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Journal of Human Lactation : Official... Feb 2015Breastfeeding is the optimal method for feeding a newborn. However, some mothers may have difficulties lactating. Domperidone is widely used as a galactagogue but to the... (Review)
Review
Breastfeeding is the optimal method for feeding a newborn. However, some mothers may have difficulties lactating. Domperidone is widely used as a galactagogue but to the best of our knowledge has not been approved by any health authority. The objective of this review was to assess the benefit-risk ratio of domperidone for stimulating lactation. The benefit-risk ratio of domperidone as a galactagogue was assessed following a literature search of the PubMed database up to July 2013. Four studies were selected to assess domperidone efficacy and demonstrated an increased milk production. The limited data (60 mother-baby pairs) and the moderate methodological quality of 1 study remain insufficient to conclude on domperidone efficacy. Regarding the safety of domperidone, 7 studies were selected that exposed 113 infants to domperidone through breastfeeding. No adverse effects were observed in 85 infants, and no information was provided for the remaining 28. The limited data available remain in favor of a safe domperidone profile in infants and mothers. However, in large studies focused on gastrointestinal disorders, domperidone is responsible for drug-induced long QT syndrome and sudden cardiac death. The use of domperidone as a galactagogue is worrisome as drug-induced long QT syndrome occurred mostly in women. In these circumstances, an improvement of breastfeeding practices seems to be more effective and safer than the use of an off-label domperidone treatment.
Topics: Breast Feeding; Domperidone; Female; Galactogogues; Humans; Infant, Newborn; Milk, Human; Risk Assessment
PubMed: 25475074
DOI: 10.1177/0890334414561265 -
Journal of Clinical Medicine Sep 2022The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are... (Review)
Review
Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO's International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.
PubMed: 36142915
DOI: 10.3390/jcm11185268 -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
Children (Basel, Switzerland) Nov 2022QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However,... (Review)
Review
QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, the interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neonates. Further research in this age category is needed to improve primary screening practices and QTcthresholds, earlier detection of risk factors and precision pharmacovigilance.
PubMed: 36421220
DOI: 10.3390/children9111771 -
BMJ Clinical Evidence Oct 2008Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with... (Review)
Review
INTRODUCTION
Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with regurgitation, and frequent back arching. A cross-sectional survey of parents of 948 infants attending 19 primary care paediatric practices found that regurgitation of at least one episode a day was reported in 51% of infants aged 0-3 months.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: domperidone, feed thickeners in infants, H(2) antagonists, head elevated sleep positioning, left lateral or prone sleep positioning, metoclopramide, proton pump inhibitors, sodium alginate, surgery, soy formula with added fibre, and weight loss.
Topics: Acute Disease; Administration, Oral; Child; Cross-Sectional Studies; Domperidone; Gastroesophageal Reflux; Humans; Incidence; Infant; Metoclopramide; Proton Pump Inhibitors
PubMed: 19445794
DOI: No ID Found -
Clinical Gastroenterology and... Jul 2008Despite being widely used in more than 20 countries for the treatment of diabetic gastroparesis for several decades, domperidone is approved only on an investigational... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Despite being widely used in more than 20 countries for the treatment of diabetic gastroparesis for several decades, domperidone is approved only on an investigational basis in the United States. However, because its use is increasing, it is important for gastroenterologists in this country to understand its effectiveness in this condition. The literature on this subject varies considerably with respect to the methods and outcome measures, making a meta-analysis unfeasible.
METHODS
Our objective was to systematically analyze studies of the efficacy of domperidone in diabetic gastroparesis, with a focus on their methodologic and scientific merit. Information from 28 trials (11 full articles and 17 abstracts) from 1981 to 2007 was analyzed.
RESULTS
The average study quality score was 8.3 out of a possible 15 and the total sample size equaled 1016. Overall, 64% of the studies showed significant efficacy of domperidone on the improvement of symptoms. Sixty percent of the studies showed an efficacy in gastric emptying and 67% of the studies proved the drug effective in reducing hospital admissions.
CONCLUSIONS
Overall, our assessment is that there is level 3 evidence for the efficacy of domperidone in diabetic gastroparesis, leading to a grade C recommendation for its use in this condition. These results need to be interpreted very cautiously because of significant methodologic limitations of these studies, including the fact that most positive studies lacked a control arm. It is clear that larger and better-designed studies are needed to further validate the use of this drug in diabetic gastroparesis.
Topics: Clinical Trials as Topic; Diabetes Complications; Domperidone; Gastroparesis; Humans; Treatment Outcome; United States
PubMed: 18524689
DOI: 10.1016/j.cgh.2008.02.065 -
Farmacia Hospitalaria : Organo Oficial... Sep 2014To assess the association of the use of domperidone in infants with QTc interval prolongation and proarrhythmic events. (Review)
Review
AIMS
To assess the association of the use of domperidone in infants with QTc interval prolongation and proarrhythmic events.
METHODS
A systematic search of the scientific literature was conducted without any date or language restriction. The electronic database MEDLINE and the sources LILACS, ScIELO and Cochrane library were consulted.
RESULTS
From the twelve identified studies, eight were excluded because they did not meet the inclusion criteria. One case report and three pilot studies were selected. Rocha et al (2005) reported the case of an infant (age 3 months) with QTc interval = 463 ms after being treated during one month with 1.8 mg/kg/day of oral domperidone. Djeddi et al (2008) administered an average dose of 1.3 mg/kg/day to 31 neonates; QTc interval prolongation > 30 ms was observed in nine neonates. Hegar et al (2009) studied 10 infants (mean age 5.6 months) who received 0.8 mg/ kg/day of oral domperidone; QTc interval prolongation was not observed. Günlemez et al (2010) enrolled 40 premature infants who were administered 1 mg/kg/day of oral domperidone; the QTc interval increased to above 450 ms in two infants.
CONCLUSIONS
Although evidence that orally administrated domperidone in infants produces prolongation of QTc interval was found, further studies are needed in order to quantify the risk associated with the drug in that population. We suggest that heath professionals should conduct ECGs to infants treated with domperidone and inform the pharmacovigilance system the occurrence of any case of adverse event.
Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cisapride; Contraindications; Cytochrome P-450 CYP3A; Domperidone; Dopamine Antagonists; Drug Interactions; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Long QT Syndrome; Pilot Projects; Prospective Studies
PubMed: 25344138
DOI: 10.7399/fh.2014.38.5.7957 -
Wiener Medizinische Wochenschrift (1946) May 2017The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe... (Comparative Study)
Comparative Study Review
Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.
The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.
Topics: Domperidone; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Metoclopramide; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic
PubMed: 28424994
DOI: 10.1007/s10354-017-0557-3 -
BJOG : An International Journal of... Oct 2018Mothers of preterm infants often struggle to produce enough breast milk to meet the nutritional needs of their infant. Galactagogues such as domperidone are often... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mothers of preterm infants often struggle to produce enough breast milk to meet the nutritional needs of their infant. Galactagogues such as domperidone are often prescribed to increase breast milk supply but evidence supporting their role in clinical practice is uncertain.
OBJECTIVE
To evaluate the efficacy and safety of domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants.
SEARCH STRATEGY
MEDLINE, Embase and Web of Science were searched without language restrictions from first publication until January 2017. Bibliographies of articles and reviews were hand-searched for additional reports.
SELECTION CRITERIA
Randomised controlled trials that compared domperidone with placebo in mothers of preterm infants (<37 weeks' gestation) experiencing insufficient milk supply.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data and evaluated study quality. Differences in breast milk volume and adverse events were combined using fixed effects meta-analysis.
MAIN RESULTS
The pooled analysis of five trials consisting of 194 women demonstrated a moderate increase in daily breast milk volume of 88.3 ml/day (95% CI 56.8-119.8) with the use of domperidone compared with placebo. No difference was evident with respect to maternal adverse events (odds ratio 1.05, 95% CI 0.65-1.71), with no reported cases of prolonged QTc syndrome or sudden cardiac death. Sensitivity analyses showed no important differences in the estimates of effects.
CONCLUSIONS
Domperidone is well tolerated and results in a moderate short-term increase in expressed breast milk volume among mothers of preterm infants previously identified as having insufficient breast milk supply.
TWEETABLE ABSTRACT
Domperidone leads to short-term improvements in breast milk volume in mothers of preterm infants.
Topics: Adult; Breast Milk Expression; Domperidone; Female; Humans; Infant, Newborn; Infant, Premature; Lactation; Milk, Human; Treatment Outcome
PubMed: 29469929
DOI: 10.1111/1471-0528.15177 -
The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2