Formulary forum - Domperidone: A peripherally acting dopamine(2)-receptor antagonist

OBJECTIVE: TO review the pharmacology, pharmacokinetics, efficacy, and safe ty of domperidone in the treatment of gastrointestinal motility disorders a nd emesis. DATA SOURCES: MEDLINE and Excerpta Medica online databases were searched to identify published reports. STUDY SELECTION: Domperidone has been marketed worldwide outside the US sin ce 1978, and extensive clinical data for this drug are available. This revi ew focuses on the clinical experience from controlled studies of domperidon e in the treatment of motility disorders, particularly diabetic gastropares is. Also, case reports are used in summarizing safety. The control comparat or groups included placebo or other prokinetic drugs (metoclopramide and ci sapride). Controlled clinical trials of domperidone's efficacy and safety a s an antiemetic are also briefly examined. Although a variety of domperidon e dosage forms have been marketed, data generated from trials using the 10- mg tablet are highlighted because this is the only dosage form available in Canada and is under investigation in the US. DATA EXTRACTION: Because symptoms do not correlate with objective measures of gastrointestinal motility and they are the primary reason that patients with motility disorders seek treatment, the primary outcome extracted from the clinical studies was symptomatic response to treatment. Safety and effi cacy between domperidone and placebo, metoclopramide, or cisapride were com pared. DATA SYNTHESIS: Domperidone, a peripheral dopamine(2)-receptor antagonist, regulates the motility of gastric and small intestinal smooth muscle and ha s been shown to have some effects on the motor function of the esophagus. I t also has antiemetic activity as a result of blockade of dopamine receptor s in the chemoreceptor trigger zone. In controlled clinical trials, domperi done provided better relief of symptoms (anorexia, nausea, vomiting, abdomi nal pain, early satiety, bloating, distension) than placebo in patients wit h symptoms of diabetic gastropathy; symptomatic improvement was similar wit h domperidone and metoclopramide or cisapride. Domperidone also provided sh ort-term relief of symptoms in patients with dyspepsia or gastroesophageal reflux, prevented nausea and vomiting associated with emetogenic chemothera py, and prevented the gastrointestinal and emetic adverse effects of antipa rkinsonian drugs. Because very little domperidone crosses the blood-brain b arrier, reports of central nervous system adverse effects, such as dystonic reactions, are rare. CONCLUSIONS: Domperidone is a unique gastrokinetic and antiemetic drug. Bec ause of its favorable safety profile, domperidone appears to be an attracti ve alternative to metoclopramide. In the management of diabetic gastropathy , domperidone's antiemetic activity distinguishes it from cisapride.