PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
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.
PAXLOVID is also contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir/ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance (see Table 1 and 9 DRUG INTERACTIONS):
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Drug Class | Drugs Within Class that are Contraindicated with PAXLOVID | Clinical Comment | |
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Alpha1-Adrenoreceptor Antagonist | alfuzosin | Potential for serious reactions, such as hypotension (see Table 4). | |
Antianginal |
ranolazine |
Potential for serious and/or life-threatening reactions. | |
Antiarrhythmics |
amiodarone, bepridila, dronedarone, flecainide, propafenone, quinidinea |
Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. |
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Antibiotic |
fusidic acid | Potential of increased fusidic acid-associated adverse events, such as hepatitis or bone marrow suppression. | |
Anticancer |
apalutamide |
Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of PAXLOVID and potential loss of virologic response. In addition, exposure of apalutamide may increase with co-administration of PAXLOVID that may lead to serious adverse events including seizure and fracture. |
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neratinib |
Potential for serious and/or life-threatening reactions including hepatotoxicity. |
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venetoclaxd |
Concomitant use of strong CYP3A inhibitors, such as PAXLOVID, and venetoclax may increase the risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase. |
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Anticoagulant | rivaroxaban |
Potential of increased rivaroxaban plasma concentrations which may lead to risk of increased bleeding. |
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Anticonvulsants |
carbamazepine, phenobarbital, phenytoin |
Decreased plasma concentration and reduced clinical effects of nirmatrelvir and ritonavir. | |
Antifungal | voriconazole |
Significant reduction in voriconazole plasma concentrations and possible loss of effect (see Table 4). |
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Anti-gout | colchicine | Potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see Table 4). | |
Antihistamines |
astemizolea, |
Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. |
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Antimycobacterial | rifampin |
Decreased plasma concentration and reduced clinical effects of nirmatrelvir and ritonavir. |
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Antipsychotics | lurasidone | Potential for serious and/or life-threatening reactions. | |
pimozide | Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. | ||
Benign Prostatic Hyperplasia Agents | silodosin |
Potential for postural hypotension. |
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Cardiovascular Agents |
eplerenone ivabradine |
Potential for hyperkalemia. Potential for bradycardia or conduction disturbances. |
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Ergot Derivatives | dihydroergotamine, ergonovine, ergotamine, methylergonovinea | Potential for serious and/or life-threatening reactions, such as acute ergot toxicity characterized by vasospasm and tissue ischemia. |
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GI Motility Agent | cisapridea | Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. | |
Herbal Products | St. John’s wort (Hypericum perforatum) | May lead to loss of virologic response and possible resistance to PAXLOVID or to the class of protease inhibitors. | |
Lipid-modifying Agents | |||
HMG-CoA Reductase Inhibitors |
lovastatin, simvastatin |
Potential for serious reactions, such as risk of myopathy including rhabdomyolysis. | |
Microsomal Triglyceride Transfer Protein (MTTP) Inhibitor | lomitapide | Potential for serious reactions, such as hepatotoxicity. | |
Long-Acting Beta- Adrenoceptor | salmeterol | May result in potential increased risk of cardiovascular adverse events associated with salmeterol. | |
Migraine Medications | eletriptan | 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. | |
ubrogepant | Potential for serious adverse reactions. | ||
Mineralocorticoid Receptor Antagonists |
finerenone |
Potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia. |
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Opioid Antagonists | naloxegol |
Potential for opioid withdrawal symptoms. |
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PDE5 Inhibitors |
sildenafilb, only when used for the treatment of pulmonary arterial hypertension (PAH) |
Potential increase in PDE5 inhibitor associated adverse reactions including hypotension, syncope, visual changes, and prolonged erection. | |
vardenafil, when used for the treatment of erectile dysfunction or PAH | Potential increase in PDE5 inhibitor associated adverse reactions including hypotension, syncope, visual changes, and prolonged erection. | ||
Sedative/Hypnotics | orally administered midazolamc, triazolam | Potential for serious and/or life-threatening reactions, such as prolonged or increased sedation or respiratory depression. | |
Serotonin Receptor 1A Agonist/Serotonin Receptor 2A Antagonist |
flibanserin | Potential for hypotension, syncope, and CNS depression. | |
Vasopressin Receptor Antagonists | tolvaptan | Potential for dehydration, hypovolemia and hyperkalemia. |
PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer (see 9 DRUG INTERACTIONS):
- Anticancer agents: apalutamide
- Anticonvulsants: carbamazepine, phenobarbital, primidone, phenytoin
- Antimycobacterial: rifampin
- Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
- Herbal products: St. John’s Wort (hypericum perforatum)