Is it safe to use rosuvastatin and Paxlovid (nirmatrelvir and ritonavir) together?

Rosuvastatin and Paxlovid Drug Interaction

Rosuvastatin must be temporarily discontinued during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) due to the risk of severe statin toxicity, including rhabdomyolysis. 1

Why This Combination Is Contraindicated

The FDA explicitly lists simvastatin and lovastatin as contraindicated with Paxlovid, and rosuvastatin carries similar risks due to ritonavir's potent inhibition of drug transporters. 1

• Ritonavir, the pharmacokinetic enhancer in Paxlovid, is a strong CYP3A4 inhibitor that dramatically increases plasma concentrations of statins metabolized through this pathway 1, 2
• While rosuvastatin is not primarily metabolized by CYP3A4, it is a substrate of OATP1B1 and BCRP transporters, which are inhibited by ritonavir 3, 4
• Studies with similar ritonavir-boosted regimens (hepatitis C antivirals) demonstrated a 19-fold increase in rosuvastatin exposure when combined with OATP1B1/BCRP inhibitors 3
• This massive increase in rosuvastatin levels creates unacceptable risk for myopathy, rhabdomyolysis, and acute kidney injury 4, 5

Clinical Management Strategy

Temporarily stop rosuvastatin for the 5-day Paxlovid treatment course, then resume at the previous dose after completion. 5, 2

During Paxlovid Treatment (Days 1-5):

• Hold rosuvastatin completely — do not attempt dose reduction, as even low doses may reach toxic levels 5, 2
• The 5-day interruption poses minimal cardiovascular risk, as abrupt statin withdrawal effects typically require longer discontinuation periods 5
• Counsel patients that temporary statin interruption is safer than risking severe muscle toxicity 2, 6

After Paxlovid Completion:

• Resume rosuvastatin at the original dose on Day 6 (24 hours after the last Paxlovid dose) 5
• Ritonavir's inhibitory effects on transporters resolve within 24-48 hours after discontinuation 2, 6
• Monitor for muscle symptoms (pain, weakness, dark urine) for 2 weeks after resuming, though risk is low with proper timing 4, 7

Alternative Statin Options (If Continuous Therapy Required)

If a patient absolutely requires continuous lipid-lowering during Paxlovid treatment, pravastatin or fluvastatin are the only acceptable alternatives, as they are not metabolized by CYP3A4 and have minimal transporter interactions. 3, 5

• Pravastatin is metabolized by glucuronidation and can be continued at standard doses during Paxlovid therapy 3, 5
• Fluvastatin is metabolized by CYP2C9 (not CYP3A4) and is also safe to continue 5
• Atorvastatin requires significant dose reduction (to 10-20 mg maximum) if continuation is necessary, but carries higher risk than pravastatin/fluvastatin 3, 5
• Simvastatin and lovastatin are absolutely contraindicated and must be switched before starting Paxlovid 1

Critical Pitfalls to Avoid

• Do not reduce rosuvastatin dose and continue — even 5 mg daily may reach toxic levels with ritonavir's 19-fold increase in exposure 3
• Do not restart rosuvastatin before completing the full 5-day Paxlovid course — overlapping therapy creates the interaction risk 2, 6
• Do not assume all statins behave identically — pravastatin and fluvastatin are safe, while simvastatin/lovastatin are contraindicated 3, 1, 5
• Do not forget to check all other medications — Paxlovid interacts with numerous cardiovascular drugs beyond statins, including anticoagulants, calcium channel blockers, and antiarrhythmics 1, 2, 6

Patient Counseling Points

• Explain that stopping rosuvastatin for 5 days will not increase cardiovascular risk 5
• Warn about signs of muscle toxicity if they accidentally continue the statin: severe muscle pain, weakness, dark/cola-colored urine, fever 4, 7
• Emphasize the importance of completing the full 5-day Paxlovid course for COVID-19 treatment effectiveness 1, 8
• Provide clear written instructions on when to stop and restart rosuvastatin to prevent confusion 1