Simvastatin and Atazanavir: 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
Atazanavir
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.
These two medicines should not be taken together. Atazanavir (Reyataz) is an HIV medicine that slows down a liver enzyme (called CYP3A) that normally breaks down simvastatin (Zocor). When that enzyme is blocked, simvastatin builds up in your blood to much higher levels than intended.
Too much simvastatin can cause serious muscle problems. You might notice muscle pain, tenderness, or weakness. In rare cases this can become a dangerous condition called rhabdomyolysis, where muscle breaks down and harms the kidneys. The good news: your care team can manage this easily by choosing a different cholesterol medicine that is safer with atazanavir. Please talk with your pharmacist or doctor before changing anything.
Contraindicated combination. Atazanavir is a potent CYP3A inhibitor; simvastatin is a CYP3A substrate (active statin, not a prodrug in the relevant sense here). Coadministration markedly increases simvastatin plasma exposure (AUC/Cmax), raising the risk of dose-dependent myopathy and rhabdomyolysis.
- Direction: increased simvastatin effect/toxicity
- Onset: delayed
- Evidence: probable
- Management: avoid the combination. Select an alternative agent per product labeling (e.g., a statin not primarily metabolized by CYP3A, or a non-statin), individualized by the care team. If muscle symptoms occur, evaluate CK and renal function.
What happens
An increased risk of simvastatin toxicity, including an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
The combined administration of atazanavir with simvastatin is contraindicated. Because atazanavir inhibits CYP3A and simvastatin is a substrate of CYP3A, giving the two together can raise simvastatin plasma levels, which may lead to myopathy, including rhabdomyolysis12.
Why it happens (mechanism)
Inhibition of CYP3A-mediated simvastatin metabolism by atazanavir
How to manage this interaction
The main step here is choosing a different medicine, not adjusting a dose. Because atazanavir strongly raises simvastatin levels, these two are not used together.
- Do not stop either medicine on your own. Keep taking what you were prescribed until you speak with your prescriber or pharmacist.
- Ask your care team whether a different cholesterol medicine that is safer with atazanavir would be right for you.
- Report any muscle pain, tenderness, weakness, or dark-colored urine right away.
Your care team can safely manage this by tailoring your cholesterol treatment to your HIV therapy.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A 72-year-old man developed rhabdomyolysis and acute renal failure while taking simvastatin together with amiodarone. He came in reporting 4 days of widespread pain, weakness, and fatigue, along with 3 days of dark orange urine. He had taken atorvastatin 40 mg daily for 2 years and was changed to simvastatin 80 mg 27 days before this presentation. In addition, amiodarone 400 mg daily was started 19 days before this presentation and then reduced to 200 mg daily after 7 days. His other long-term medications were atazanavir, stavudine, and delavirdine, each taken for 2 years. Laboratory testing showed a creatine kinase level of 66,680 units/liter, close to 300 times the upper limit of normal. He was diagnosed with rhabdomyolysis and oliguric acute renal failure. Simvastatin, amiodarone, and the HIV medications were all temporarily stopped, and the patient received forced alkaline diuresis and dialysis. He was discharged on day 9 (creatine kinase level, 1695 units/liter), had amiodarone restarted, and continued outpatient dialysis for one month. His HIV medications were resumed after 6 weeks, but the statin was not restarted. This patient had additional risk factors of advanced age and concurrent atazanavir use, in which atazanavir may have played a role by further reducing simvastatin's metabolism. The Naranjo adverse drug event probability scale gave a "probable" rating that the effects resulted from an interaction between simvastatin and amiodarone/atazanavir 3.
Common questions
Can I take Simvastatin and Atazanavir together?
Atazanavir and simvastatin should not be taken together because atazanavir causes simvastatin to build up, raising the risk of serious muscle damage. Talk to your doctor or pharmacist about a safer cholesterol medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Atazanavir interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Simvastatin and Atazanavir interaction managed?
The main step here is choosing a different medicine, not adjusting a dose. Because atazanavir strongly raises simvastatin levels, these two are not used together. Do not stop either medicine on your own. Keep taking what you were prescribed until you speak with your prescriber or pharmacist. Ask your care team whether a different cholesterol medicine that is safer with atazanavir would be right fo… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
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 Atazanavir 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 (3)
- Product Information: REYATAZ(R) oral capsules, oral powder, atazanavir oral capsules, oral powder. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2020. DailyMed
- Product Information: EVOTAZ(R) oral tablets, atazanavir cobicistat oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
- Schmidt GA, Hoehns JD, Purcell JL, et al: Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. J Am Board Fam Med 2007; 20(4):411-416. PubMed
Keep reading about Atazanavir
Keep reading about Simvastatin
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