Tacrolimus Toxicity Associated with Concomitant Metoclopramide Therapy
- 1 April 2004
- journal article
- case report
- Published by Wiley in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Vol. 24 (4), 532-537
- https://doi.org/10.1592/phco.24.5.532.33357
Abstract
Subtherapeutic tacrolimus trough concentrations were noted in a 52‐year‐old woman who had undergone liver transplantation. Her tacrolimus dosage was increased from 7 to 28 mg twice/day, and ketoconazole therapy was added; however, her tacrolimus concentration remained undetectable. Metoclopramide 10 mg 4 times/day was begun to control the patient's new‐onset nausea and vomiting. Within 48 hours of increasing the dosage to 20 mg 4 times/day, her tacrolimus trough concentration exceeded 30 ng/ml. Signs and symptoms were suggestive of tacrolimus nephrotoxicity and neurotoxicity. According to the Naranjo scale, this adverse drug event was probably the result of improved absorption of tacrolimus secondary to metoclopramide therapy. The patient's subtherapeutic tacrolimus concentration at baseline was probably secondary to poor absorption due to impaired gastric emptying. Coadministration of metoclopramide significantly improved gastric motility and delivery of tacrolimus to the small intestine, increasing tacrolimus bioavailability, thus resulting in acute‐onset tacrolimus toxicity. When tacrolimus is administered with metoclopramide in patients with gastric dysmotility, tacrolimus concentrations should be monitored closely to minimize the risk of toxicity.This publication has 20 references indexed in Scilit:
- Two‐ to three‐fold increase in blood tacrolimus (FK506) levels during diarrhea in liver‐transplanted childrenClinical Transplantation, 2003
- Differential Effect of Diarrhea on FK506 Versus Cyclosporine A Trough Levels and Resultant Prevention of Allograft Rejection in Renal Transplant RecipientsAmerican Journal of Transplantation, 2002
- Mechanisms of Clinically Relevant Drug Interactions Associated with TacrolimusClinical Pharmacokinetics, 2002
- Renal Allograft Dysfunction Associated with Rifampin–Tacrolimus InteractionAnnals of Pharmacotherapy, 2000
- Tacrolimus oral bioavailability doubles with coadministration of ketoconazole*Clinical Pharmacology & Therapeutics, 1997
- Clinical Pharmacokinetics of TacrolimusClinical Pharmacokinetics, 1995
- Tacrolimus: a new immunosuppressive agentAmerican Journal of Health-System Pharmacy, 1995
- FK506 TROUGH LEVELS IN WHOLE BLOOD AND PLASMA IN LIVER TRANSPLANT RECIPIENTSTransplantation, 1994
- THE EFFECT OF ORAL METOCLOPRAMIDE ON THE ABSORPTION OF CYCLOSPORINETransplantation, 1987
- A method for estimating the probability of adverse drug reactionsCancer Cell, 1981