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

 

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.

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)