Mibefradil and Cyclosporine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclosporine Injection
Mibefradil
No brand names on record
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 cycloSPORINE exposure and an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias)
Interaction Deep Dive
Coadministration of cycloSPORINE (a P-gp substrate) with mibefradil (a P-gp inhibitor) may increase the concentrations of cycloSPORINE12. Also, concomitant use of mibefradil (50 mg for eight days), a drug which inhibits cytochrome P450 3A4 (CYP3A4), and cycloSPORINE, a drug metabolized by CYP3A4, has resulted in a two-fold increase in the cycloSPORINE concentration 53. Adjust cycloSPORINE dosage to achieve the desired cycloSPORINE concentrations when these drugs are administered concomitantly 12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated cycloSPORINE metabolism; inhibition of P-gp-mediated efflux transport of cycloSPORINE
Literature reports
2 reports — tap to read
a) Six renal transplant recipients stabilized on cycloSPORINE participated in an open-label study to evaluate the effects of cycloSPORINE and mibefradil coadministration. Mibefradil 25 mg was administered on the first day, and the dose was increased to 50 mg daily for five or six more days. CycloSPORINE had no significant effect on the plasma concentrations of mibefradil. However, mibefradil did increase cycloSPORINE plasma concentrations by more than 2-fold. Maximum concentrations (Cmax) of cycloSPORINE averaged 477 ng/mL prior to the administration of mibefradil and increased to 986 ng/mL following mibefradil therapy. Similarly, minimum concentration (Cmin) of cycloSPORINE increased from 125 ng/mL to 340 ng/mL. CycloSPORINE AUC rose from 2778 ng/mL/h to 6458 ng/mL/h when mibefradil was coadministered. Mibefradil is an inhibitor of cytochrome P450 3A4 enzymes, which metabolize cycloSPORINE 3.
b) A 47-year-old male kidney transplant recipient treated with simvastatin 40 mg daily and cycloSPORINE for two weeks experienced rhabdomyolysis one month after mibefradil 50 mg daily was added to therapy. He was admitted to the hospital following complaints of progressive muscle weakness, myalgia, hematuria, and oliguria. Admission laboratory values included CPK 150,698 U/L, LDH 2986 U/L, creatinine 4.8 mg/dL, and SGOT 3101 U/L. Prior to this episode, his cycloSPORINE levels were stabilized between 94 and 209 ng/mL. On admit, his cycloSPORINE trough was measured at 559 ng/mL. This patient's rhabdomyolysis was attributed to mibefradil's inhibition of cytochrome P450 3A4-mediated cycloSPORINE and simvastatin metabolism 4.
Common questions
Can I take Mibefradil and Cyclosporine Injection together?
Increased cycloSPORINE exposure and an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mibefradil and Cyclosporine Injection 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 strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Mibefradil or Cyclosporine Injection 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 (5)
- 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
- Spoendlin M, Peters J, Welker H, et al: Pharmacokinetic interaction between oral cyclosporin and mibefradil in stabilized post-renal-transplant patients. Nephrol Dial Transplant 1998; 13:1787-1791. PubMed
- Wombolt DG, Jackson A, Punn R, et al: Case report: rhabdomyolysis induced by mibefradil in a patient treated with cyclosporine and simvastatin. J Clin Pharmacol 1999; 39:310-312. DOI
- Product Information: Posicor(R), mibefradil dihydrochloride. Roche Laboratories Inc. Nutley, NJ, 1997.
Keep reading about Cyclosporine Injection
Keep reading about Mibefradil
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