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Tacrolimus toxicity associated with concomitant metoclopramide therapy
William A Prescott1, Brian L Callahan, Jeong M Park
1Department of Pharmacy Services, College of Pharmacy, University of Michigan Health System, Ann Arbor, Michigan 48109-0008, USA.
Pharmacotherapy
|April 22, 2004
Summary
Metoclopramide can increase tacrolimus absorption in liver transplant patients with gastric issues, leading to toxicity. Close monitoring of tacrolimus levels is crucial when these drugs are co-administered.
Area of Science:
- Pharmacology
- Transplantation Medicine
- Gastroenterology
Background:
- Subtherapeutic tacrolimus levels were observed in a liver transplant recipient.
- Standard dose adjustments and antifungal therapy failed to achieve therapeutic tacrolimus concentrations.
Observation:
- The patient developed nausea and vomiting, prompting metoclopramide administration.
- Following metoclopramide initiation and dosage increase, tacrolimus levels rapidly rose to toxic concentrations.
- Symptoms consistent with tacrolimus-induced nephrotoxicity and neurotoxicity emerged.
Findings:
- The Naranjo scale suggests metoclopramide likely caused increased tacrolimus absorption.
- Poor gastric emptying was the probable cause of baseline subtherapeutic tacrolimus levels.
- Metoclopramide improved gastric motility, enhancing tacrolimus bioavailability and causing toxicity.
Implications:
- Coadministration of metoclopramide with tacrolimus in patients with gastric dysmotility requires vigilant therapeutic drug monitoring.
- This interaction highlights the importance of considering gastric motility in tacrolimus therapy.
- Early detection and management of drug interactions are vital in post-transplant care.