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Meta-Analysis
. 2023 Mar;23(1):1-20.
doi: 10.1007/s40268-023-00413-x. Epub 2023 Feb 7.

Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis

Daniela R Junqueira  1 , Dimitri Bennett  2   3 , Susanna Y Huh  4   5 , Kyle Fahrbach  6 , Binod Neupane  1 , Marissa Betts  6
Affiliations
Meta-Analysis

Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis

Daniela R Junqueira et al. Drugs R D. 2023 Mar.

Abstract

Background: Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis.

Methods: We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI).

Results: We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs.

Conclusions: The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions.

Registration: PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).

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Conflict of interest statement

Dr. Bennett and Dr. Huh are current and former employees, respectively, of Takeda Development Center Americas, Inc., and received stock or stock options at the time of study. Currently, Dr. Huh is with Ironwood Pharmaceuticals. Dr. Junqueira, Ms. Betts, Dr. Fahrbach, and Dr. Neupane provided consultancy support to Takeda Development Center Americas, Inc., as employees of Evidera.

Figures

Fig. 1
Fig. 1
PRISMA diagram
Fig. 2
Fig. 2
Meta-analysis of cardiovascular adverse events among patients treated with domperidone. FE model. Results of sensitivity analysis for QTc prolongation removing an outlier study with longer treatment duration [46]. CI confidence interval, FE fixed effects, QTc heart rate-corrected QT
Fig. 3
Fig. 3
Meta-analysis of extrapyramidal adverse effects among patients treated with metoclopramide—restlessness. CI confidence interval, FE fixed effects
Fig. 4
Fig. 4
Meta-analysis of extrapyramidal adverse events among patients treated with metoclopramide compared with placebo—restlessness. CI confidence interval, FE fixed effects, MET metoclopramide, PLC placebo
Fig. 5
Fig. 5
Meta-analysis of endocrine adverse events among patients treated with domperidone. CI confidence interval, FE fixed effects
Fig. 6
Fig. 6
Meta-analysis of endocrine adverse events among patients treated with metoclopramide—hypoglycemia. CI confidence interval, FE fixed effects
See this image and copyright information in PMC

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