Domperidone

 

Comprehensive Clinical Overview of Domperidone

Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist. It exerts its prokinetic and antiemetic effects predominantly by blocking dopamine receptors in the gastrointestinal (GI) tract and the chemoreceptor trigger zone (CTZ), which lies outside the blood–brain barrier. This unique property greatly reduces the likelihood of central nervous system (CNS) side effects such as sedation and extrapyramidal symptoms.

Clinically, Domperidone is commonly used to manage GI motility disorders and alleviate nausea and vomiting. It enhances coordinated gastric contractions, accelerates gastric emptying, and improves patient tolerance to feeding, particularly in disorders like gastroparesis.

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Clinical Indications

Domperidone is indicated for the treatment of:

• Nausea and vomiting induced by chemotherapy, radiotherapy, migraines, or dopaminergic medications

• Gastroparesis, especially in diabetic patients

• Gastro-oesophageal reflux disease (GERD) and functional dyspepsia

• Off-label: Lactation enhancement via increased prolactin secretion

Its favourable safety profile, especially when compared with centrally acting antiemetics such as metoclopramide, makes it the preferred agent in several clinical situations.

Dosage and Administration

• Adults: 10 mg orally, 15–30 minutes before meals, up to three times daily. Maximum recommended dose: 30 mg/day.

• Paediatrics: 0.25–0.5 mg/kg per dose, up to three times daily. Specialist supervision is required due to cardiac risk.

For acute indications, treatment should not exceed seven days. Long-term use should involve periodic clinical reviews and cardiac monitoring.

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Dose Adjustments in Special Populations

Renal Impairment

In moderate to severe renal dysfunction, Domperidone clearance is reduced. While the individual dose may remain unchanged, the dosing interval should be extended. Routine monitoring of renal function and ECGs is advised for prolonged therapy.

Hepatic Impairment

As Domperidone is extensively metabolised by hepatic CYP3A4 enzymes, it is contraindicated in patients with moderate to severe hepatic impairment. In mild hepatic dysfunction, use with caution and monitor liver enzymes regularly.

Pregnancy and Lactation

Domperidone should be used in pregnancy only if the potential benefits justify the potential risks. In breastfeeding women, Domperidone may increase prolactin levels and enhance milk production. However, due to limited long-term safety data in infants, clinical supervision is advised.

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Adverse Effects

Common Adverse Effects

• Dry mouth

• Abdominal cramps

• Headache

• Dizziness

Serious or Less Common Adverse Effects

• QT interval prolongation

• Cardiac arrhythmias

• Galactorrhoea

• Menstrual irregularities

• Rare extrapyramidal reactions

Patients with pre-existing cardiac conditions should undergo ECG screening prior to treatment initiation.

Drug Combinations and Infusion Considerations

Domperidone is often co-prescribed with proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids for comprehensive management of reflux and dyspepsia. Though oral administration is standard, parenteral use has been explored off-label in some regions.

Precautions During Infusion (Off-Label Use)

• Use dedicated IV lines to avoid drug incompatibility

• Infuse slowly under ECG monitoring

• Avoid simultaneous infusion with QT-prolonging medications

Formulations and Dosages

Formulation	Strength	Route
Tablet	10 mg, 20 mg	Oral
Oral Suspension	1 mg/mL, 5 mg/5 mL	Oral
Suppository	30 mg	Rectal
Injectable (rare)	10 mg/2 mL	IV/IM

Pharmacology

Mechanism of Action

Domperidone antagonises peripheral dopamine receptors in the upper GI tract and CTZ. This results in increased gastric motility and suppression of nausea.

Pharmacokinetics

• Absorption: Rapid but incomplete due to significant first-pass metabolism

• Bioavailability: 10–15%

• Protein Binding: ~93%

• Metabolism: Hepatic via CYP3A4

• Excretion: Faeces (66%), urine (33%)

• Half-life: Approximately 7–9 hours

Antibacterial Activity

Domperidone has no direct antimicrobial effects. However, it may be used in symptomatic management alongside antibiotics in gastrointestinal infections.

Drug Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Significantly increase Domperidone plasma concentrations, raising cardiac risk.

• QT-prolonging drugs (e.g., amiodarone, sotalol): Co-administration may exacerbate QT prolongation.

• Antacids and H2 blockers: Can reduce Domperidone’s bioavailability; spacing administration is recommended.

Comparison with Other Prokinetic Agents

Drug	Mechanism	CNS Effects	QT Risk	Use in Lactation
Domperidone	Peripheral D2 antagonist	Minimal	Moderate	Off-label; supervised
Metoclopramide	Central D2 antagonist	High	Moderate	Use with caution
Erythromycin	Motilin receptor agonist	None	Moderate	Generally considered safe
Cisapride	5-HT4 receptor agonist	None	High	Contraindicated
Prucalopride	Selective 5-HT4 receptor agonist	Minimal	Low	Limited safety data

Clinical Precautions

• Contraindicated in patients with known QT prolongation, severe hepatic disease, or established cardiac arrhythmias

• Use with caution in elderly patients

• Comprehensive drug interaction screening is vital

• Monitor ECGs in long-term or polypharmacy scenarios

Toxicology and Overdose

Clinical Presentation

• Drowsiness

• Confusion

• Extrapyramidal symptoms

• Cardiac arrhythmias

Management of Overdose

• Immediate cessation of Domperidone

• Activated charcoal may be considered if overdose is recent

• Symptomatic management, particularly for arrhythmias and dystonia

• Continuous ECG monitoring

• No specific antidote; benzodiazepines may be used to manage extrapyramidal effects

Recent Updates (2025)

The European Medicines Agency (EMA) reasserted the importance of limited treatment duration and conservative dosing. NICE reiterated the necessity of ECG screening, especially in patients taking CYP3A4 inhibitors. New advancements include wearable ECG monitoring technologies to enhance outpatient safety.

Summary Points

• Domperidone is a peripheral dopamine antagonist with strong prokinetic and antiemetic effects

• Indicated for nausea, vomiting, gastroparesis, and reflux-related conditions

• Use cautiously in patients with cardiac or hepatic impairments

• Avoid prolonged use beyond seven days without proper monitoring

• Regular ECGs and interaction screening improve safety

References

1. European Medicines Agency (2025). Domperidone Safety Update.

2. British National Formulary (BNF), 2025.

3. NICE Guidelines on Gastrointestinal Disorders, 2025.

4. Martindale: The Complete Drug Reference, 2025.

5. WHO Essential Medicines List, 2024.

6. UK MHRA Drug Safety Bulletin, 2025.

7. UCL Clinical Pharmacology Lecture Notes, 2025.

8. Cochrane Library, "Domperidone and Lactation", 2024.

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