Download Suggestion from clinicians

Domperidone
To replace metoclopramide
Explanation for replacement:
Suggestion from clinicians: “Domperidone (less EPS)”
CLEAN Meds antiemetic agent
 metoclopramide
Literature Review Question
Is domperidone superior to metoclopramide in terms of effectiveness and safety for treatment of
gastrointestinal dysmotility?
Literature search
Utilized electronic databases: PubMed, Cochrane
Brief search strategies: (systematic review filter) AND (metoclopramide or domperidone)
Furyk JS, Meek RA, Egerton-Warburton D. Drugs for the treatment of nausea and
vomiting in adults in the emergency department setting. Cochrane Database Syst Rev. 2015 Sep
28;(9):CD010106.
Objective
“Provide evidence of the efficacy and safety of antiemetic medications in the management of nausea and
vomiting in the adult ED setting”
Studies Included
Study included eight trials, involving 952 participants, of which 64% were women. Primary outcome
were reported as mean change in visual analogue scale (VAS) (0 to 100) for nausea severity from baseline
to 30 minutes. “Differences in mean VAS change from baseline to 30 minutes between placebo and the
drugs evaluated were: metoclopramide, ondansetron, prochlorperazine, promethazine and droperidol.
Results
“The only statistically significant change in baseline VAS to 30 minutes was for droperidol, in a single
trial of 48 participants. No other drug was statistically significantly superior to placebo.”
Comparison 1 Metoclopramide versus placebo, Outcome 1 Change in nausea severity at 30min.
“All three trials evaluated metoclopramide and included 299 participants (Barrett 2011; Braude 2006;
Egerton-Warburton 2014). The pooled outcome versus placebo favoured metoclopramide (OR 0.3, 95%
CI 0.17 to 0.53)”
Comparison 1 Metoclopramide versus placebo, Outcome 2 Proportion of participants requiring rescue
medication.
Adverse Events
“All three trials that investigated metoclopramide reported adverse reactions, however, differences in
reporting precluded pooling of results. None of the trials reported any serious adverse events.”
“Barrett 2011, evaluating ondansetron, metoclopramide and promethazine versus placebo, separately
reported the proportion of participants with akathisia, headache and sedation at baseline and 30 minutes.
These symptoms were commonly reported at baseline making interpretation of 30-minute data
problematic. At 30 minutes, akathisia was more common with each drug compared with placebo (4/38
(11%) with ondansetron, 11/41 (27%) with metoclopramide, 2/43 (5%) with promethazine, 1/38 with
placebo). Headache was reported by 11/39 (28%) participants with ondansetron, 8/41 (20%) with
metoclopramide and 12/43 (28%) with promethazine, compared with 6/38 (16%) with placebo. Sedation
was reported by 16/39 (41%) participants with ondansetron, 21/40 (53%) with metoclopramide and 25/43
(58%) with promethazine, compared with 13/38 (34%) with placebo.”
“Egerton-Warburton 2014 reported adverse events in 9/258 (3.5%) participants: six in participants who
received metoclopramide (two akathisia, two restlessness, one sweatiness and one muscle twitching), two
in participants who received ondansetron (one dizziness and one stinging at injection site) and one in a
participant who received placebo (shaking and restlessness).”
Roy, P., N.H. Patel, and A.J. Miller, A comparison of controlled release metoclopramide and
domperidone in the treatment of nausea and vomiting. Br J Clin Pract, 1991. 45(4): p. 247-51.
*ABSTRACT ONLY*.
Objective
Direct comparison of the safety and efficacy of metoclopramide and domperidone
Study group
RCT, parallel group comparative study involving 95 patients with symptoms of nausea and vomiting due
to variety of oesophageal or gastric disorders. Comparative study of controlled release metoclopramide
15 mg given twice daily, and domperidone 10 mg or 20 mg given three times daily. Patients were
randomly allocated to one of the three treatment regimes for a period of seven days, throughout which
daily symptomatology and use of escape medication were recorded on a diary card.
Results
“Both controlled release metoclopramide and high and low dose domperidone significantly reduced
symptoms of belching, flatulence, distension, heartburn, regurgitation, reflux, nausea and vomiting
compared to baseline. There were no significant differences between the three treatments in efficacy or in
the number and severity of side-effects.”
DeCamp, L.R., et al., Use of antiemetic agents in acute gastroenteritis: a systematic review and metaanalysis. Arch Pediatr Adolesc Med, 2008. 162(9): p. 858-65.
Objective:
Does taking taking antiemetic drugs reduce vomiting and decreases the need for further intervention in
children with gastroenteritis without causing significant adverse effects?
Data sources:
Prospective controlled trials evaluating medication use in children with vomiting from gastroenteritis.
11 articles were included in this review: ondansetron (n = 6), domperidone (n = 2), trimethobenzamide (n
= 2), pyrilamine-pentobarbital (n = 2), metoclopramide (n = 2), dexamethasone (n = 1), and promethazine
(n = 1).
Main outcome measures:
Emesis cessation, use of intravenous fluid for rehydration, hospital admission, return to care, and
medication adverse effects.
Outcomes with domperidone
“Two studies of domperidone suppositories for the treatment of vomiting in hospitalized children met the
inclusion criteria. These studies reported results for 109 children with vomiting, although enrollment was
not limited to patients with gastroenteritis. Both studies demonstrated that domperidone decreased the
symptoms of nausea and vomiting compared with placebo. Neither trial reported any adverse events or
medication adverse effects.”
Outcomes with metoclopramide
“Two included studies evaluated metoclopramide as a treatment for vomiting associated with
gastroenteritis in 96 hospitalized children. One study found metoclopramide to be more effective than
placebo at reducing symptoms of nausea and vomiting. No adverse events were reported. The second
study found that metoclopramide did not reduce emetic episodes relative to placebo. Reported adverse
effects in patients who received metoclopramide included drowsiness, cough, and tremor.”
Lau Moon Lin, M., et al., The Safety of Metoclopramide in Children: A Systematic Review and MetaAnalysis. Drug Saf, 2016. 39(7): p. 675-87.
Aim
Describes safety of metoclopramide in children (<18 years) given for any indication
Studies included
A total of 108 (57 prospective) studies involving 2699 patients (2745 metoclopramide courses) were
included.
Results
“The most common adverse effects reported in prospective studies of metoclopramide in children were
extrapyramidal symptoms (EPS; 9 %, 95 % confidence interval [CI] 5–17), diarrhea (6 %, 95 % CI 4–9),
and sedation (multiple-dose studies: 6 %, 95 % CI 3–12). The mean proportion of children experiencing
EPS was higher in studies where EPS prophylaxis was administered than in those in which it was not (24 %
[95 % CI 13–43] vs. 7 % [95 % CI 3–15]; p = 0.01)”
“Dysrhythmia, respiratory distress/arrest, neuroleptic malignant syndrome, and tardive dyskinesia were
rarely associated with metoclopramide use.”
“Life-threatening adverse effects associated with metoclopramide administration were rarely reported:
repeated apnea and anaphylaxis were each reported in one child. No adverse effect was reported that was
irreversible or slow to resolve.”
Figure below: Forest plots: meta-analysis of extrapyramidal symptoms associated with multiple dose
metoclopramide use in children. a All prospective studies. b Studies with and without extrapyramidal
symptoms prophylaxis. CI confidence interval, EPS extrapyramidal symptoms, SE standard error
Patterson, D., et al., A double-blind multicenter comparison of domperidone and metoclopramide in
the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol, 1999. 94(5): p.
1230-4.
Objective:
A double-blind, multicenter, randomized trial to compare the side effects and efficacy of domperidone
and metoclopramide in symptomatic diabetic gastroparesis.
Methods
“93 insulin-dependent diabetes patients with 3 month history of gastroparesis. 48 received domperidone,
45 received metoclopramide + 1 placebo tablet 4x daily. Nausea, vomiting, bloating/distension, and early
satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of
somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded
for severity at 2 and 4 wk.”
Results:
“Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic
gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide.
Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of
metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone
(incidence, p= 0.02; severity; p= 0.03). A reduction in mental acuity was acknowledged by 33% of
patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean
severity score, 0.27) after 4 wk of domperidone (incidence, p= 0.04; severity, p= 0.04). Akathisia,
asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of
domperidone, although these differences were not statistically significant.”
Complete search strategies
PubMed (n=110)
(((systematic review [ti] OR meta-analysis [pt] OR meta-analysis [ti] OR systematic literature review [ti]
OR this systematic review [tw] OR pooling project [tw] OR (systematic review [tiab] AND review [pt])
OR meta synthesis [ti] OR meta synthesis [ti] OR integrative review [tw] OR integrative research review
[tw] OR rapid review [tw] OR consensus development conference [pt] OR practice guideline [pt] OR
drug class reviews [ti] OR cochrane database syst rev [ta] OR acp journal club [ta] OR health technol
assess [ta] OR evid rep technol assess summ [ta] OR jbi database system rev implement rep [ta]) OR
(clinical guideline [tw] AND management [tw]) OR ((evidence based[ti] OR evidence-based medicine
[mh] OR best practice* [ti] OR evidence synthesis [tiab]) AND (review [pt] OR diseases category[mh]
OR behavior and behavior mechanisms [mh] OR therapeutics [mh] OR evaluation studies[pt] OR
validation studies[pt] OR guideline [pt] OR pmcbook)) OR ((systematic [tw] OR systematically [tw] OR
critical [tiab] OR (study selection [tw]) OR (predetermined [tw] OR inclusion [tw] AND criteri* [tw]) OR
exclusion criteri* [tw] OR main outcome measures [tw] OR standard of care [tw] OR standards of care
[tw]) AND (survey [tiab] OR surveys [tiab] OR overview* [tw] OR review [tiab] OR reviews [tiab] OR
search* [tw] OR handsearch [tw] OR analysis [ti] OR critique [tiab] OR appraisal [tw] OR (reduction
[tw]AND (risk [mh] OR risk [tw]) AND (death OR recurrence))) AND (literature [tiab] OR articles [tiab]
OR publications [tiab] OR publication [tiab] OR bibliography [tiab] OR bibliographies [tiab] OR
published [tiab] OR pooled data [tw] OR unpublished [tw] OR citation [tw] OR citations [tw] OR
database [tiab] OR internet [tiab] OR textbooks [tiab] OR references [tw] OR scales [tw] OR papers [tw]
OR datasets [tw] OR trials [tiab] OR meta-analy* [tw] OR (clinical [tiab] AND studies [tiab]) OR
treatment outcome [mh] OR treatment outcome [tw] OR pmcbook)) NOT (letter [pt] OR newspaper
article [pt]))) OR ((randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [tiab]
OR placebo [tiab] OR clinical trials as topic [mesh: noexp] OR randomly [tiab] OR trial [ti]) NOT
(animals [mh] NOT humans [mh])) AND (domperidone OR domperidon[MeSH Terms]) AND
(metoclopramide OR metoclopramide[MeSH Terms])
Cochrane (n=130)
#1
domperidone
#2
domperidon
#3
MeSH descriptor: [Domperidone] explode all trees
#4
metoclopramide
#5
MeSH descriptor: [Metoclopramide] explode all trees
#6
(#1 or #2 or #3) and (#4 or #5)