Carbamazepine 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
Carbamazepine
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.
If you take carbamazepine (Tegretol) along with simvastatin (Zocor), the carbamazepine can speed up how fast your body breaks down the simvastatin. That means less of your cholesterol medicine stays in your bloodstream, so it may not lower your cholesterol as well as it should.
This is a well-documented effect, and the good news is that your care team can manage it. They may check your cholesterol levels and adjust your dose so it still works for you. Please don't change either medication on your own, just talk with your pharmacist or doctor so they can keep you on track.
Effect: Reduced simvastatin exposure (decreased Cmax, half-life, and AUC of simvastatin and its active metabolite simvastatin acid).
Mechanism: Carbamazepine is a strong CYP3A4 inducer; simvastatin is a CYP3A4 substrate. Induction accelerates simvastatin metabolism, lowering systemic exposure and potentially blunting lipid-lowering efficacy.
- Direction: Reduced statin effect (not toxicity).
- Onset: Delayed (enzyme induction develops over days to weeks).
- Evidence: Probable. Severity: major.
- Management: Monitor lipid panel/response; dose may need individualized upward adjustment, or consider a statin less dependent on CYP3A4.
What happens
Reduced simvastatin exposure
Interaction Deep Dive
When carBAMazepine and simvastatin are given together, the peak serum concentration, serum half-life, and AUC of both simvastatin and its active metabolite simvastatin acid were markedly decreased1. Because carBAMazepine acts as a strong CYP3A4 inducer and simvastatin serves as a CYP3A4 substrate, using them together can lower simvastatin exposure. When they are administered concurrently, monitor simvastatin levels carefully and adjust the dose as necessary23.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of simvastatin by carBAMazepine
How to manage this interaction
Here is how a care team typically handles this combination:
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may check your cholesterol (lipid) levels to see if the simvastatin is still working well.
- Your simvastatin dose may need to be adjusted and individualized by your care team, or they may consider a different cholesterol medicine that is less affected by carbamazepine.
Ask your pharmacist or doctor to review this combination, and let them know if this is a new prescription so they can plan monitoring.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Taking carBAMazepine at the same time as simvastatin markedly lowered simvastatin exposure. In a randomized crossover trial that included a 2-week washout period, 12 healthy subjects received either no drug or carBAMazepine 200 milligrams (mg) once daily for 2 days, after which the active drug group was given carBAMazepine 300 mg twice daily over the following 12 days. On day 15 (12 hours after the final carBAMazepine dose), subjects fasted for 2 hours before receiving a single 80 mg dose of simvastatin. Blood samples were collected serially immediately before and for 24 hours following simvastatin administration. Coadministration of carBAMazepine significantly decreased the mean maximum serum concentration of both simvastatin and its active metabolite simvastatin acid (from 18.7 nanograms/milliliter (ng/mL) to 6.0 ng/mL and from 3.5 ng/mL to 1.1 ng/mL, respectively; p less than 0.01 for both values). Simvastatin AUC (0-inf) fell from 88.8 ng/mL x hour to 22.6 ng/mL x hour and from 33.5 ng/mL x hour to 6.8 ng/mL x hour, respectively (p less than 0.001 for both values). Concurrent carBAMazepine also significantly shortened the mean serum half-life of simvastatin acid (from 5.9 hours to 3.7 hours, p less than 0.01) 1.
Common questions
Can I take Carbamazepine and Simvastatin together?
Carbamazepine can lower simvastatin levels and make it less effective at controlling cholesterol; keep taking both as prescribed and ask your care team to monitor your cholesterol and adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Carbamazepine 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 Carbamazepine and Simvastatin interaction managed?
Here is how a care team typically handles this combination: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may check your cholesterol (lipid) levels to see if the simvastatin is still working well. Your simvastatin dose may need to be adjusted and individualized by your care team, or they may consider a different cholesterol medicine that is less affec… 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 Carbamazepine 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 (3)
- Ucar M, Neuvonen M, Luurila H, et al: Carbamazepine markedly reduces serum concentrations of simvastatin and simvastatin acid. Eur J Clin Pharmacol 2004; 59(12):879-882. PubMed
- Product Information: Tegretol(R)-XR oral extended-release tablets, carbamazepine oral extended-release tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: Tegretol(R) oral chewable tablets, oral tablets, oral suspension, carbamazepine oral chewable tablets, oral tablets, oral suspension. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
Keep reading about Carbamazepine
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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