Does a patient need to stop taking rosuvastatin (statin) while on Paxlovid (nirmatrelvir/ritonavir)?

Management of Rosuvastatin During Paxlovid Treatment

Rosuvastatin should be temporarily discontinued during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) therapy due to significant drug interaction risk.

Mechanism of Interaction

Ritonavir, a component of Paxlovid, is a potent inhibitor of CYP3A4 and transporters including:

• P-glycoprotein (P-gp)
• Breast cancer resistance protein (BCRP)
• Organic anion-transporting polypeptide (OATP1B1 and OATP1B3)

Rosuvastatin is primarily a substrate of BCRP and OATP transporters. When co-administered with ritonavir:

• Plasma concentrations of rosuvastatin can increase up to 19-fold 1
• This dramatic increase significantly elevates the risk of statin-associated myopathy

Risk Assessment

The increased rosuvastatin exposure during Paxlovid treatment can lead to:

• Myalgia (muscle pain)
• Myopathy (muscle weakness)
• Potential rhabdomyolysis (severe muscle breakdown)
• Elevated creatine kinase (CK) levels
• Potential kidney damage

Management Algorithm

1. Before starting Paxlovid:

   • Temporarily discontinue rosuvastatin for the 5-day course of Paxlovid
   • No tapering is required; statins can be safely interrupted for short periods

2. During Paxlovid treatment:

   • Monitor for any muscle symptoms (pain, weakness, tenderness)
   • If urgent lipid management is needed, consider non-statin alternatives

3. After completing Paxlovid:

   • Resume rosuvastatin at the same dose 1-2 days after completing the 5-day Paxlovid course
   • No dose adjustment is typically needed when restarting

4. Special considerations:

   • For high-risk patients (elderly, renal impairment, multiple medications), consider checking CK levels before restarting rosuvastatin 2
   • If the patient experiences muscle symptoms after restarting, evaluate for potential myopathy

Clinical Rationale

The temporary discontinuation of rosuvastatin during the short 5-day course of Paxlovid:

• Prevents potentially serious adverse effects from elevated statin levels
• Has minimal impact on long-term lipid management and cardiovascular risk
• Aligns with the principle of prioritizing immediate patient safety

Common Pitfalls to Avoid

1. Attempting dose reduction instead of discontinuation:

   • Even at reduced doses, the interaction can still lead to dangerously high rosuvastatin levels

2. Substituting with another statin:

   • Most statins interact with ritonavir; atorvastatin, simvastatin, and lovastatin have even more severe interactions

3. Continuing rosuvastatin with increased monitoring:

   • The magnitude of interaction (up to 19-fold increase) makes this approach unsafe

4. Extending Paxlovid treatment duration:

   • Standard 5-day course should not be extended to accommodate statin management

Evidence Quality Assessment

The recommendation to discontinue rosuvastatin during Paxlovid treatment is based on:

• Direct evidence of significant drug interactions via established pharmacokinetic mechanisms
• Consistent guidance across hepatology and cardiology guidelines
• Clear contraindication in drug labeling information

The short-term discontinuation of statin therapy for 5 days poses minimal cardiovascular risk compared to the potential serious adverse effects of the drug interaction.