Ambrisentan and Cyclosporine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclosporine
Ambrisentan
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.
What happens
Increased ambrisentan exposure
Interaction Deep Dive
In addition to other mechanisms, ambrisentan is metabolized by CYP3A4 and is also a substrate of Organic Anion Transport protein (OATP) and P-glycoprotein (P-gp)1. In a pharmacokinetic study in healthy subjects, concomitant administration of ambrisentan with cycloSPORINE, a strong inhibitor of CYP3A4, OATP, and P-gp, resulted in a 1.5-fold and 2-fold increase in ambrisentan Cmax and AUC, respectively. Therefore, if ambrisentan is coadministered with cycloSPORINE, the ambrisentan dose should not exceed 5 mg once daily 12. Do not titrate the ambrisentan dose to the recommended maximum daily dose 34.
Why it happens (mechanism)
Inhibition of ambrisentan metabolism by cycloSPORINE
Literature reports
2 reports — tap to read
a) Ambrisentan exposure increased approximately 2-fold when coadministered with cycloSPORINE in an open-label, parallel-designed pharmacokinetic study in healthy volunteers. Subjects (36 +/- 9 years old; n=24) administered oral ambrisentan 5 mg once daily for 14 days were coadministered oral cycloSPORINE (100 mg twice daily for 2 days, then titrated in 25-mg increments to achieve a cycloSPORINE trough level of 150 to 200 nanograms (ng)/mL; maximum allowable dose 150 mg twice daily), on days 6 through 14. The geometric mean AUC of ambrisentan administered alone (day 4) was 3109 ng x hr/mL, then increased by 40% (4360 ng x hr/mL) and 58% (4907 ng x hr/mL) on days 6 and 7, respectively, when coadministered with cycloSPORINE. On day 14 (steady state of cycloSPORINE), the ambrisentan steady state geometric mean Cmax increased by 48% (421 ng/mL to 624 ng/mL), Cmin increased 3.4-fold (28.6 ng/mL to 96.2 ng/mL), and AUC increased by more than 2-fold (2952 ng x hr/mL to 6535 ng x hr/mL). In a second study (n=28), the addition of ambrisentan to cycloSPORINE did not have a clinically significant effect on cycloSPORINE pharmacokinetics. With concurrent administration of ambrisentan and cycloSPORINE, the authors recommend limiting the ambrisentan dose to 5 mg once daily 2.
b) In a drug interaction study, coadministration of ambrisentan (5 mg daily) and cycloSPORINE (100 to 150 mg twice daily initially, then dosing to achieve Cmin 150 to 200 ng/mL) for 8 days in healthy subjects resulted mean increases in ambrisentan AUC and Cmax of approximately 2-fold and 1.5-fold, respectively, compared to ambrisentan alone 34.
Common questions
Can I take Ambrisentan and Cyclosporine together?
Increased ambrisentan exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ambrisentan and Cyclosporine interaction?
It is rated major. Potentially serious — often needs a change or close 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 strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ambrisentan or Cyclosporine 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: LETAIRIS(R) oral tablets, ambrisentan oral tablets. Gilead Sciences, Inc. Foster City, CA, 2010. DailyMed
- Spence R, Mandagere A, Richards DB, et al: Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther 2010; 88(4):513-520. PubMed
- Product Information: NEORAL(R) oral soft gelatin capsules oral solution, cyclosporine modified oral soft gelatin capsules oral solution. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: SANDIMMUNE(R) oral capsules, oral solution, intravenous injection, cyclosporine oral capsules, oral solution, intravenous injection. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
Keep reading about Cyclosporine
Keep reading about Ambrisentan
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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