PAXLOVID 2 Contraindications

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Canada
 

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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
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.
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, quinidinea

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 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.

Cardiovascular Agents

eplerenone

ivabradine

Potential for hyperkalemia.

Potential for bradycardia or conduction disturbances.

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.
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.

Opioid Antagonists naloxegol

Potential for opioid withdrawal symptoms.

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)