Is it safe to give Paxlovid (nirmatrelvir/ritonavir) to a patient on rosuvastatin (Crestor) 40 mg daily?

Management of Rosuvastatin 40 mg with Paxlovid (Nirmatrelvir/Ritonavir)

It is not safe to administer Paxlovid to a patient on rosuvastatin 40 mg daily without dose adjustment; the rosuvastatin dose should be temporarily reduced to 10 mg daily during the 5-day Paxlovid treatment and for 2 days afterward.

Drug Interaction Mechanism

Ritonavir, a component of Paxlovid, is a potent inhibitor of:

• CYP3A4 enzymes
• P-glycoprotein (P-gp) transporters
• Breast cancer resistance protein (BCRP)
• Organic anion-transporting protein (OATP)

While rosuvastatin is minimally metabolized by CYP3A4, it is a substrate for OATP and BCRP transporters that are inhibited by ritonavir, leading to increased rosuvastatin exposure 1.

Evidence-Based Recommendations

Recent pharmacokinetic data shows:

• Rosuvastatin exposure (Cmax) increases approximately 2-fold when co-administered with ritonavir 1
• This is significantly less than the 4.76-fold increase seen with atorvastatin, but still clinically relevant 1

The risk is particularly concerning with:

• High-dose rosuvastatin (40 mg is the maximum approved dose)
• Short-term but potent inhibition from the 5-day Paxlovid course
• Increased risk of myopathy and rhabdomyolysis with elevated statin levels

Management Algorithm

1. Temporary dose reduction:

   • Reduce rosuvastatin from 40 mg to 10 mg daily during Paxlovid treatment 1
   • Maintain reduced dose during the 5-day Paxlovid course and for 2 days after completion

2. Monitoring:

   • Advise patient to report any muscle pain, tenderness, or weakness
   • Consider checking CPK levels if symptoms develop
   • Monitor for other statin adverse effects (headache, GI symptoms)

3. Resumption of regular dosing:

   • Return to regular rosuvastatin 40 mg dose 2 days after completing Paxlovid

4. Alternative approaches (if clinically indicated):

   • Consider temporarily switching to pravastatin or fluvastatin which have minimal interaction with ritonavir 2
   • For patients who absolutely cannot interrupt their high-intensity statin therapy, consider alternative COVID-19 treatments

Special Considerations

• Elderly patients (>65 years) are at higher risk of achieving excessive plasma concentrations of nirmatrelvir/ritonavir 3, potentially increasing the interaction risk
• Renal impairment may further increase both rosuvastatin and nirmatrelvir exposure, requiring additional caution 4
• Multiple medications increase complexity - 81.4% of patients on Paxlovid have drug-drug interactions 5

Common Pitfalls to Avoid

1. Complete statin discontinuation: Abrupt withdrawal may cause negative rebound effects on the cardiovascular system 2

2. Failure to adjust dose: Continuing full-dose rosuvastatin (40 mg) with Paxlovid increases risk of myopathy and rhabdomyolysis

3. Inadequate patient education: Patients must understand the temporary nature of the dose adjustment and when to resume normal dosing

4. Overlooking other interactions: Paxlovid interacts with numerous medications beyond statins, requiring comprehensive medication review

By temporarily reducing the rosuvastatin dose during Paxlovid treatment, you can minimize the risk of adverse effects while maintaining some lipid-lowering benefit during the short 5-day antiviral course.