil riociguat"
}
],
"text": "Pulmonary hypertension agents (PDE5 inhibitors) Pulmonary hypertension agents (sGC stimulators): tadalafil riociguat"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ tadalafil ↑ riociguat"
}
},
"management": [
{
"text": "Avoid concomitant use of tadalafil with PAXLOVID. Dosage adjustment is recommended for riociguat. Refer to the riociguat product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-52-avanafil-sildenafil-tadalafil-vardenafil",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-52-avanafil-sildenafil-tadalafil-vardenafil",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-52-avanafil-sildenafil-tadalafil-vardenafil\"> </a><p><b>Erectile dysfunction agents (PDE5 inhibitors)</b> (avanafil sildenafil, tadalafil, vardenafil): ↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil. Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established. Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID. Refer to the individual product label for more information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "avanafil-sildenafil-tadalafil-vardenafil",
"display": "avanafil sildenafil, tadalafil, vardenafil"
}
],
"text": "Erectile dysfunction agents (PDE5 inhibitors): avanafil sildenafil, tadalafil, vardenafil"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil"
}
},
"management": [
{
"text": "Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established. Dosage adjustment is recommended for use of sildenafil, tadalafil, or vardenafil with PAXLOVID. Refer to the individual product label for more information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-53-naloxegol",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-53-naloxegol",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-53-naloxegol\"> </a><p><b>Opioid antagonists</b> (naloxegol): ↑ naloxegol. Co-administration contraindicated due to the potential for opioid withdrawal symptoms (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "naloxegol",
"display": "naloxegol"
}
],
"text": "Opioid antagonists: naloxegol"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ naloxegol"
}
},
"management": [
{
"text": "Co-administration contraindicated due to the potential for opioid withdrawal symptoms (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-54-triazolam-oral-midazolama",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-54-triazolam-oral-midazolama",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-54-triazolam-oral-midazolama\"> </a><p><b>Sedative/hypnotics</b> (triazolam, oral midazolama): ↑ triazolam ↑ midazolam. Co-administration contraindicated due to potential for extreme sedation and respiratory depression (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "triazolam-oral-midazolama",
"display": "triazolam, oral midazolama"
}
],
"text": "Sedative/hypnotics: triazolam, oral midazolama"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ triazolam ↑ midazolam"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for extreme sedation and respiratory depression (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-55-buspirone-clorazepate-diazepam-estazolam-fluraze",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-55-buspirone-clorazepate-diazepam-estazolam-fluraze",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-55-buspirone-clorazepate-diazepam-estazolam-fluraze\"> </a><p><b>Sedative/hypnotics</b> (buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem midazolam (administered parenterally)): ↑ sedative/hypnotic ↑ midazolam. A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events is recommended. Co-administration of midazolam (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Refer to the midazolam product label for further information.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "buspirone-clorazepate-diazepam-estazolam-fluraze",
"display": "buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem midazolam (administered parenterally)"
}
],
"text": "Sedative/hypnotics: buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem midazolam (administered parenterally)"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ sedative/hypnotic ↑ midazolam"
}
},
"management": [
{
"text": "A dose decrease may be needed for these drugs when co-administered with PAXLOVID and monitoring for adverse events is recommended. Co-administration of midazolam (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Refer to the midazolam product label for further information."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-56-flibanserin",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-56-flibanserin",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-56-flibanserin\"> </a><p><b>Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist</b> (flibanserin): ↑ flibanserin. Co-administration contraindicated due to potential for hypotension, syncope, and CNS depression (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "flibanserin",
"display": "flibanserin"
}
],
"text": "Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist: flibanserin"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ flibanserin"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for hypotension, syncope, and CNS depression (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-57-tolvaptan",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-57-tolvaptan",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-57-tolvaptan\"> </a><p><b>Vasopressin receptor antagonists</b> (tolvaptan): ↑ tolvaptan. Co-administration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see section 4.3).</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "tolvaptan",
"display": "tolvaptan"
}
],
"text": "Vasopressin receptor antagonists: tolvaptan"
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "↑ tolvaptan"
}
},
"management": [
{
"text": "Co-administration contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see section 4.3)."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-int-58-a-see-section-5-2-drug-interaction-studies-condu",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-int-58-a-see-section-5-2-drug-interaction-studies-condu",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-int-58-a-see-section-5-2-drug-interaction-studies-condu\"> </a><p><b>a.\tSee section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.</b> (a.\tSee section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.): a.\tSee section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.. a.\tSee section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.</p></div>"
},
"type": "interaction",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"interaction": {
"interactant": [
{
"itemCodeableConcept": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/draft-substance",
"code": "a-see-section-5-2-drug-interaction-studies-condu",
"display": "a. See section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir."
}
],
"text": "a. See section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir.: a. See section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir."
}
}
],
"type": {
"coding": [
{
"system": "http://hl7.org/fhir/CodeSystem/clinical-use-definition-type",
"code": "interaction"
}
]
},
"effect": {
"concept": {
"text": "a. See section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir."
}
},
"management": [
{
"text": "a. See section 5.2 Drug interaction studies conducted with nirmatrelvir/ritonavir."
}
]
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-warn-interactions",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-warn-interactions",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-warn-interactions\"> </a><p>Risk of serious adverse reactions due to drug interactions</p></div>"
},
"type": "warning",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"warning": {
"description": "Risk of serious adverse reactions due to drug interactions"
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-warn-hypersensitivity",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-warn-hypersensitivity",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-warn-hypersensitivity\"> </a><p>Hypersensitivity reactions including anaphylaxis have been reported</p></div>"
},
"type": "warning",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"warning": {
"description": "Hypersensitivity reactions including anaphylaxis have been reported"
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-warn-hepatotoxicity",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-warn-hepatotoxicity",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-warn-hepatotoxicity\"> </a><p>Hepatotoxicity; caution in pre-existing liver disease</p></div>"
},
"type": "warning",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"warning": {
"description": "Hepatotoxicity; caution in pre-existing liver disease"
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-warn-hiv-resistance",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-warn-hiv-resistance",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-warn-hiv-resistance\"> </a><p>Risk of HIV-1 resistance development in uncontrolled HIV-1 infection</p></div>"
},
"type": "warning",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"warning": {
"description": "Risk of HIV-1 resistance development in uncontrolled HIV-1 infection"
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-01-hypersensitivity",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-01-hypersensitivity",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-01-hypersensitivity\"> </a><p>Hypersensitivity — Immune system disorders (Uncommon ≥1/1,000 to <1/100)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Hypersensitivity"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Immune system disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "uncommon",
"display": "Uncommon ≥1/1,000 to <1/100"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-02-anaphylaxis",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-02-anaphylaxis",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-02-anaphylaxis\"> </a><p>Anaphylaxis — Immune system disorders (Rare ≥1/10,000 to <1/1,000)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Anaphylaxis"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Immune system disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "rare",
"display": "Rare ≥1/10,000 to <1/1,000"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-03-dysgeusiaa-headache",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-03-dysgeusiaa-headache",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-03-dysgeusiaa-headache\"> </a><p>Dysgeusiaa Headache — Nervous system disorders (Common ≥1/100 to <1/10)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Dysgeusiaa Headache"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Nervous system disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "common",
"display": "Common ≥1/100 to <1/10"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-04-hypertension",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-04-hypertension",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-04-hypertension\"> </a><p>Hypertension — Vascular disorders (Uncommon ≥1/1,000 to <1/100)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Hypertension"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Vascular disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "uncommon",
"display": "Uncommon ≥1/1,000 to <1/100"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-05-diarrheaa-nausea",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-05-diarrheaa-nausea",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-05-diarrheaa-nausea\"> </a><p>Diarrheaa Nausea — Gastrointestinal disorders (Common ≥1/100 to <1/10)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Diarrheaa Nausea"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Gastrointestinal disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "common",
"display": "Common ≥1/100 to <1/10"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-06-vomitinga-abdominal-pain",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-06-vomitinga-abdominal-pain",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-06-vomitinga-abdominal-pain\"> </a><p>Vomitinga Abdominal pain — Gastrointestinal disorders (Uncommon ≥1/1,000 to <1/100)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Vomitinga Abdominal pain"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Gastrointestinal disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "uncommon",
"display": "Uncommon ≥1/1,000 to <1/100"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-07-toxic-epidermal-necrolysis-stevens-johnson-syndr",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-07-toxic-epidermal-necrolysis-stevens-johnson-syndr",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-07-toxic-epidermal-necrolysis-stevens-johnson-syndr\"> </a><p>Toxic epidermal necrolysis Stevens-Johnson syndrome — Skin and subcutaneous tissue disorders (Rare ≥1/10,000 to <1/1,000)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Toxic epidermal necrolysis Stevens-Johnson syndrome"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "Skin and subcutaneous tissue disorders"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "rare",
"display": "Rare ≥1/10,000 to <1/1,000"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-08-malaise",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-08-malaise",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-08-malaise\"> </a><p>Malaise — General disorders and administration site conditions (Rare ≥1/10,000 to <1/1,000)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Malaise"
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "General disorders and administration site conditions"
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "rare",
"display": "Rare ≥1/10,000 to <1/1,000"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-09-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-09-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-09-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Very Common ≥1/10)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "very-common",
"display": "Very Common ≥1/10"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-10-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-10-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-10-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Common ≥1/100 to <1/10)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "common",
"display": "Common ≥1/100 to <1/10"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-11-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-11-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-11-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Uncommon ≥1/1,000 to <1/100)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "uncommon",
"display": "Uncommon ≥1/1,000 to <1/100"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-12-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-12-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-12-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Rare ≥1/10,000 to <1/1,000)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "rare",
"display": "Rare ≥1/10,000 to <1/1,000"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-13-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-13-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-13-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Very Rare <1/10,000)</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "very-rare",
"display": "Very Rare <1/10,000"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/ClinicalUseDefinition/cud-ae-14-adverse-drug-reaction-adr-identified-post-market",
"resource": {
"resourceType": "ClinicalUseDefinition",
"id": "cud-ae-14-adverse-drug-reaction-adr-identified-post-market",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"ClinicalUseDefinition_cud-ae-14-adverse-drug-reaction-adr-identified-post-market\"> </a><p>Adverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. — *\tAdverse drug reaction (ADR) identified post-marketing. a.\tOccurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment. (Frequency Not Known (cannot be estimated from the available data))</p></div>"
},
"type": "undesirable-effect",
"subject": [
{
"reference": "MedicinalProductDefinition/mpd-paxlovid"
}
],
"undesirableEffect": {
"symptomConditionEffect": {
"concept": {
"text": "Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
},
"classification": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/soc",
"display": "* Adverse drug reaction (ADR) identified post-marketing. a. Occurring at a ≥1% frequency in the PAXLOVID group and at a greater frequency than in the placebo group and/or likely associated with PAXLOVID based on available data and causality assessment."
}
]
},
"frequencyOfOccurrence": {
"coding": [
{
"system": "https://www.hsa.gov.sg/epi/adr-frequency",
"code": "not-known",
"display": "Frequency Not Known (cannot be estimated from the available data)"
}
]
}
}
}
},
{
"fullUrl": "https://www.hsa.gov.sg/epi/MedicationKnowledge/mk-paxlovid",
"resource": {
"resourceType": "MedicationKnowledge",
"id": "mk-paxlovid",
"text": {
"status": "generated",
"div": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><a name=\"MedicationKnowledge_mk-paxlovid\"> </a><p>PAXLOVID (ATC J05AE30). Standard dose: nirmatrelvir 300 mg + ritonavir 100 mg every 12 hours for 5 days. eGFR 30 to <60 mL/min: reduce nirmatrelvir to 150 mg with ritonavir 100 mg every 12 hours. eGFR <30 mL/min: not recommended.</p></div>"
},
"code": {
"coding": [
{
"system": "http://www.whocc.no/atc",
"code": "J05AE30",
"display": "nirmatrelvir and ritonavir"
}
]
},
"status": "active",
"indicationGuideline": [
{
"indication": [
{
"concept": {
"text": "Treatment of mild-to-moderate COVID-19 in adults at high risk of progression to severe COVID-19"
}
}
],
"dosingGuideline": [
{
"treatmentIntent": {
"text": "Standard dose (normal to mild renal impairment)"
},
"dosage": [
{
"type": {
"text": "Nirmatrelvir"
},
"dosage": [
{
"text": "Nirmatrelvir 300 mg (two 150 mg tablets) orally every 12 hours for 5 days",
"timing": {
"repeat": {
"boundsDuration": {
"value": 5,
"unit": "day",
"system": "http://unitsofmeasure.org",
"code": "d"
},
"frequency": 1,
"period": 12,
"periodUnit": "h"
}
},
"route": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
},
"doseAndRate": [
{
"doseQuantity": {
"value": 300,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
}
}
]
}
]
},
{
"type": {
"text": "Ritonavir"
},
"dosage": [
{
"text": "Ritonavir 100 mg (one 100 mg tablet) orally every 12 hours for 5 days",
"timing": {
"repeat": {
"boundsDuration": {
"value": 5,
"unit": "day",
"system": "http://unitsofmeasure.org",
"code": "d"
},
"frequency": 1,
"period": 12,
"periodUnit": "h"
}
},
"route": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
},
"doseAndRate": [
{
"doseQuantity": {
"value": 100,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
}
}
]
}
]
}
],
"patientCharacteristic": [
{
"type": {
"coding": [
{
"system": "http://loinc.org",
"code": "62238-1",
"display": "Glomerular filtration rate/1.73 sq M.predicted"
}
]
},
"valueRange": {
"low": {
"value": 60,
"unit": "mL/min/1.73m2",
"system": "http://unitsofmeasure.org",
"code": "mL/min/{1.73_m2}"
}
}
}
]
},
{
"treatmentIntent": {
"text": "Reduced dose for moderate renal impairment (eGFR 30 to <60 mL/min)"
},
"dosage": [
{
"type": {
"text": "Nirmatrelvir"
},
"dosage": [
{
"text": "Nirmatrelvir 150 mg (one 150 mg tablet) orally every 12 hours for 5 days",
"timing": {
"repeat": {
"boundsDuration": {
"value": 5,
"unit": "day",
"system": "http://unitsofmeasure.org",
"code": "d"
},
"frequency": 1,
"period": 12,
"periodUnit": "h"
}
},
"route": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
},
"doseAndRate": [
{
"doseQuantity": {
"value": 150,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
}
}
]
}
]
},
{
"type": {
"text": "Ritonavir"
},
"dosage": [
{
"text": "Ritonavir 100 mg (one 100 mg tablet) orally every 12 hours for 5 days",
"timing": {
"repeat": {
"boundsDuration": {
"value": 5,
"unit": "day",
"system": "http://unitsofmeasure.org",
"code": "d"
},
"frequency": 1,
"period": 12,
"periodUnit": "h"
}
},
"route": {
"coding": [
{
"system": "https://standardterms.edqm.eu",
"code": "20053000",
"display": "Oral use"
}
]
},
"doseAndRate": [
{
"doseQuantity": {
"value": 100,
"unit": "mg",
"system": "http://unitsofmeasure.org",
"code": "mg"
}
}
]
}
]
}
],
"patientCharacteristic": [
{
"type": {
"coding": [
{
"system": "http://loinc.org",
"code": "62238-1",
"display": "Glomerular filtration rate/1.73 sq M.predicted"
}
]
},
"valueRange": {
"low": {
"value": 30,
"unit": "mL/min/1.73m2",
"system": "http://unitsofmeasure.org",
"code": "mL/min/{1.73_m2}"
},
"high": {
"value": 60,
"unit": "mL/min/1.73m2",
"system": "http://unitsofmeasure.org",
"code": "mL/min/{1.73_m2}"
}
}
}
]
},
{
"treatmentIntent": {
"text": "Severe renal impairment (eGFR <30 mL/min)"
},
"dosage": [
{
"type": {
"text": "PAXLOVID"
},
"dosage": [
{
"text": "PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min)"
}
]
}
],
"patientCharacteristic": [
{
"type": {
"coding": [
{
"system": "http://loinc.org",
"code": "62238-1",
"display": "Glomerular filtration rate/1.73 sq M.predicted"
}
]
},
"valueRange": {
"high": {
"value": 30,
"unit": "mL/min/1.73m2",
"system": "http://unitsofmeasure.org",
"code": "mL/min/{1.73_m2}"
}
}
}
]
}
]
}
]
}
}
]
}