Domperidone - Drug Monograph

Introduction

Domperidone is a dopamine D₂ and D₃ receptor antagonist with prokinetic and antiemetic properties. It is structurally related to butyrophenones and benzimidazoles and is primarily used for the management of gastrointestinal motility disorders and nausea/vomiting. Unlike metoclopramide, domperidone does not readily cross the blood-brain barrier, resulting in fewer central nervous system side effects.

Mechanism of Action

Domperidone acts as a selective peripheral dopamine D₂ and D₃ receptor antagonist. By blocking dopamine receptors in the chemoreceptor trigger zone (CTZ) and gastrointestinal tract, it:

• Increases lower esophageal sphincter pressure
• Enhances gastric emptying
• Improves gastroduodenal coordination
• Exerts antiemetic effects through CTZ inhibition

The drug does not significantly affect cholinergic or serotonin receptors.

Indications

• Symptomatic treatment of nausea and vomiting

• Gastroparesis (particularly diabetic gastroparesis)
• Gastroesophageal reflux disease (GERD)
• Functional dyspepsia
• Stimulation of lactation (galactagogue use)
• Parkinson's disease-associated gastrointestinal symptoms

Dosage and Administration

• Nausea/vomiting: 10-20 mg orally 3-4 times daily (maximum 80 mg/day)
• Gastroparesis: 10-20 mg orally 30 minutes before meals and at bedtime

• Renal impairment: Reduce dose or increase dosing interval
• Hepatic impairment: Use with caution; consider dose reduction
• Elderly: Start with lower doses due to increased susceptibility to adverse effects
• Pediatrics: Not recommended for children under 12 years (varies by jurisdiction)

Pharmacokinetics

Contraindications

• Known hypersensitivity to domperidone
• Prolactin-releasing pituitary tumor (prolactinoma)
• Conditions where cardiac conduction is or could be impaired
• Significant electrolyte disturbances
• Moderate to severe hepatic impairment
• Concomitant use with potent CYP3A4 inhibitors
• History of ventricular arrhythmia or QT prolongation

Warnings and Precautions

• Use lowest effective dose for shortest duration
• Avoid in patients with existing QT prolongation
• Monitor for signs of arrhythmia
• Consider ECG monitoring in high-risk patients
• Use with caution in patients with cardiac disease
• Discontinue if symptoms of cardiac arrhythmia occur

• Hyperprolactinemia risk
• Neurologic adverse effects (although less common than with metoclopramide)
• Electrolyte monitoring recommended
• Not recommended during pregnancy unless clearly needed

Drug Interactions

• CYP3A4 inhibitors: Ketoconazole, itraconazole, clarithromycin, ritonavir (contraindicated)
• QT-prolonging drugs: Amiodarone, procainamide, quinidine, certain antidepressants
• Dopaminergic agents: May reduce efficacy of levodopa and dopamine agonists

• Anticholinergic drugs: May reduce domperidone's effects
• CYP3A4 inducers: Rifampin, carbamazepine (may reduce domperidone levels)

Adverse Effects

• Headache
• Dry mouth
• Abdominal cramps
• Diarrhea
• Increased prolactin levels

• QT prolongation and torsades de pointes
• Ventricular arrhythmias
• Sudden cardiac death
• Hyperprolactinemia (galactorrhea, gynecomastia)
• Extrapyramidal symptoms (rare)
• Anaphylactic reactions

Monitoring Parameters

• Cardiac: ECG monitoring (especially in high-risk patients), signs/symptoms of arrhythmia
• Electrolytes: Potassium, magnesium (particularly during prolonged use)
• Prolactin levels: If symptoms of hyperprolactinemia occur
• Efficacy: Symptom improvement, reduction in nausea/vomiting
• Neurologic: Monitoring for extrapyramidal symptoms
• Renal/hepatic function: Periodic assessment in patients with impairment

Patient Education

• Take medication 15-30 minutes before meals for gastrointestinal indications
• Report any palpitations, dizziness, or fainting immediately
• Be aware of potential dry mouth and maintain adequate hydration
• Do not exceed prescribed dosage
• Inform healthcare providers of all medications being taken
• Seek immediate medical attention for chest pain or irregular heartbeat
• Be aware that breastfeeding benefits should be weighed against potential risks
• Report any unusual muscle movements or restlessness

References

1. FDA. (2004). Domperidone prescribing information 2. Reddymasu SC, et al. (2007). Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 3. Ehrenpreis ED, et al. (2014). Domperidone for gastroparesis: systematic review and meta-analysis. Neurogastroenterol Motil 4. van Noord C, et al. (2010). Domperidone and ventricular arrhythmia or sudden cardiac death: population based cohort study. BMJ 5. World Health Organization. (2002). Domperidone in the WHO Model List of Essential Medicines 6. Liu Y, et al. (2019). Cardiac safety of domperidone: a systematic review and meta-analysis. Clin Pharmacol Ther 7. Pharmaceutical Benefits Advisory Committee. (2015). Domperidone: safety advisory