What medications interact with Paxlovid (nirmatrelvir/ritonavir)?

Medications That Interact with Paxlovid (Nirmatrelvir/Ritonavir)

Paxlovid has numerous significant drug interactions due to ritonavir's strong inhibition of CYP3A4 enzymes and effects on other metabolic pathways, requiring careful medication review before prescribing to avoid potentially life-threatening interactions. 1

Mechanism of Drug Interactions

Paxlovid causes drug interactions through several mechanisms:

• Strong inhibition of CYP3A enzymes (primary mechanism)
• Inhibition of CYP2D6
• Inhibition of P-glycoprotein (P-gp) transporters
• Inhibition of OATP1B1 transporters 1

These interactions can significantly increase plasma concentrations of co-administered medications, potentially leading to serious adverse effects.

Contraindicated Medications (Do Not Co-administer)

The following medications are absolutely contraindicated with Paxlovid:

• Alpha-1 adrenoreceptor antagonists: Alfuzosin (risk of hypotension)
• Antianginals: Ranolazine (risk of serious/life-threatening reactions)
• Antiarrhythmics: Amiodarone, dronedarone, flecainide, propafenone, quinidine (risk of cardiac arrhythmias)
• Anticancer drugs: Apalutamide, enzalutamide (reduce Paxlovid effectiveness)
• Anticonvulsants: Carbamazepine, phenobarbital, phenytoin (reduce Paxlovid effectiveness)
• Antimycobacterials: Rifampin, rifabutin, rifapentine (reduce Paxlovid effectiveness)
• Herbal products: St. John's wort (reduces Paxlovid effectiveness)
• Statins: Lovastatin, simvastatin (risk of myopathy including rhabdomyolysis) 1

Medications Requiring Dose Adjustment or Temporary Discontinuation

Anticoagulants

• Rivaroxaban: Avoid concomitant use (increased bleeding risk)
• Apixaban: Dose reduction required (refer to apixaban label)
• Dabigatran: Dose reduction may be needed based on indication and renal function
• Warfarin: Close INR monitoring required 1

Statins

• Atorvastatin: Reduce dose or temporarily discontinue
• Rosuvastatin: Reduce dose (not recommended at high doses) 2

Immunosuppressants

• Tacrolimus: Requires significant dose reduction and therapeutic drug monitoring
• Cyclosporine: Requires dose reduction and monitoring 3

Antipsychotics

• Quetiapine: Reduce dose or temporarily discontinue
• Clozapine: Requires careful monitoring 3

Calcium Channel Blockers

• Amlodipine, diltiazem, felodipine, nifedipine, verapamil: Require dose reduction 3

Monitoring Recommendations

1. Before prescribing Paxlovid:

   • Complete medication reconciliation including all prescription, OTC, and herbal products
   • Identify potential interactions using drug interaction databases
   • Determine if medications can be safely paused, dose-adjusted, or require alternative COVID-19 treatment

2. During Paxlovid treatment:

   • Monitor for signs of toxicity from increased drug levels
   • For medications that cannot be paused but require dose adjustment, implement appropriate monitoring
   • Be particularly vigilant with narrow therapeutic index drugs

3. After completing Paxlovid:

   • Resume normal medication dosing 2-3 days after completing Paxlovid course
   • Ritonavir's enzyme inhibition effects may persist for 3-5 days 4

Common Pitfalls to Avoid

1. Failing to recognize "hidden" ritonavir: Remember that Paxlovid contains ritonavir, which has extensive drug interaction potential even at the low doses used

2. Overlooking non-prescription medications: Many OTC medications and supplements can interact with Paxlovid

3. Assuming a 5-day course is "too short" to cause problems: Even short-term Paxlovid can cause significant interactions

4. Not considering alternatives: For patients on multiple interacting medications, alternative COVID-19 treatments may be safer

5. Inadequate monitoring: Some interactions may require laboratory monitoring or close clinical follow-up during and after treatment 5

Algorithm for Managing Paxlovid Drug Interactions

1. Identify all patient medications (prescription, OTC, supplements)
2. Check each medication against Paxlovid interaction database
3. Categorize interactions:
   • Contraindicated (do not use Paxlovid)
   • Requires dose adjustment (implement specific adjustments)
   • Requires temporary discontinuation (hold medication)
   • No significant interaction (can continue as prescribed)
4. If contraindicated medications cannot be paused, consider alternative COVID-19 treatments
5. Document all medication changes and provide clear instructions to the patient

Remember that this is not a comprehensive list of all possible interactions. Always consult current drug interaction databases and product labeling for the most up-to-date information when prescribing Paxlovid.