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
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.
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^a	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	Potential for serious and/or life-threatening reactions.
Antipsychotics	pimozide	Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias.
Benign Prostatic Hyperplasia Agents	silodosin	Potential for postural hypotension.
Cardiovascular Agents	eplerenone ivabradine	Potential for hyperkalemia. Potential for bradycardia or conduction disturbances.
Ergot Derivatives	dihydroergotamine, ergonovine, ergotamine, methylergonovine^a	Potential for serious and/or life-threatening reactions, such as acute ergot toxicity 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	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.
Migraine Medications	ubrogepant	Potential for serious adverse reactions.
Mineralocorticoid Receptor Antagonists	finerenone	Potential for serious adverse reactions including hyperkalemia, hypotension, and hyponatremia.
Opioid Antagonists	naloxegol	Potential for opioid withdrawal symptoms.
PDE5 Inhibitors	sildenafil^b, 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.
PDE5 Inhibitors	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 midazolam^c, 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)