Rao AS, Camilleri M
Review article: metoclopramide and tardive dyskinesia. [JOURNAL ARTICLE]
Aliment Pharmacol Ther 2009 Nov 3.
Abstract
Background: Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA issued a black box warning regarding long-term or high-dose use of this medication because of the risk of developing tardive dyskinesia (TD).
Aims: To review the mechanism of action and pharmacokinetic (PK) properties of metoclopramide, the range of dystonias, the risk of metoclopramide-induced tardive dyskinesia and potential mechanisms that may alter PK; and to summarize the clinical context for appropriate use of the drug.
Methods: We conducted a PubMed search using the following key words and combined searches: metoclopramide, neuroleptics, TD, incidence, prevalence, dopamine, receptors, PK, pharmacology, pharmacogenetics, DRD3 Ser9Gly polymorphism, cytochrome P450, p-glycoprotein, risk factors, gastroparesis, outcome, natural history.
Results: Available data show risk of TD from metoclopramide use is likely < 1%, much less than the estimated 1-10% risk previously suggested in national guidelines. TD may represent an idiosyncratic response to metoclopramide; pharmacogenetics affect PK and dopamine receptor pharmacodynamics in response to neuroleptic agents that cause similar neurological complications.
Conclusion: Community prevalence and pharmacogenetic mechanisms involved in metoclopramide-induced TD require further study to more clearly define benefit-risk ratio.
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