PAXLOVID 2 Contraindications | Pfizer Medical Information

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):

**Table 1:** **Drugs that are contraindicated for concomitant use with PAXLOVID**
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, bepridil^a, 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.
	venetoclax^d		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	astemizole^a, terfenadine^a	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, ergotamine^a,	Potential for serious and/or life-threatening reactions, such as acute ergot toxicity
Ergot Derivatives	methylergonovine^a	characterized by vasospasm and tissue ischemia.
GI Motility Agent	cisapride^a	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	sildenafil^b, 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 midazolam^c, triazolam	Potential for serious and/or life-threatening reactions, such as prolonged or increased sedation or respiratory depression.
a. Product no longer marketed in Canada. b. See 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS for co-administration of sildenafil in patients with erectile dysfunction. c. See Table 4 for parenterally administered midazolam. Oral formulation of midazolam is not marketed in Canada. d. See Table 4 for coadministration of the maintenance dose of venetoclax.

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)