Domperidone

[Canadian Boxed Warning]: Domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death, particularly with doses >30 mg or when used in patients >60 years of age. Use the lowest possible dose for the shortest duration necessary. Do not exceed 30 mg/day. Avoid use of domperidone for the following: concomitant use of drugs which prolong the QTc interval and with potent CYP3A4 inhibitors which may increase domperidone exposure, existing prolongation of cardiac conduction intervals (particularly QT), significant electrolyte disturbances or underlying cardiac diseases (eg, heart failure). QTc prolongation, life-threatening tachyarrhythmias (eg, torsade de pointes), and cardiac arrest have been reported after use; these adverse effects may be precipitated in patients with preexisting prolonged cardiac conduction or other underlying cardiac disease, hypokalemia, or receiving other QTc-prolonging agents. The American College of Gastroenterology guidelines recommend baseline and follow-up ECGs and avoiding use if corrected QT is >450 msec in male patients or >470 msec in female patients (Arnold 2013; Camilleri 2013).

May increase prolactin levels (dose-dependent response); may be asymptomatic (clinical consequence of chronically-elevated prolactin is unknown) or may present symptomatically as galactorrhea, gynecomastia, amenorrhea, or impotence (reversible upon decreasing dose or discontinuing drug). Use is contraindicated in patients with prolactinomas. Disease-related concerns:

Use caution when administering to patients with a personal or family history of breast cancer; evidence regarding an association between chronic use of dopamine-receptor antagonists and breast cancer is limited and nonconclusive.

Undergoes extensive hepatic metabolism; use is contraindicated in patients with moderate to severe hepatic impairment; use with caution in mild impairment.

Use with caution in patients with severe renal impairment; dosage and/or frequency of administration may need adjusted with repeated use and/or long-term therapy. Monitor renal function regularly, particularly with long-term therapy. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

In 2004, the Food and Drug Administration (FDA) issued a warning recommending that domperidone not be used off-label to increase milk production in breast-feeding women due to safety concerns. Several cases of cardiac arrhythmia, cardiac arrest, and sudden death have been reported in patients receiving intravenous domperidone. The risk of similar adverse events in breast-feeding women is unknown. Domperidone is not available for any use in the United States (except via severe GI disorder IND) and does not have approval for this indication in other countries.