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Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited.
Neurogastroenterol Motil 2019; :e13617NM

Abstract

BACKGROUND

Metoclopramide is primarily a dopamine receptor antagonist, with 5HT3 receptor antagonist and 5HT4 receptor agonist activity, and used as an antiemetic and gastroprokinetic since almost 50 years. Regulatory authorities issued restrictions and recommendations regarding long-term use of the drug at oral doses exceeding 10 mg 3-4 times daily because of the risk for development of tardive dyskinesia. The aim of our study was to review mechanism(s) of action and pharmacokinetic-pharmacodynamic properties of metoclopramide, as well as the risk of metoclopramide-induced tardive dyskinesia, factors that may change drug exposure in humans, and to summarize the clinical context for appropriate use of the drug.

METHODS

A PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: drug-drug interaction, gastroparesis, metoclopramide, natural history, pharmacokinetics, pharmacodynamics, drug-drug interaction, outcome, risk factors, tardive dyskinesia.

KEY RESULTS

Data show that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years. This is far below a previously estimated 1%-10% risk suggested in treatment guidelines by regulatory authorities. High-risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications.

CONCLUSIONS & INFERENCES

The risk of tardive dyskinesia due to metoclopramide is far below approximated numbers in treatment guidelines. This risk and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis.

Authors+Show Affiliations

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Pharmacy, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31050085

Citation

Al-Saffar, Ahmad, et al. "Gastroparesis, Metoclopramide, and Tardive Dyskinesia: Risk Revisited." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 2019, pp. e13617.
Al-Saffar A, Lennernäs H, Hellström PM. Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. Neurogastroenterol Motil. 2019.
Al-Saffar, A., Lennernäs, H., & Hellström, P. M. (2019). Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, pp. e13617. doi:10.1111/nmo.13617.
Al-Saffar A, Lennernäs H, Hellström PM. Gastroparesis, Metoclopramide, and Tardive Dyskinesia: Risk Revisited. Neurogastroenterol Motil. 2019 May 2;e13617. PubMed PMID: 31050085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. AU - Al-Saffar,Ahmad, AU - Lennernäs,Hans, AU - Hellström,Per M, Y1 - 2019/05/02/ PY - 2018/11/26/received PY - 2019/04/13/revised PY - 2019/04/17/accepted PY - 2019/5/4/entrez KW - adverse effect KW - diabetes KW - dopamine KW - gastroprokinetic KW - serotonin SP - e13617 EP - e13617 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. N2 - BACKGROUND: Metoclopramide is primarily a dopamine receptor antagonist, with 5HT3 receptor antagonist and 5HT4 receptor agonist activity, and used as an antiemetic and gastroprokinetic since almost 50 years. Regulatory authorities issued restrictions and recommendations regarding long-term use of the drug at oral doses exceeding 10 mg 3-4 times daily because of the risk for development of tardive dyskinesia. The aim of our study was to review mechanism(s) of action and pharmacokinetic-pharmacodynamic properties of metoclopramide, as well as the risk of metoclopramide-induced tardive dyskinesia, factors that may change drug exposure in humans, and to summarize the clinical context for appropriate use of the drug. METHODS: A PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: drug-drug interaction, gastroparesis, metoclopramide, natural history, pharmacokinetics, pharmacodynamics, drug-drug interaction, outcome, risk factors, tardive dyskinesia. KEY RESULTS: Data show that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years. This is far below a previously estimated 1%-10% risk suggested in treatment guidelines by regulatory authorities. High-risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications. CONCLUSIONS & INFERENCES: The risk of tardive dyskinesia due to metoclopramide is far below approximated numbers in treatment guidelines. This risk and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/31050085/Gastroparesis_metoclopramide_and_tardive_dyskinesia:_Risk_revisited_ L2 - https://doi.org/10.1111/nmo.13617 DB - PRIME DP - Unbound Medicine ER -