From the FDA Drug Label
PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance
There are certain other drugs for which concomitant use with PAXLOVID should be avoided and/or dose adjustment, interruption, or therapeutic monitoring is recommended.
Drugs listed in this section are a guide and not considered a comprehensive list of all drugs that may be contraindicated with PAXLOVID
The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor like PAXLOVID [see Drug Interactions (7. 3)]:
➢ Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7. 3)]:
• Alpha 1-adrenoreceptor antagonist: alfuzosin
• Antianginal: ranolazine
• Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
• Anti-gout: colchicine (in patients with renal and/or hepatic impairment [see Table 1, Drug Interactions (7. 3)])
• Antipsychotics: lurasidone, pimozide
• Benign prostatic hyperplasia agents: silodosin
• Cardiovascular agents: eplerenone, ivabradine
• Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
• HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 1, Drug Interactions (7. 3)])
• Immunosuppressants: voclosporin
• Microsomal triglyceride transfer protein inhibitor: lomitapide
• Migraine medications: eletriptan, ubrogepant
• Mineralocorticoid receptor antagonists: finerenone
• Opioid antagonists: naloxegol
• PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension (PAH)
• Sedative/hypnotics: triazolam, oral midazolam
• Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
• Vasopressin receptor antagonists: tolvaptan
➢ Drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.
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 Drug Interactions (7. 3)]:
• Anticancer drugs: apalutamide
• Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin
• Antimycobacterials: rifampin, rifapentine
• Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
• Herbal products: St. John's Wort (hypericum perforatum)
The medications that should not be taken with Paxlovid (nirmatrelvir/ritonavir) are:
- Alpha 1-adrenoreceptor antagonists: alfuzosin
- Anti-anginal: ranolazine
- Anti-arrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine
- Anti-gout: colchicine (in patients with renal and/or hepatic impairment)
- Antipsychotics: lurasidone, pimozide
- Benign prostatic hyperplasia agents: silodosin
- Cardiovascular agents: eplerenone, ivabradine
- Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
- HMG-CoA reductase inhibitors: lovastatin, simvastatin
- Immunosuppressants: voclosporin
- Microsomal triglyceride transfer protein inhibitor: lomitapide
- Migraine medications: eletriptan, ubrogepant
- Mineralocorticoid receptor antagonists: finerenone
- Opioid antagonists: naloxegol
- PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension (PAH)
- Sedative/hypnotics: triazolam, oral midazolam
- Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin
- Vasopressin receptor antagonists: tolvaptan
- Anticancer drugs: apalutamide
- Anticonvulsants: carbamazepine, phenobarbital, primidone, phenytoin
- Antimycobacterials: rifampin, rifapentine
- Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor
- Herbal products: St. John's Wort (hypericum perforatum) 1
From the Research
Paxlovid (nirmatrelvir/ritonavir) should not be taken with medications such as amiodarone, rivaroxaban, simvastatin, sildenafil (for pulmonary hypertension), St. John's wort, carbamazepine, phenobarbital, rifampin, colchicine (in renal/hepatic impairment), and ergot derivatives due to the risk of serious adverse effects. The primary concern with co-administering these medications with Paxlovid is the strong inhibition of the CYP3A4 enzyme by ritonavir, which can lead to increased blood levels of these medications and result in severe adverse effects, including cardiac arrhythmias, excessive bleeding, rhabdomyolysis, or respiratory depression 2. Some key points to consider when evaluating potential drug interactions with Paxlovid include:
- The medication's potential to interact with Paxlovid, with 56% of the 50 most commonly prescribed drugs showing no interaction, 30% having a potential for interaction, and 14% not being specifically mentioned in relation to Paxlovid 2
- The importance of careful consideration of potential drug interactions, especially in high-risk specialties such as diabetology, infectious diseases, internal medicine, and general medicine 2
- The need for a thorough assessment of concurrent medications to optimize safety and efficacy in patients receiving Paxlovid 2 Other serious interactions occur with medications like atorvastatin, rosuvastatin, certain antipsychotics (such as quetiapine and lurasidone), and immunosuppressants (tacrolimus, cyclosporine), which may require temporary discontinuation or dose adjustment during the 5-day Paxlovid course 3. It is essential for patients to provide a complete medication list, including over-the-counter drugs and supplements, before starting Paxlovid therapy to minimize the risk of adverse effects 3.