Is Paxlovid (nirmatrelvir/ritonavir) safe to take with amlodipine (calcium channel blocker)?

Paxlovid and Amlodipine Interaction: Management Recommendations

Paxlovid (nirmatrelvir/ritonavir) can be taken with amlodipine, but caution is warranted and clinical monitoring is recommended as ritonavir may increase amlodipine levels, potentially requiring a dose reduction of amlodipine during the 5-day Paxlovid treatment course.

Understanding the Interaction

The interaction between Paxlovid and amlodipine occurs primarily due to the ritonavir component of Paxlovid:

• Ritonavir is a strong CYP3A4 inhibitor that can increase plasma concentrations of drugs metabolized by this enzyme 1
• Amlodipine is a substrate of CYP3A4, making it susceptible to this interaction 2
• The FDA label for Paxlovid specifically mentions this interaction, stating: "Caution is warranted and clinical monitoring of patients is recommended. A dose decrease may be needed for these drugs when co-administered with PAXLOVID" 1

Clinical Management Approach

During 5-day Paxlovid Treatment:

1. Continue amlodipine but monitor closely

   • Monitor blood pressure daily during Paxlovid treatment
   • Watch for signs of calcium channel blocker toxicity:
     • Excessive hypotension
     • Peripheral edema
     • Headache
     • Flushing

2. Consider amlodipine dose adjustment

   • If patient develops significant hypotension or other side effects:
     • Consider temporarily reducing amlodipine dose by 50% during the 5-day Paxlovid course
     • Return to regular dosing after completing Paxlovid

3. Special considerations

   • For elderly patients or those with hepatic impairment: Consider preemptive dose reduction
   • For patients on high-dose amlodipine (10mg): Monitor more frequently

Safety Profile of Amlodipine

Amlodipine is generally safer than non-dihydropyridine calcium channel blockers when used with Paxlovid:

• Unlike diltiazem and verapamil (which are contraindicated in heart failure), amlodipine has been shown to be safe in patients with severe heart failure in the PRAISE trial 2
• Amlodipine has predominant peripheral vasodilatory effects with minimal direct effects on cardiac conduction 3
• The European Society of Cardiology guidelines specifically note that amlodipine "appeared to be safe in patients with severe systolic HF" 2

Important Warnings

• Do not substitute with other calcium channel blockers: Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) have stronger interactions with Paxlovid and should be avoided if possible 2
• Watch for peripheral edema: This is the most common side effect of amlodipine that may worsen with increased plasma levels 3
• Avoid other CYP3A4 inhibitors: During Paxlovid treatment, avoid adding other medications that inhibit CYP3A4 as this could further increase amlodipine levels 1
• Particular caution in patients with severe renal impairment: The Paxlovid dose should be adjusted in these patients, but the interaction with amlodipine remains a concern 1

Conclusion

The combination of Paxlovid and amlodipine can be used together with appropriate monitoring and potential dose adjustment of amlodipine. The short 5-day course of Paxlovid limits the duration of the interaction, making it manageable in most clinical scenarios.