Domperidone-associated sudden cardiac death in the general population and implications for use in patients undergoing hemodialysis: a literature review.

BACKGROUND Domperidone, an effective prokinetic agent, is commonly used to manage symptoms of gastroparesis. Health regulatory agencies have issued warnings about an increased risk of sudden cardiac death associated with use of this drug. OBJECTIVE To evaluate the evidence for domperidone-associated sudden cardiac death and to determine whether this drug can be safely used for gastroparesis in patients undergoing dialysis. DATA SOURCES Two databases (MEDLINE [1965 to September 2014] and Embase [1980 to September 2014]) were searched using the Medical Subject Headings "domperidone", "sudden cardiac death", and "cardiac arrhythmia". The search was limited to studies conducted in humans and published in English. Advisories from health regulatory agencies (Health Canada, the European Medicines Agency, and the US Food and Drug Administration) were identified and reviewed. STUDY SELECTION Studies eligible for inclusion in this narrative review were randomized controlled trials and cohort, case-control, cross-sectional, and other epidemiological studies comparing use and non-use of domperidone for the outcome of sudden cardiac death in adults. Abstracts of eligible case reports and case series were also included. DATA SYNTHESIS Despite inconsistencies in their decisions, the various drug regulatory authorities have acknowledged the potential safety concern of increased risk of sudden cardiac death associated with domperidone. To date, no randomized controlled studies have shown an increased risk of this outcome secondary to domperidone use. Current regulatory recommendations and approval decisions are based on 2 large observational epidemiological studies that generated a signal of increased risk. The strengths and limitations of these studies were evaluated in detail. No direct evidence applicable to patients with end-stage renal disease was found. In vitro evidence suggests that the risk of sudden cardiac death is dose-related. CONCLUSIONS Given gaps in the literature, use of domperidone for patients undergoing dialysis should be assessed on a case-by-case basis. Extreme caution should be used for patients taking more than 30 mg/day of this drug.