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Serious interaction between mibefradil and tacrolimus

S Krähenbühl1, A Menafoglio, E Giostra

  • 1Institute of Clinical Pharmacology, University of Berne, Switzerland. skraehen@ikp.unibe.ch

Transplantation
|November 10, 1998
PubMed
Summary
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Mibefradil significantly increases tacrolimus blood levels by inhibiting its metabolism. This drug interaction can lead to tacrolimus toxicity, necessitating avoidance of mibefradil in patients on tacrolimus therapy.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Toxicology

Background:

  • Tacrolimus, an immunosuppressant, is metabolized by cytochrome P450 3A4 and 2D6.
  • Tacrolimus possesses a narrow therapeutic index, requiring careful monitoring.
  • Mibefradil is a potent inhibitor of cytochrome P450 enzymes.

Observation:

  • A liver transplant recipient on tacrolimus experienced toxicity after initiating mibefradil for hypertension.
  • Symptoms included mental confusion, renal failure, and hyperglycemia, coinciding with a tacrolimus blood concentration of 100 ng/ml.
  • Discontinuation of mibefradil led to patient recovery and normalization of tacrolimus levels.

Findings:

  • Mibefradil inhibits the metabolism of tacrolimus.
  • This inhibition results in a substantial increase in tacrolimus blood concentration.

Related Experiment Videos

  • The observed interaction highlights a significant pharmacokinetic issue.

    • Implications:

    • Mibefradil should not be co-administered with tacrolimus.
    • Clinicians must be aware of potential drug interactions involving cytochrome P450 inhibitors.
    • Patient safety requires careful medication review in transplant recipients.