Background/aims: Tacrolimus is metabolized by cytochrome P450 3A4 and 2D6 and has a narrow therapeutic range. We report a serious kinetic interaction between tacrolimus and mibefradil, a potent cytochrome P450 inhibitor.
Case Report: A 62-year-old women who had undergone liver transplantation was treated with tacrolimus for immunosuppression. For control of blood pressure, the patient was treated with nifedipine. She developed ankle edema, and nifedipine was replaced by mibefradil. Four days later, she presented with mental confusion, renal failure, and hyperglycemia, compatible with tacrolimus toxicity. In agreement with this assumption, the tacrolimus blood concentration was 100 ng/ml. Mibefradil and tacrolimus were both stopped, and the patient recovered within 1 week. Eight days after stopping mibefradil, tacrolimus was restarted at the same dosage and the subsequent plasma concentrations remained in the therapeutic range.
Conclusions: Mibefradil increases the tacrolimus blood concentration by inhibiting its metabolism and should, therefore, not be used in patients treated with tacrolimus.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/00007890-199810270-00026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mycophenolate mofetil decreases endothelial prostaglandin E2 in response to allogeneic T cells or cytokines.
Transplantation
May 2000
Department of General Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Background: Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release.
View Article and Find Full Text PDFTacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation.
Z Gastroenterol
October 1999
Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Humboldt-Universität zu Berlin, Germany.
A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels.
View Article and Find Full Text PDFSerious interaction between mibefradil and tacrolimus.
Transplantation
October 1998
Institute of Clinical Pharmacology, University of Berne, Switzerland.
Background/aims: Tacrolimus is metabolized by cytochrome P450 3A4 and 2D6 and has a narrow therapeutic range. We report a serious kinetic interaction between tacrolimus and mibefradil, a potent cytochrome P450 inhibitor.
Case Report: A 62-year-old women who had undergone liver transplantation was treated with tacrolimus for immunosuppression.
Roche, FDA announce new drug-interaction warnings for mibefradil.
Am J Health Syst Pharm
February 1998
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!