Nirmatrelvir/Ritonavir and Simvastatin Interaction
Drug interaction information between Nirmatrelvir/Ritonavir and Simvastatin.
Nirmatrelvir/Ritonavir and Simvastatin have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Nirmatrelvir/Ritonavir and Simvastatin. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
This medicine stops your body from breaking down simvastatin, which can lead to high levels that cause serious muscle damage.
What To Do
Stop taking simvastatin at least 12 hours before starting Paxlovid and do not start it again until 5 days after you finish the treatment.
FDA Label Information
HMG-CoA reductase inhibitors lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Co-administration contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ] . If treatment with PAXLOVID is considered medically necessary, discontinue use of lovastatin and simvastatin at least 12 hours prior to initiation of PAXLOVID, during the 5 days of PAXLOVID treatment, and for 5 days after completing PAXLOVID.
Nirmatrelvir/Ritonavir Also Interacts With
- Lovastatin major
- Sildenafil major
- Carbamazepine major
- Rifampin major
- Lurasidone major
Simvastatin Also Interacts With
- Diltiazem major
- Verapamil major
- Cyclosporine major
- Amiodarone major
- Dronedarone major
Frequently Asked Questions
Can I take Nirmatrelvir/Ritonavir and Simvastatin together?
This is a major interaction. Stop taking simvastatin at least 12 hours before starting Paxlovid and do not start it again until 5 days after you finish the treatment.
How serious is the interaction between Nirmatrelvir/Ritonavir and Simvastatin?
This interaction is classified as "major" severity by the FDA. Major interactions may be life-threatening or cause serious side effects.
Why do Nirmatrelvir/Ritonavir and Simvastatin interact?
This medicine stops your body from breaking down simvastatin, which can lead to high levels that cause serious muscle damage.
Understanding the Nirmatrelvir/Ritonavir and Simvastatin Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Nirmatrelvir/Ritonavir belongs to the Antiviral (Protease Inhibitor Combination) class and Simvastatin belongs to the HMG-CoA Reductase Inhibitor (Statin) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: This medicine stops your body from breaking down simvastatin, which can lead to high levels that cause serious muscle damage. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Nirmatrelvir/Ritonavir has 86 total documented interactions on file in this dataset, and Simvastatin has 41. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Stop taking simvastatin at least 12 hours before starting Paxlovid and do not start it again until 5 days after you finish the treatment. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Nirmatrelvir/Ritonavir or Simvastatin based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.