Amprenavir and Simvastatin: 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
Amprenavir
No brand names on recordSimvastatin
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.
These two medicines should not be taken together. Amprenavir is an HIV medicine, and simvastatin (Zocor, Flolipid) lowers cholesterol. Your body normally uses a liver enzyme called CYP3A4 to break simvastatin down. Amprenavir slows that enzyme, so simvastatin can build up to much higher levels than intended.
When simvastatin gets too high, it can cause serious muscle problems, including muscle pain, weakness, and a rare but dangerous breakdown of muscle called rhabdomyolysis. The good news is your care team can easily manage this by choosing a safer cholesterol option. Please don't stop either drug on your own, but do talk with your pharmacist or doctor soon.
Contraindicated combination. Simvastatin is a CYP3A4 substrate; amprenavir is a CYP3A4 inhibitor. Inhibition of simvastatin's presystemic and hepatic metabolism is expected to raise simvastatin (and active acid metabolite) plasma exposure, increasing the risk of dose-dependent myopathy and rhabdomyolysis.
- Direction: increased simvastatin effect/toxicity
- Evidence: theoretical (mechanism-based), but severity graded contraindicated
- Onset: unspecified
- Management: avoid coadministration. Select a statin not dependent on CYP3A4 (e.g., pravastatin, rosuvastatin) per lipid goals, or an alternate lipid-lowering strategy. Counsel on muscle pain, weakness, and dark urine.
What happens
An increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Taking simvastatin together with a protease inhibitor like amprenavir is contraindicated because it may raise the likelihood of myopathy and rhabdomyolysis. Because simvastatin is metabolized as a CYP3A4 substrate1 and amprenavir acts to inhibit CYP3A4, using the two agents together can elevate the plasma concentrations of simvastatin2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated simvastatin metabolism by amprenavir
How to manage this interaction
This pairing is best avoided, and your care team can handle that. Because amprenavir raises simvastatin levels, the usual approach is to switch rather than adjust the dose.
- Keep taking your HIV medicine as prescribed; your prescriber will typically choose a different cholesterol medicine that isn't affected the same way.
- Ask your pharmacist or doctor before starting or refilling either drug together.
- Watch for unexplained muscle pain, tenderness, weakness, or dark-colored urine, and report these promptly.
Don't stop anything on your own; let your care team make the switch safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amprenavir and Simvastatin together?
Amprenavir and simvastatin should not be used together because amprenavir can raise simvastatin levels and cause serious muscle damage; your doctor will likely switch you to a safer cholesterol medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amprenavir and Simvastatin interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amprenavir and Simvastatin interaction managed?
This pairing is best avoided, and your care team can handle that. Because amprenavir raises simvastatin levels, the usual approach is to switch rather than adjust the dose. Keep taking your HIV medicine as prescribed; your prescriber will typically choose a different cholesterol medicine that isn't affected the same way. Ask your pharmacist or doctor before starting or refilling either drug togeth… 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 Amprenavir or Simvastatin 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: ZOCOR(R) oral tablets, simvastatin oral tablets. Merck Sharp & Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2011. DailyMed
- Product Information: AGENERASE(R) oral solution, amprenavir oral solution. GlaxoSmithKline (per DailyMed), Research Triangle Park, NC, 2005.
Keep reading about Amprenavir
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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