Simvastatin and Efavirenz: 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
Efavirenz
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.
You're taking efavirenz (an HIV medicine) along with simvastatin (a cholesterol medicine). Here's what happens: efavirenz speeds up the body system (an enzyme called CYP3A4) that breaks down simvastatin. That means your body clears the simvastatin faster, so less of it stays in your blood.
In studies, simvastatin levels dropped by more than half when taken with efavirenz. The practical concern is that your simvastatin may not lower your cholesterol as well while you're on both. The good news is this is very manageable. Your care team can adjust your simvastatin dose and keep an eye on your cholesterol numbers to make sure it's still working. Please don't change anything on your own, just check with your doctor or pharmacist.
Effect: Reduced simvastatin exposure and attenuated lipid-lowering effect.
Mechanism: Efavirenz induces CYP3A4, accelerating simvastatin (a CYP3A4 substrate) metabolism. This is a PK interaction reducing plasma levels; not a prodrug scenario.
- Magnitude: Simvastatin Cmax reduced ~72%, AUC ~68%, Cmin ~45%; total active moiety Cmax/AUC down ~68%/60%. A separate study showed ~50%/58% reductions.
- Onset: Delayed (enzyme induction).
- Evidence: Established.
Management: Monitor lipid panel for reduced efficacy. Simvastatin dose may need to be increased/individualized to maintain LDL targets. Avoid exceeding max recommended statin dosing.
What happens
Reduced simvastatin exposure
Interaction Deep Dive
Giving efavirenz alongside simvastatin has led to lower plasma levels of simvastatin. In a group of 14 patients treated with simvastatin 40 mg once daily for 4 days in combination with efavirenz 600 mg once daily for 15 days, the simvastatin Cmax, AUC, and Cmin fell by 72%, 68%, and 45%, respectively. For the total active fraction of simvastatin (metabolites included), the Cmax and AUC dropped by 68% and 60%, respectively 1. An open-label, multidose pharmacokinetic study in healthy, HIV-seronegative volunteers found that coadministering efavirenz with simvastatin lowered simvastatin AUC values and Cmax concentrations by roughly 58% and 50%, respectively. The lipid-lowering effect of simvastatin was also diminished when it was taken together with efavirenz 2. Should these drugs be used together, adjustment of the simvastatin dose as needed should be considered 1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of simvastatin by efavirenz
How to manage this interaction
This interaction is well documented and very manageable. The main issue is that efavirenz makes simvastatin less effective, so your cholesterol may not be as well controlled.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your care team may check your cholesterol (lipid panel) to see how well the simvastatin is working.
- Your simvastatin dose may need to be adjusted and individualized by your care team to keep it effective.
What to do: Let your pharmacist or prescriber know you take both, and ask whether your cholesterol should be rechecked. Don't change your dose on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In an open-label pharmacokinetic study, giving efavirenz together with simvastatin to healthy, HIV-seronegative participants led to reduced simvastatin AUC values and plasma levels. The participants (n=13) took oral simvastatin 40 mg each night for 4 days. From day 5 through day 18, efavirenz 600 mg was given each night at bedtime. Simvastatin was resumed from day 15 to day 18. Blood samples were collected to measure the simvastatin AUC from 0 to 24 hours both before and after efavirenz was added. Simvastatin AUC values fell by a median of 58%, from 36.48 nanograms (ng) x hr/mL (95% CI, 11.63 to 58.34 ng x hr/mL) on day 3 to 14.46 ng x hr/mL (95% CI, 5.34 to 27.02 ng x hr/mL) on day 18 (p=0.0031). Median Cmax values for simvastatin were 3.52 ng/mL (95% CI, 1.21 to 4.59 ng/mL) and 1.63 ng/mL (95% CI, 0.62 to 2.61 ng/mL) on days 3 and 18, respectively (median within-subject change of -50.5%, p=0.0134). LDL changed by a median of -37 mg/dL (95% CI, -64 to -26) with simvastatin used alone. The LDL effect was diminished when efavirenz was given concurrently for 4 days (-32 mg/dL; 95% CI, -37 to -11, p=0.0476). Simvastatin does not affect the metabolism of efavirenz. One limitation of the study was the brief period (4 days) of combined efavirenz and simvastatin dosing, which restricts the ability to assess the full potential for a pharmacodynamic interaction 2.
b) When 14 patients received simvastatin 40 mg/day for 4 days along with efavirenz 600 mg/day for 15 days, the Cmax, AUC, and Cmin of simvastatin were lowered by 72%, 68%, and 45%, respectively. The Cmax and AUC of the total active moiety (including metabolites) of simvastatin decreased by 68% and 60%, respectively 1.
Common questions
Can I take Simvastatin and Efavirenz together?
Efavirenz can make simvastatin work less well by lowering its blood levels, so your cholesterol may not be fully controlled. Keep taking both as prescribed and ask your care team to monitor your cholesterol and adjust the simvastatin dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Efavirenz interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
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 Efavirenz interaction managed?
This interaction is well documented and very manageable. The main issue is that efavirenz makes simvastatin less effective, so your cholesterol may not be as well controlled. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your care team may check your cholesterol (lipid panel) to see how well the simvastatin is working. Your simvastatin dose may need to be adjusted… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
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 Efavirenz 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 anything you'd monitor while I'm on both?
References (2)
- Product Information: SUSTIVA(R) oral capsules, oral tablets, efavirenz oral capsules, oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
- Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al: Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 2005; 39(3):307-312. PubMed
Keep reading about Efavirenz
Keep reading about Simvastatin
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