Drug Interactions between metoclopramide and tacrolimus

MONITOR: Coadministration with gastrointestinal prokinetic agents such as cisapride, domperidone, and metoclopramide may increase the oral bioavailability of macrolide immunosuppressants. Because macrolide immunosuppressants are incompletely and variably absorbed following oral administration, increased gastrointestinal motility and gastric emptying can enhance delivery of the drugs to the small intestine where they are absorbed. In one case report, a patient with signs and symptoms of acute graft rejection in association with persistent subtherapeutic tacrolimus trough concentrations despite coadministration with ketoconazole as a pharmacokinetic booster experienced tacrolimus toxicity following the addition of metoclopramide for nausea and vomiting. Tacrolimus trough concentration exceeded 30 ng/ml, and the patient exhibited signs and symptoms suggestive of tacrolimus neuro- and nephrotoxicity. The authors theorized that the patient's persistent subtherapeutic tacrolimus levels may have been secondary to impaired gastric motility, and improvement of the condition by metoclopramide may have led to subsequent tacrolimus toxicity.

MANAGEMENT: Pharmacologic response, renal function, and macrolide immunosuppressant blood levels should be monitored more closely whenever a gastrointestinal prokinetic agent is added to or discontinue from therapy, and the immunosuppressant dosage adjusted as necessary. Patients should be advised to contact their physician if they experience potential signs and symptoms of macrolide immunosuppressant toxicity such as fever, infection, diarrhea, tremor, headache, fatigue, or lethargy.