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Journal of Pediatric Gastroenterology... Aug 2023Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper... (Review)
Review
Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication ("off label") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an "off label/on evidence" prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.
Topics: Infant; Humans; Child; Domperidone; Antiemetics; Gastrointestinal Diseases; Gastrointestinal Agents; Vomiting
PubMed: 37159421
DOI: 10.1097/MPG.0000000000003822 -
The American Journal of Gastroenterology Sep 2007Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function... (Review)
Review
Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Unlike metoclopramide, it does not cause any adverse neurological symptoms as it has minimal penetration through the blood-brain barrier. It thus provides an excellent safety profile for long-term administration orally in the recommended doses. Domperidone is widely used in many countries and can now be officially prescribed to patients in the United States by an investigational new drug application for the treatment of gastroparesis and any condition causing chronic nausea and vomiting. In view of this additional clinical exposure of domperidone to a new generation of gastroenterologists and other specialists, the purpose of this timely review is to revisit the pharmacology, clinical application, and safety profile of this beneficial medication.
Topics: Antiemetics; Domperidone; Dopamine Antagonists; Gastrointestinal Diseases; Humans; Nausea; Vomiting
PubMed: 17488253
DOI: 10.1111/j.1572-0241.2007.01255.x -
Indian Pediatrics Sep 1989
Review
Topics: Child; Child, Preschool; Domperidone; Gastric Emptying; Humans; Nausea; Vomiting
PubMed: 2699318
DOI: No ID Found -
General Pharmacology 1988
Review
Topics: Colonic Diseases, Functional; Domperidone; Dyspepsia; Esophagitis, Peptic; Gastrointestinal Motility; Humans; Nausea; Parkinson Disease; Vomiting
PubMed: 3044918
DOI: 10.1016/0306-3623(88)90153-x -
Breastfeeding Medicine : the Official... Jun 2017
Review
Topics: Breast Feeding; Domperidone; Female; Humans; Lactation; Patient Safety; Practice Guidelines as Topic; United States; United States Food and Drug Administration
PubMed: 28440671
DOI: 10.1089/bfm.2017.0043 -
Journal of Cardiovascular Pharmacology Mar 2013Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization... (Review)
Review
BACKGROUND
Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism.
METHODS AND RESULTS
Experiments were executed in isolated female rabbit hearts perfused for 150 minutes with domperidone 30, 60, or 100 nM. Domperidone significantly prolonged the action potential duration: +9% at 30 nM, +32% at 60 nM, and +48% at 100 nM. Domperidone induced significant disturbances of repolarization in 83% of hearts at 60 nM and in 100% at 100 nM, including early afterdepolarizations and polymorphic ventricular tachycardia. Maximum therapeutic free drug plasma concentration of domperidone (19 nM) yields a safety index of only ∼2.5, that is, 12-fold below the accepted minimum. Gastrointestinal benefits and risks for SCD were derived from the literature. The defined daily dose of domperidone (30 mg/day) fails to show unequivocal gastrointestinal benefits beyond a placebo effect. In contrast, 5 of 5 population-based studies show that oral domperidone significantly increases the odds ratio for SCD to 2.8 (1.53-6.21) and it increases sharply above 30 mg/day.
CONCLUSIONS
Because domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine.
Topics: Action Potentials; Animals; Antiemetics; Death, Sudden, Cardiac; Domperidone; Dopamine Antagonists; Dyspepsia; Electrocardiography; Female; Gastroesophageal Reflux; Gastrointestinal Tract; Heart; Humans; In Vitro Techniques; Male; Osmolar Concentration; Perfusion; Rabbits; Reproducibility of Results; Risk Assessment; Severity of Illness Index; Tachycardia, Ventricular
PubMed: 23188128
DOI: 10.1097/FJC.0b013e31827afd0d -
Clinical Neuropharmacology 1986
Review
Topics: Antiparkinson Agents; Domperidone; Drug Therapy, Combination; Humans; Parkinson Disease
PubMed: 3542205
DOI: 10.1097/00002826-198612000-00003 -
Drugs Sep 1998Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with gastroprokinetic and antiemetic properties. It increases the frequency and duration of... (Review)
Review
UNLABELLED
Domperidone is a selective antagonist at peripheral dopamine D2 receptors, with gastroprokinetic and antiemetic properties. It increases the frequency and duration of antral and duodenal contractions, thus decreasing/improving transit time of food through the gastrointestinal tract. Gastric emptying of liquids and solids is significantly improved with oral domperidone 40 to 120 mg/day in patients with diabetic gastropathy. Oral domperidone 40 to 80 mg/day significantly decreased the severity of symptoms of gastropathy from baseline values in 66 to 88% of patients with type 1 (insulin-dependent) or insulin-requiring diabetes mellitus. Double-blind withdrawal of domperidone from patients who had responded previously led to greater deterioration of symptoms in patients with delayed gastric emptying than in those who continued receiving the drug. Quality of life was significantly improved in patients who showed a symptomatic response to domperidone. The administration of domperidone 40 to 120 mg/day significantly reduced hospitalisation rates in patients with gastropathy. The symptomatic improvement with domperidone 80 mg/day was similar to that seen with cisapride 40 mg/day or metoclopramide 40 mg/day, and therapeutic benefits seen in symptoms of gastropathy were maintained with domperidone for up to 12 years. Domperidone 40 to 80 mg/day may be effective in patients who are refractory to metoclopramide, and a combination of domperidone 80 mg/day with cisapride 80 mg/day may improve some symptoms in patients who do not respond to either agent alone. Domperidone 40 to 120 mg/day was well tolerated for periods up to 12 years in trials in patients with diabetic gastropathy. Adverse events with domperidone 80 mg/day were similar to those seen in placebo recipients and significantly fewer than in patients receiving metoclopramide 40 mg/day. Although significant elevation of plasma prolactin levels (unrelated to dosage and duration of treatment) occurred in all domperidone recipients, prolactin-related adverse events were observed in only 10 to 20% of patients.
CONCLUSIONS
The available data suggest that domperidone 40 to 80 mg/day is an effective agent for the management of symptoms of gastropathy in patients with type 1 diabetes mellitus. In addition, it may provide symptom improvement in patients with gastropathy refractory to other gastroprokinetic agents. Domperidone maintains efficacy in the long term (up to 12 years) and appears to have a better tolerability profile than metoclopramide 40 mg/day.
Topics: Animals; Diabetes Complications; Diabetes Mellitus, Experimental; Domperidone; Dopamine Antagonists; Humans; Stomach Diseases
PubMed: 9777316
DOI: 10.2165/00003495-199856030-00011 -
International Journal of Pharmaceutical... 2014Domperidone is a prokinetic agent used as a second-line treatment option for gastroparesis in those unable to tolerate metoclopramide. Via inhibition of dopamine-2... (Review)
Review
Domperidone is a prokinetic agent used as a second-line treatment option for gastroparesis in those unable to tolerate metoclopramide. Via inhibition of dopamine-2 receptors within the gastrointestinal tract and various parts of the central and peripheral nervous system, domperidone helps to facilitate peristalsis and gastric emptying. A major side effect of domperidone is prolactinemia, allowing it to be used off-label for the purpose of inducing lactation. In the U.S., domperidone is currently not U.S. Food and Drug Administration approved due to various case reports and literature associating the risks of sudden cardiac death and ventricular arrhythmia with the use of domperidone. Despite the evidence against the use of domperidone, it is still being widely used in Canada and Europe for both gastroparesis and to induce milk let-down. This article is a literature review intending to assess the risks associated with the use of domperidone in gastroparesis and lactation.
Topics: Domperidone; Dopamine Antagonists; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Lactation; Male; Patient Safety; Pregnancy; Risk Assessment; Risk Factors
PubMed: 25306766
DOI: No ID Found -
CMAJ : Canadian Medical Association... Sep 1986Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not... (Clinical Trial)
Clinical Trial Review
Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not readily enter the central nervous system. Domperidone acts as both an antiemetic and an upper gastrointestinal tract prokinetic agent. It is rapidly absorbed after oral administration, and few side effects have been reported. Domperidone has been approved for use in Canada for the symptomatic management of upper gastrointestinal tract motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist agents in Parkinson's disease. The pharmacologic features, indications and side effects of domperidone are reviewed.
Topics: Administration, Oral; Adult; Child; Clinical Trials as Topic; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Motility; Headache; Humans; Infant; Migraine Disorders; Nausea; Parkinson Disease; Stomach Diseases; Tablets; Vomiting
PubMed: 3527396
DOI: No ID Found