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Related Experiment Videos

Diltiazem increases tacrolimus concentrations.

M F Hebert1, A Y Lam

  • 1Department of Pharmacy, University of Washington, Seattle 98195, USA. mhebert@u.washington.edu

The Annals of Pharmacotherapy
|July 20, 1999
PubMed
Summary
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Diltiazem significantly increased tacrolimus levels in a liver transplant patient, leading to toxicity. Careful monitoring and dose adjustment are crucial when these drugs are used together.

Area of Science:

  • Pharmacology
  • Transplantation Medicine
  • Clinical Pharmacy

Background:

  • Tacrolimus is a vital immunosuppressant post-orthotopic liver transplantation.
  • Drug interactions can significantly impact tacrolimus efficacy and safety.
  • Understanding drug metabolism pathways is key to managing immunosuppression.

Observation:

  • A liver transplant recipient developed elevated tacrolimus concentrations after initiating diltiazem for atrial fibrillation.
  • The patient exhibited signs of tacrolimus toxicity, including delirium and confusion.
  • Discontinuation of diltiazem and tacrolimus, followed by dose reduction, resolved the toxicity.

Findings:

  • Diltiazem inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein, key pathways for tacrolimus metabolism and transport.

Related Experiment Videos

  • This inhibition led to a more than fourfold increase in whole blood tacrolimus trough concentrations.
  • The case highlights a clinically significant drug interaction between diltiazem and tacrolimus.

    • Implications:

    • Clinicians should be aware of the potential for diltiazem to drastically increase tacrolimus levels.
    • Close monitoring of tacrolimus concentrations is essential when co-prescribing diltiazem.
    • Dose reduction of tacrolimus or avoidance of diltiazem may be necessary to prevent toxicity.