Domperidone

Domperidone is a peripherally selective dopamine D₂ and D₃ receptor antagonist used primarily as an antiemetic (anti-nausea) and prokinetic agent to stimulate gastrointestinal motility. Its pharmacological action is based on blocking dopamine receptors in the gut and at the chemoreceptor trigger zone (CTZ), located outside the blood–brain barrier, which allows it to reduce nausea and vomiting without central nervous system effects like sedation or extrapyramidal symptoms—unless taken at very high doses or in infants.

Its use has become restricted in many countries due to concerns about QT interval prolongation and serious cardiac arrhythmias, especially in older adults and in combination with CYP3A4 inhibitors.

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Pharmacological Classification

• Therapeutic class: Antiemetic / Gastroprokinetic

• Pharmacologic class: Dopamine D₂ and D₃ receptor antagonist

• ATC code: A03FA03

• Legal classification: Prescription-only in most countries; dose and duration-restricted

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Chemical and Formulation Information

• Generic name: Domperidone

• Common brand names: Motilium®, Domstal®, Vometa®, Peridys®

• Formulations:

  • Oral tablets (10 mg)

  • Oral suspension (1 mg/mL or 5 mg/5 mL)

  • Orally disintegrating tablets

  • Rectal suppositories (not widely used)

Domperidone does not cross the blood–brain barrier easily, differentiating it from centrally acting dopamine antagonists like metoclopramide or prochlorperazine.

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Mechanism of Action

Domperidone blocks dopamine D₂ receptors:

• In the gastrointestinal tract: Enhances gastric emptying, increases lower esophageal sphincter tone, and reduces small bowel transit time.

• At the chemoreceptor trigger zone (CTZ): Located in the area postrema (outside the BBB), it suppresses nausea and vomiting signals.

Unlike other D₂ antagonists, domperidone has minimal central nervous system penetration, reducing the risk of extrapyramidal side effects (EPS).

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Approved Indications

Adults

• Nausea and vomiting, including from gastroenteritis, medication, or post-operative causes

• Gastroesophageal reflux symptoms, especially in combination with PPIs

• Gastroparesis (especially diabetic gastroparesis)

• Functional dyspepsia with delayed gastric emptying

• Prokinetic support in tube feeding (e.g., in ICU)

Pediatrics

• Limited use in children with severe nausea/vomiting or feeding intolerance

• Contraindicated in infants <1 year due to risk of cardiac arrhythmias

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Dosage and Administration

Adults

• Standard dose: 10 mg orally up to three times daily before meals

• Maximum duration: Recommended for short-term use (≤7 days)

• Maximum dose: 30 mg/day (due to cardiac risk)

Elderly (≥60 years)

• Should be used with caution or avoided due to increased cardiac sensitivity

Children (older than 12 years or >35 kg)

• 10 mg up to three times daily

• Oral suspension: dose adjusted based on weight (0.25–0.5 mg/kg up to 3 times/day)

Administration tips

• Give 15–30 minutes before meals

• Should not be taken with grapefruit juice (CYP3A4 inhibitor)

• Do not exceed duration or dose without clinical justification

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Contraindications

• Known prolonged QT interval

• Concurrent use with QT-prolonging drugs (e.g., erythromycin, ketoconazole, fluconazole, citalopram, amiodarone)

• Severe liver impairment

• Gastrointestinal hemorrhage, mechanical obstruction, or perforation

• Hypersensitivity to domperidone or excipients

• Children under 1 year of age

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Warnings and Precautions

• QT prolongation and ventricular arrhythmias, including torsades de pointes

• Risk increased with:

  • Age >60

  • Daily doses >30 mg

  • Co-administration with CYP3A4 inhibitors

• Cardiovascular monitoring may be required in high-risk patients

• Use with caution in patients with electrolyte imbalance (hypokalemia, hypomagnesemia)

• Monitor liver function if prolonged use

• Breast milk production: Domperidone stimulates prolactin release, used off-label to induce lactation but discouraged by FDA and EMA due to cardiac concerns

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Adverse Effects

Common (1–10%)

• Dry mouth

• Abdominal cramps, flatulence, diarrhea

• Headache, dizziness

• Somnolence (rarely, despite limited CNS penetration)

• Increased prolactin → galactorrhea, gynecomastia, menstrual irregularities

Uncommon/Rare (<1%)

• Extrapyramidal symptoms: Dystonia, akathisia (mostly in infants or high-dose cases)

• Allergic reactions, rash, pruritus

• QT interval prolongation, arrhythmia, sudden cardiac death (in overdose or risk groups)

• Hepatotoxicity (rare)

• Neuroleptic malignant syndrome (very rare)

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Drug Interactions

Increased risk of QT prolongation or arrhythmia with:

• Macrolide antibiotics: erythromycin, clarithromycin

• Azole antifungals: ketoconazole, itraconazole, fluconazole

• Antidepressants: citalopram, escitalopram, amitriptyline

• Antipsychotics: haloperidol, pimozide

• Antiarrhythmics: amiodarone, sotalol

• HIV protease inhibitors: ritonavir, nelfinavir

CYP3A4 inhibitors:

• Inhibit metabolism of domperidone → elevated serum levels → higher cardiac risk

• Examples: diltiazem, verapamil, grapefruit juice

Anticholinergics:

• May antagonize domperidone’s GI prokinetic effect

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Use in Special Populations

Pregnancy

• Category C (FDA): No controlled studies; limited human data

• Used when benefit outweighs risk, especially for hyperemesis gravidarum

• Not teratogenic in animal models

Lactation

• Excreted in breast milk in small amounts

• Risk of QT prolongation in neonates is uncertain

• Not recommended for inducing lactation due to cardiac risk

Elderly

• Increased sensitivity to QT effects

• Start at lower doses or avoid altogether

Pediatrics

• Not for children under 1 year

• Older children: Weight-based dosing; short-term only

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Overdose and Management

Symptoms

• Sedation, disorientation, extrapyramidal effects

• Cardiac toxicity, including QT prolongation

• Seizures in rare cases

Treatment

• Symptomatic management

• Activated charcoal if within 1 hour

• ECG monitoring

• No specific antidote available

• Avoid antiemetics with QT risk (e.g., ondansetron) in overdose

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Clinical Guidelines and Regulatory Position

• EMA (European Medicines Agency): 2014 restriction – Max dose 30 mg/day, limit to nausea and vomiting only, short-term use

• MHRA (UK): Supports EMA restriction; contraindicated in cardiac risk patients

• FDA (US): Not approved for any indication; issued warnings against use to promote lactation

• WHO: Not included on essential medicines list due to safety profile

• Australia: PBS listing for nausea/vomiting under specialist supervision

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Comparative Insights (No Tables)

Domperidone vs. Metoclopramide

• Metoclopramide crosses the BBB → higher CNS side effect risk (e.g., EPS, drowsiness)

• Domperidone has fewer extrapyramidal effects but higher cardiac risk at high doses

• Metoclopramide is preferred in severe gastroparesis under monitoring

• Domperidone often better tolerated in older patients (within dosing limits)

Domperidone vs. Ondansetron

• Ondansetron is a 5-HT₃ antagonist used in chemotherapy-related nausea

• Domperidone is more effective for GI motility-related symptoms

• Ondansetron has its own QT prolongation risk, but less dopaminergic impact

• Domperidone also increases prolactin; ondansetron does not

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Patient Counseling Points

• Take 15–30 minutes before meals

• Do not exceed 3 doses per day (10 mg each)

• Do not use for longer than 7 days without physician review

• Avoid grapefruit juice

• Seek medical attention if experiencing palpitations, fainting, or chest pain

• Report galactorrhea, breast swelling, or menstrual changes

• Inform doctor of all current medications to avoid interactions

• Store at room temperature, away from moisture and heat