How to prescribe Paxlovid (nirmatrelvir/ritonavir) for a patient on atorvastatin (lipid-lowering medication) with COVID-19?

Managing Paxlovid in Patients on Atorvastatin

Temporarily hold atorvastatin during the 5-day Paxlovid treatment course, then resume it after completion of antiviral therapy. This approach eliminates the risk of statin-related toxicity from the significant drug-drug interaction while maintaining COVID-19 treatment efficacy.

Understanding the Drug Interaction

Ritonavir, a component of Paxlovid, is a potent CYP3A4 inhibitor that dramatically increases atorvastatin concentrations, creating substantial risk for myopathy and rhabdomyolysis. 1 The FDA prescribing information for Paxlovid includes a boxed warning specifically highlighting that ritonavir may lead to greater exposure of concomitant medications metabolized by CYP3A4, resulting in potentially severe or life-threatening events. 1

• Atorvastatin is highly dependent on CYP3A4 for metabolism, making it particularly vulnerable to this interaction. 2, 3
• Multiple case reports have documented increased toxicity risk when statins like atorvastatin are combined with Paxlovid. 2
• The interaction occurs rapidly due to ritonavir's potent and immediate inhibition of CYP3A4. 3

Recommended Management Strategy

The safest approach is to temporarily discontinue atorvastatin for the 5-day Paxlovid treatment course:

• Pause atorvastatin on day 1 of Paxlovid initiation. 3
• Resume atorvastatin after completing the full 5-day Paxlovid course. 3
• This brief interruption poses minimal cardiovascular risk, as statins have long-term benefits and short-term discontinuation (5 days) does not significantly impact cardiovascular outcomes. 3

Clinical Rationale

Pragmatic options for managing DDIs with Paxlovid are largely confined to preemptive pausing of comedications due to the short treatment window and difficulty implementing dose adjustments. 3

• The 5-day treatment course is too brief to safely implement atorvastatin dose reduction strategies. 3
• Clinical monitoring for myopathy symptoms during such a short period is unreliable and impractical. 3
• The benefit of Paxlovid in reducing hospitalization and death (39% relative risk reduction for hospitalization, 61% for death) strongly supports its use in eligible patients. 4

Important Prescribing Considerations

Before prescribing Paxlovid, review ALL patient medications to identify potential CYP3A4-dependent drugs:

• The FDA mandates reviewing all medications to assess drug-drug interactions before prescribing Paxlovid. 1
• Medications highly dependent on CYP3A4 for clearance may be contraindicated if elevated concentrations cause serious adverse events. 1
• Consider whether the patient is taking other statins, as management differs by agent (pravastatin and rosuvastatin have minimal CYP3A4 metabolism and may be safer alternatives if switching is feasible). 3

Common Pitfalls to Avoid

Do not attempt dose reduction of atorvastatin during Paxlovid treatment - the magnitude of CYP3A4 inhibition by ritonavir is too substantial and unpredictable to safely dose-adjust. 2, 3

Do not deny Paxlovid to high-risk patients solely due to atorvastatin use - the mortality and hospitalization benefits of Paxlovid outweigh the manageable risk from temporarily holding a statin. 1, 4

Do not forget to counsel patients to restart their atorvastatin after completing Paxlovid, as medication non-resumption is a common post-treatment issue. 3

Patient Eligibility Confirmation

Ensure the patient meets criteria for Paxlovid before addressing the drug interaction:

• Initiate treatment within 5 days of COVID-19 symptom onset. 1
• Confirm mild-to-moderate disease without supplemental oxygen requirement. 1
• Verify high-risk status for progression to severe COVID-19. 1
• Assess renal function and adjust Paxlovid dosing if eGFR is <60 mL/min. 1