Can patients taking statins (HMG-CoA reductase inhibitors) safely take Paxlovid (nirmatrelvir/ritonavir) for COVID-19?

Paxlovid and Statins: Managing Drug Interactions

Patients taking statins should temporarily discontinue or adjust their statin dosage when taking Paxlovid for COVID-19 due to significant drug-drug interactions that can lead to increased statin concentrations and potential toxicity. 1

Understanding the Interaction

Paxlovid (nirmatrelvir/ritonavir) contains ritonavir, which is a potent inhibitor of CYP3A4 enzymes. This creates significant drug-drug interactions with medications metabolized through this pathway, including most statins:

• Ritonavir in Paxlovid inhibits hepatic cytochrome P450 3A4, which metabolizes most statins 2
• This inhibition can lead to increased plasma concentrations of statins 3
• Even the short 5-day course of Paxlovid can significantly increase statin exposure 4

Specific Management Recommendations

Statin Management During Paxlovid Treatment

1. For lovastatin and simvastatin:

   • Temporarily discontinue during the 5-day Paxlovid treatment and for 3 days after
   • These are contraindicated with Paxlovid due to high risk of myopathy and rhabdomyolysis 1

2. For atorvastatin and rosuvastatin:

   • Reduce dose by 50% or temporarily discontinue during treatment
   • Resume regular dosing 3 days after completing Paxlovid 4

3. For pravastatin and fluvastatin:

   • These have minimal CYP3A4 metabolism and may be continued with caution
   • Monitor for muscle symptoms 4

4. For pitavastatin:

   • Minimal interaction expected; can generally be continued during Paxlovid treatment 5

Monitoring During Treatment

• Watch for symptoms of statin toxicity: muscle pain, tenderness, or weakness 3
• If severe symptoms develop, check creatine kinase levels and liver enzymes 3
• Resume normal statin dosing 3-5 days after completing the full Paxlovid course 5

Clinical Decision Algorithm

1. Identify statin type and risk:

   • High-risk statins (lovastatin, simvastatin): Discontinue
   • Moderate-risk statins (atorvastatin, rosuvastatin): Reduce dose or discontinue
   • Lower-risk statins (pravastatin, fluvastatin, pitavastatin): Continue with monitoring

2. Consider patient factors:

   • Recent cardiovascular event (within 3 months): Consult cardiology before interrupting
   • Stable cardiovascular disease: Brief statin interruption is generally safe
   • High cardiovascular risk but no recent event: Brief interruption acceptable

3. Implement management plan:

   • Communicate clear plan for statin interruption/reduction and resumption
   • Ensure patient understands signs of statin toxicity to report
   • Schedule follow-up after Paxlovid completion

Important Caveats and Pitfalls

• Don't continue high-risk statins: Continuing lovastatin or simvastatin with Paxlovid can lead to severe myopathy or rhabdomyolysis 1
• Don't forget to resume: Ensure patients resume their regular statin therapy after completing Paxlovid
• Don't ignore symptoms: Muscle pain, weakness, or dark urine during co-administration requires immediate evaluation
• Don't withhold Paxlovid: The benefit of Paxlovid in reducing hospitalization and death outweighs the temporary adjustment of statin therapy 5

The temporary management of statins during the short 5-day course of Paxlovid is a reasonable approach to minimize drug interaction risks while ensuring patients receive appropriate COVID-19 treatment.