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):
Drug Class |
Drugs Within Class that are Contraindicated with PAXLOVID |
Clinical Comment |
|
---|---|---|---|
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, quinidine |
Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. |
|
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. |
|
neratinib |
Potential for serious and/or life-threatening reactions including hepatotoxicity. |
||
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. |
||
Anticoagulant |
rivaroxaban |
Potential of increased rivaroxaban plasma concentrations which may lead to risk of increased bleeding. |
|
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). |
|
Anti-gout |
colchicine |
Potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see Table 4). |
|
Antihistamines |
astemizolea, terfenadinea |
Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. |
|
Antimycobacterial |
rifampin |
Decreased plasma concentration and reduced clinical effects of nirmatrelvir and ritonavir. |
|
Antipsychotics |
lurasidone
pimozide |
Potential for serious and/or life-threatening reactions. Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. |
|
Ergot Derivatives |
dihydroergotamine, ergonovine, ergotaminea, |
Potential for serious and/or life-threatening reactions, such as acute ergot toxicity |
|
methylergonovinea |
characterized by vasospasm and tissue ischemia. |
||
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
Microsomal Triglyceride Transfer Protein (MTTP) Inhibitor |
lovastatin, simvastatin
lomitapide |
Potential for serious reactions, such as risk of myopathy including rhabdomyolysis.
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. |
|
PDE5 Inhibitors |
sildenafilb, only when used for the treatment of pulmonary arterial hypertension (PAH)
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.
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. |
|
|
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, phenytoin
- Antimycobacterial: rifampin
- Herbal products: St. John’s Wort (hypericum perforatum)