Bosentan 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
Bosentan
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.
If you take bosentan (a medicine for pulmonary high blood pressure) along with simvastatin (a cholesterol medicine), you should know that bosentan can make your body clear out simvastatin faster. In studies, the amount of active simvastatin in the blood dropped by about half. That means your cholesterol medicine may not lower your cholesterol as well as it should.
The good news is this is very manageable. Your care team can simply check your cholesterol levels and, if needed, adjust your simvastatin dose so it keeps working for you. Please don't stop or change either medicine on your own. Just bring it up with your pharmacist or doctor.
Effect: Bosentan induces CYP3A4, increasing simvastatin metabolism and reducing exposure of simvastatin and its active beta-hydroxy acid metabolite by roughly 50%. Bosentan concentrations are unaffected. Net result is reduced lipid-lowering efficacy.
- Direction: Decreased simvastatin plasma levels (enzyme induction, not a prodrug issue).
- Onset: Rapid.
- Evidence: Probable.
- Severity: Moderate.
- Management: Monitor lipid panel; the simvastatin dose may need to be uptitrated and individualized to achieve target LDL. Consider a statin less dependent on CYP3A4 if goals are not met.
What happens
Reduced plasma concentrations and reduced efficacy of simvastatin
Interaction Deep Dive
When bosentan was given together with simvastatin, the plasma levels of simvastatin and of its active beta-hydroxy acid metabolite fell by roughly 50%. Bosentan plasma levels showed no change. Clinicians should keep in mind that simvastatin efficacy may be diminished12.
Why it happens (mechanism)
Induction of cytochrome P4503A4-mediated metabolism of simvastatin
How to manage this interaction
This interaction is manageable, and both medicines can usually be taken together.
- Keep taking both as prescribed unless your care team tells you otherwise.
- Your team will likely check your cholesterol (lipid panel) to make sure the simvastatin is still working well.
- Your simvastatin dose may need to be adjusted and individualized by your care team to keep your cholesterol at goal.
- Ask your pharmacist or doctor whether your cholesterol numbers are on target, and mention any new medicines you start.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving bosentan together with simvastatin decreases exposure to both simvastatin and beta-hydroxyacid simvastatin. Nine healthy male participants took part in a single-center, open-label, randomized, three-way crossover study. Three separate treatment sequences were used, each separated by a washout interval of 2 weeks. The 3 treatments consisted of: (A) bosentan 125 mg twice daily for 5.5 days; (B) simvastatin 40 mg once daily for 6 days; (C) bosentan 125 mg twice daily and simvastatin 40 mg once daily for 5.5 and 6 days, respectively. Simultaneous administration of bosentan lowered exposure to simvastatin and beta-hydroxyacid simvastatin by 34 and 46%, respectively, and these values were significant. No statistically significant effect was seen on the Cmax of either compound. This indicates that bosentan's influence on simvastatin metabolism arises from interference at the systemic rather than the presystemic level 1.
Common questions
Can I take Bosentan and Simvastatin together?
Bosentan can cut simvastatin's blood levels by about half and weaken its cholesterol-lowering effect, so your care team may check your cholesterol and adjust your simvastatin dose. Keep taking both as prescribed and follow up with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Bosentan and Simvastatin interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Bosentan and Simvastatin interaction managed?
This interaction is manageable, and both medicines can usually be taken together. Keep taking both as prescribed unless your care team tells you otherwise. Your team will likely check your cholesterol (lipid panel) to make sure the simvastatin is still working well. Your simvastatin dose may need to be adjusted and individualized by your care team to keep your cholesterol at goal. Ask your pharmac… 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 Bosentan 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 anything you'd monitor while I'm on both?
References (2)
- Dingemanse J, Schaarschmidt D, & van Giersbergen P: Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet 2003; 42(3):293-301. PubMed
- Product Information: Tracleer(TM), bosentan. Actelion Pharmaceuticals US, Inc. South San Francisco, CA, 2001. DailyMed
Keep reading about Bosentan
Keep reading about Simvastatin
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