Rifampin 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
Rifampin
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.
Let's talk about taking rifampin and simvastatin together. Rifampin is a strong 'speed-up' medicine for your liver. It tells your body to break down simvastatin much faster than normal, so a lot less of the cholesterol medicine stays in your blood. In one study, the amount of active simvastatin dropped by more than half, and sometimes by almost all of it.
What does that mean for you? Your simvastatin may not lower your cholesterol as well while you are on rifampin. This is very manageable. Keep taking both as prescribed, and let your doctor or pharmacist know you are on both so they can check your cholesterol and adjust your plan if needed.
Effect: Rifampin markedly reduces simvastatin exposure via induction of CYP3A4-mediated metabolism, lowering both parent drug and active simvastatin acid and reducing lipid-lowering efficacy.
- Direction/magnitude: Reduced effect. AUC reduced ~56-94% (simvastatin) and ~82-97% (simvastatin acid) in a crossover study after 5-day rifampin pretreatment.
- Onset: Delayed (enzyme induction develops over days).
- Evidence: Probable; severity major.
- Management: Monitor lipid panel for loss of efficacy. Dose may need to be individualized; consider a statin less dependent on CYP3A4 if durable dual therapy is required, per prescriber judgment.
What happens
Reduced simvastatin exposure and reduced efficacy of simvastatin
Interaction Deep Dive
Caution is warranted when rifAMPin is given together with agents that undergo cytochrome P450 metabolism, including simvastatin1. When rifAMPin and simvastatin are used together, simvastatin exposure may be lowered 231. As a result, concurrent rifAMPin may diminish the cholesterol-lowering effectiveness of simvastatin. In a randomized, placebo-controlled cross-over investigation comprising two phases separated by a 4-week washout period, ten volunteers were studied. Participants were pretreated for 5 days with either rifAMPin (600 mg daily) or placebo. A single oral 40 mg dose of simvastatin was then given on day 6. RifAMPin lowered plasma levels of simvastatin as well as its active metabolite, simvastatin acid. The decrease in total area under the concentration-time curve (AUC) was between 56% and 94% for simvastatin and between 82% and 97% for simvastatin acid 4.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
Rifampin can make simvastatin work less well by clearing it from your body faster. The good news is your care team can manage this.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may check your cholesterol more closely to see if the statin is still doing its job.
- Your simvastatin dose may need to be adjusted and individualized, or your prescriber may consider a different cholesterol medicine, based on your results.
- Tell your pharmacist and doctor that you take both, especially if the rifampin is only for a short course.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In an interaction study, ten volunteers were entered into a randomized, placebo-controlled, cross-over design consisting of two phases separated by a washout interval of 4 weeks. Participants underwent a 5-day pretreatment period with rifAMPin (600 mg daily) or placebo. On day 6, a single oral 40 mg dose of simvastatin was given. RifAMPin lowered plasma levels of simvastatin and of its active metabolite simvastatin acid. The decrease in the total area under the concentration-time curve (AUC) ranged from 56% to 94% for simvastatin and from 82% to 97% for simvastatin acid 4
Common questions
Can I take Rifampin and Simvastatin together?
Rifampin can significantly weaken simvastatin's cholesterol-lowering effect by speeding up its breakdown; keep taking both as prescribed and ask your care team to monitor your cholesterol and adjust your plan if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rifampin and Simvastatin interaction?
It is rated major. Potentially serious — often needs a change or close 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 Rifampin and Simvastatin interaction managed?
Rifampin can make simvastatin work less well by clearing it from your body faster. The good news is your care team can manage this. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may check your cholesterol more closely to see if the statin is still doing its job. Your simvastatin dose may need to be adjusted and individualized, or your prescriber may consi… 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 Rifampin 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 (4)
- Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFADIN(R) IV intravenous injection, rifampin intravenous injection. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFADIN(R) oral capsules, rifampin oral capsules. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Kyrklund C, Backman J, Kivisto K, et al: Rifampin greatly reduces plasma simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 2000; 68(6):592-597. PubMed
Keep reading about Rifampin
Keep reading about Simvastatin
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