Effect of Chronic Domperidone Use on QT Interval

Abstract

Goals: The goal of this study was to determine the effect and safety of domperidone on QTc interval at the commonly prescribed doses of 30 to 80 mg daily. Background: Domperidone is a dopamine receptor antagonist used for the treatment of gastroparesis. However, it has been associated with QT prolongation, ventricular arrhythmias, and sudden cardiac death. Study: This study analyzed patients prescribed domperidone for treatment of gastroparesis between January 2012 and September 2017 at a single center. This study reviewed EKGs, primarily the QTc interval, taken at baseline, 2 to 6 months after initiation of domperidone, 6 to 12 months after initiation, and ≥12 months after initiation. Concurrent QTc prolonging medications were recorded for each patient. The primary endpoint was QTc prolongation >500 ms. Secondary endpoints were QTc >450 ms for males, a QTc>470 ms for females, QTc prolongation ≥20 ms above baseline, and QTc prolongation >60 ms above baseline. Results: In total, 246 patients were included for analysis (age, 46.3±17.4 y; F 209). EKGs were available for all 246 patients before treatment, 170 patients at 2 to 6 months, 135 at 6 to 12 months, and 152 patients at least 1 year after domperidone initiation. Of 246 subjects, 15 patients (6.1%, 9 female) had clinically important QTc prolongation; 11 had QTc >450 ms for males or >470 ms for females; none had QTc prolongation >500 ms; 5 (2.0%) had >60 ms over baseline and 61 (24.7%) patients had QTc increase of ≥20 ms but <60 ms from baseline. Conclusions: Domperidone at the conventionally used doses to treat gastroparesis (30 to 80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant. These data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis.

Risk of domperidone induced severe ventricular arrhythmia

“…However, of late, given that several case reports and retrospective studies have reported an association between domperidone and severe VA, its use has been strictly restricted. Although some meta-analyses indicate that domperidone may not be associated with the risk of overall cardiovascular (CV) events and QT prolongation [15][16][17] , many clinicians hesitate to prescribe it to their patients. Thus, it is essential to conduct welldesigned studies to clarify the association between domperidone and severe VA. We conducted a self-controlled case series based on a large population cohort, which could enable the adjustment of all fixed time-independent confounders during the observation period.…”

Pharmacologic treatment of GERD: Where we are now, and where are we going?

“…However, for patients with an underlying QT susceptibility, caution should be used. 192 Other agents with a prokinetic effect, such as acotiamide, are still under investigation and have not yet been proven effective. Evidence is limited because early studies had poor enrollment and remain incomplete.…”

“…Despite the well‐known cardiac risk of domperidone, studies of real‐life use reported a very limited QT effect at low daily doses. However, for patients with an underlying QT susceptibility, caution should be used 192 …”

Practical management approach to gastroparesis

“…26 Prospective clinical trials have not found similar effects. 20,22,27,28 Routine follow up with regular electrocardiogram is recommended. 22 Rotation from domperidone to another prokinetic agent has been suggested if a corrected QT interval of greater than 470 ms in males and 450 ms in females has been demonstrated.…”