PMID- 36749528
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230307
IS  - 1179-6901 (Electronic)
IS  - 1174-5886 (Print)
IS  - 1174-5886 (Linking)
VI  - 23
IP  - 1
DP  - 2023 Mar
TI  - Risk of Adverse Events Associated with Domperidone and Metoclopramide in 
      Gastroparesis: Systematic Review and Meta-analysis.
PG  - 1-20
LID - 10.1007/s40268-023-00413-x [doi]
AB  - 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).
CI  - (c) 2023. The Author(s).
FAU - Junqueira, Daniela R
AU  - Junqueira DR
AD  - Evidera, a part of Thermo Fisher Scientific, Montreal, QC, Canada.
FAU - Bennett, Dimitri
AU  - Bennett D
AUID- ORCID: 0000-0002-8387-9342
AD  - Takeda Development Center Americas, Inc., 35 Landsdowne St, Cambridge, MA, 02139, 
      USA. Dimitri.bennett@takeda.com.
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 
      Dimitri.bennett@takeda.com.
FAU - Huh, Susanna Y
AU  - Huh SY
AD  - Takeda Development Center Americas, Inc., 35 Landsdowne St, Cambridge, MA, 02139, 
      USA.
AD  - Ironwood Pharmaceuticals, Boston, MA, USA.
FAU - Fahrbach, Kyle
AU  - Fahrbach K
AD  - Evidera, a part of Thermo Fisher Scientific, Waltham, MA, USA.
FAU - Neupane, Binod
AU  - Neupane B
AD  - Evidera, a part of Thermo Fisher Scientific, Montreal, QC, Canada.
FAU - Betts, Marissa
AU  - Betts M
AD  - Evidera, a part of Thermo Fisher Scientific, Waltham, MA, USA.
LA  - eng
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20230207
PL  - New Zealand
TA  - Drugs R D
JT  - Drugs in R&D
JID - 100883647
RN  - 5587267Z69 (Domperidone)
RN  - L4YEB44I46 (Metoclopramide)
RN  - 0 (Dopamine Antagonists)
SB  - IM
MH  - Adult
MH  - Child
MH  - Humans
MH  - *Domperidone/adverse effects
MH  - Metoclopramide/adverse effects
MH  - *Gastroparesis/chemically induced/drug therapy
MH  - Dopamine Antagonists/adverse effects
PMC - PMC9985532
COIS- 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.
EDAT- 2023/02/08 06:00
MHDA- 2023/03/08 06:00
PMCR- 2023/02/07
CRDT- 2023/02/07 11:22
PHST- 2023/01/22 00:00 [accepted]
PHST- 2023/02/08 06:00 [pubmed]
PHST- 2023/03/08 06:00 [medline]
PHST- 2023/02/07 11:22 [entrez]
PHST- 2023/02/07 00:00 [pmc-release]
AID - 10.1007/s40268-023-00413-x [pii]
AID - 413 [pii]
AID - 10.1007/s40268-023-00413-x [doi]
PST - ppublish
SO  - Drugs R D. 2023 Mar;23(1):1-20. doi: 10.1007/s40268-023-00413-x. Epub 2023 Feb 7.