Simvastatin and Lenacapavir: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lenacapavir
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Here's what's going on. Lenacapavir (Sunlenca or Yeztugo) is an HIV medicine that can slow down one of your body's main drug-clearing enzymes, called CYP3A. Simvastatin (Zocor) is a cholesterol medicine that this same enzyme breaks down. So when you take both, simvastatin can build up higher than usual in your body.
Too much simvastatin can raise the chance of muscle problems, like aches, weakness, or (rarely) more serious muscle damage. One thing to know is that lenacapavir stays in your body a long time, so this can matter for months even after your last dose. The good news is your care team can manage this easily by using a low simvastatin dose and keeping an eye on you.
Effect: Increased simvastatin exposure via lenacapavir-mediated inhibition of CYP3A. Lenacapavir is a moderate CYP3A inhibitor; simvastatin is a sensitive CYP3A substrate, so higher simvastatin AUC/Cmax is expected, increasing myopathy/rhabdomyolysis risk.
- Direction: Increased statin effect and toxicity risk (neither drug is a prodrug here).
- Onset: Unspecified; relevant for statins started within ~9 months of the last lenacapavir dose given its long half-life.
- Evidence: Theoretical.
- Management: Initiate simvastatin at the lowest dose, titrate cautiously, monitor for muscle symptoms and consider CK if symptomatic.
What happens
Increased simvastatin exposure
Interaction Deep Dive
When lenacapavir (a moderate inhibitor of CYP3A) is given alongside simvastatin (a sensitive substrate of CYP3A), simvastatin exposure can rise. For medications metabolized chiefly by CYP3A that are started within 9 months following the final lenacapavir dose, lenacapavir may raise their exposure, thereby potentially heightening the risk of adverse reactions as well12. Begin simvastatin at its lowest possible starting dose and increase it cautiously, keeping watch for safety concerns such as myopathy1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of simvastatin
How to manage this interaction
This is manageable with the right dosing and monitoring. Keep taking both medicines as prescribed and don't stop either one on your own.
- Your care team will likely start simvastatin at the lowest dose and adjust it slowly and individually for you.
- They may monitor you more closely for muscle side effects, since lenacapavir can affect statin levels for months after your last dose.
- Tell your pharmacist or doctor right away if you notice unexplained muscle pain, tenderness, weakness, or dark-colored urine.
- Ask your pharmacist to review your full medication list, especially if simvastatin is new.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Simvastatin and Lenacapavir together?
Lenacapavir can raise simvastatin levels and increase the risk of muscle side effects, so simvastatin should be started low and titrated carefully. Keep taking both as prescribed and report any muscle pain or weakness to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Lenacapavir interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Simvastatin and Lenacapavir interaction managed?
This is manageable with the right dosing and monitoring. Keep taking both medicines as prescribed and don't stop either one on your own. Your care team will likely start simvastatin at the lowest dose and adjust it slowly and individually for you. They may monitor you more closely for muscle side effects, since lenacapavir can affect statin levels for months after your last dose. Tell your pharmac… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Simvastatin or Lenacapavir need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: SUNLENCA(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per FDA), Foster City, CA, 2024. DailyMed
- Product Information: YEZTUGO(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2025. DailyMed
Keep reading about Lenacapavir
Keep reading about Simvastatin
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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