domperidone

Therapeutic Area:

,

Generic Name:

domperidone

Dosage Form:

tablet

Drug Dose

Therapeutic Indications:

GI motility disorders: Symptomatic management of upper GI motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis

 Nausea/vomiting associated with dopamine-agonist anti-Parkinson agents: Prevention of GI symptoms (eg, nausea, vomiting) associated with use of dopamine-agonist anti-Parkinson agents

Mechanism of Action:

Domperidone has peripheral dopamine receptor blocking properties and does not readily cross the blood-brain barrier. It increases esophageal peristalsis and increases lower esophageal sphincter pressure, increases gastric motility and peristalsis, and enhances gastroduodenal coordination, therefore, facilitating gastric emptying and decreasing small bowel transit time.

Method of Administration:

10 mg 3 times daily (maximum: 30 mg/day). Use the lowest effective dose for the shortest duration necessary. For gastroparesis, the American College of Gastroenterology recommends initiating at 10 mg 3 times daily

Notes

Contraindications:

Hypersensitivity to domperidone or any component of the formulation; prolactin releasing pituitary tumor (prolactinoma); known existing prolongation of cardiac conduction intervals, particularly QT; significant electrolyte disturbances; underlying cardiac disease (eg, heart failure); moderate or severe hepatic impairment; patients with GI hemorrhage, mechanical obstruction, or perforation; concomitant use with potent CYP3A4 inhibitors such as azole antifungals (eg, ketoconazole), macrolides (eg, erythromycin), protease inhibitors, or nefazodone; concomitant use with QT-prolonging drugs

Interactions:

Anticholinergic Agents: May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Haloperidol: May enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Ondansetron: Domperidone may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Domperidone may enhance the QTcprolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combination

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Domperidone. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combination

Pregnancy and Lactation:

An increased risk of adverse fetal events has not been observed following maternal use of domperidone in the first trimester.

Breastfeeding is not recommended.

Warning and Precaution:

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.

  • Elevated prolactin levels: 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.

Adverse Reactions:

Central nervous system: Headache (≤1%), migraine (≤1%)

Gastrointestinal: Xerostomia (2%)

Storage:

Store below 30ºC and protect from light and moisture.