What are the potential interactions between Paxlovid (nirmatrelvir/ritonavir) and medications such as aspirin, losartan, metoprolol, lansoprazole, and torsemide?

Drug Interactions Between Paxlovid and Common Medications

Paxlovid (nirmatrelvir/ritonavir) has significant drug interaction potential with aspirin, losartan, metoprolol, lansoprazole, and torsemide, requiring careful management and potential dose adjustments to prevent serious adverse effects.

Mechanism of Paxlovid Drug Interactions

Paxlovid's drug interaction potential stems primarily from the ritonavir component, which:

• Acts as a strong inhibitor of CYP3A4 enzymes
• Inhibits CYP2D6, P-glycoprotein (P-gp), and OATP1B1 transporters
• Can increase plasma concentrations of medications metabolized by these pathways 1

Specific Medication Interactions

Aspirin

• Interaction level: Low risk
• Mechanism: Minimal metabolism through affected pathways
• Management: No dose adjustment needed; can be safely continued during Paxlovid treatment

Losartan

• Interaction level: Moderate risk
• Mechanism: Losartan is metabolized by CYP3A4, leading to increased concentrations when co-administered with Paxlovid
• Management:
  • Monitor blood pressure closely
  • Consider reducing losartan dose by 50% during Paxlovid treatment
  • Watch for hypotension, dizziness, and electrolyte abnormalities 1

Metoprolol

• Interaction level: Moderate to high risk
• Mechanism: Metoprolol is primarily metabolized by CYP2D6, which is inhibited by ritonavir
• Management:
  • Monitor heart rate and blood pressure closely
  • Consider reducing metoprolol dose by 25-50%
  • Watch for bradycardia, hypotension, and heart block
  • Consider temporary switch to a beta-blocker with less CYP metabolism (e.g., atenolol) if clinically appropriate 1

Lansoprazole

• Interaction level: Moderate risk
• Mechanism: Lansoprazole is metabolized by CYP3A4 and CYP2C19
• Management:
  • Paxlovid's absorption is affected by gastric pH; take Paxlovid at least 4 hours before lansoprazole
  • Consider reducing lansoprazole dose by 50% during Paxlovid treatment
  • If possible, temporarily switch to famotidine (which has fewer interactions) 1

Torsemide

• Interaction level: Moderate risk
• Mechanism: Torsemide is partially metabolized by CYP2C9, with some CYP3A4 involvement
• Management:
  • Monitor fluid status, electrolytes, and renal function closely
  • Consider reducing torsemide dose by 25-50% if signs of increased diuretic effect occur
  • Watch for dehydration, electrolyte abnormalities, and hypotension 1

Risk Stratification and Management Approach

1. High-risk interactions (require alternative COVID-19 treatment or medication substitution):

   • Amiodarone, dronedarone, flecainide, propafenone, quinidine
   • Lovastatin, simvastatin, rosuvastatin
   • Sildenafil for pulmonary hypertension
   • Ergot derivatives, colchicine 2

2. Moderate-risk interactions (require dose adjustment and monitoring):

   • Losartan, metoprolol, lansoprazole, torsemide (as discussed above)
   • Calcium channel blockers (reduce dose by 50%)
   • Warfarin (monitor INR more frequently)
   • Tacrolimus and other immunosuppressants (significant dose reduction needed) 1, 3

3. Low-risk interactions (minimal or no adjustment needed):

   • Aspirin and most NSAIDs
   • Acetaminophen
   • Most antibiotics (except clarithromycin, erythromycin)

Clinical Monitoring Recommendations

• Cardiovascular monitoring: Check blood pressure and heart rate daily when taking Paxlovid with losartan or metoprolol
• Renal function: Monitor electrolytes and creatinine when using with torsemide
• Therapeutic drug monitoring: Consider for medications with narrow therapeutic windows
• Patient education: Inform about potential side effects and when to seek medical attention

Key Precautions

• The short 5-day course of Paxlovid limits the duration of interaction risk but doesn't eliminate it
• Elderly patients and those with renal or hepatic impairment are at higher risk of adverse effects from drug interactions
• Temporarily pausing interacting medications when possible is often safer than attempting complex dose adjustments
• Pharmacist consultation is strongly recommended before initiating Paxlovid in patients on multiple medications 1

Remember that these interactions can lead to serious adverse effects including hypotension, bradycardia, sedation, and organ toxicity if not properly managed. When in doubt, consider alternative COVID-19 treatments for patients on multiple interacting medications.