What is the recommended dosage of domperidone (antiemetic medication) for adults and children?

Domperidone Dosage Recommendations

Domperidone should be dosed at 10 mg three to four times daily (30-40 mg/day total) in adults, with a maximum of 30 mg/day for routine use due to significant cardiac safety concerns, though doses up to 120 mg/day have been used in refractory gastroparesis under close cardiac monitoring. 1, 2, 3

Adult Dosing

Standard Dosing for Gastroparesis and Nausea

• The typical adult dose is 10 mg orally three to four times daily (total 30-40 mg/day) 1, 2
• Studies in diabetic gastroparesis have shown efficacy with 40-80 mg/day divided into multiple doses 2
• The defined daily dose of 30 mg/day represents the standard therapeutic target 4

High-Dose Regimens (Refractory Cases Only)

• Doses up to 120 mg/day have been used in patients with refractory gastroparesis who failed other therapies, but this requires intensive cardiac monitoring 2, 3
• A retrospective study of 21 patients used a mean highest dose of 80 mg/day (range 40-120 mg) for an average of 52 months, with 82% improvement in vomiting severity 3
• Doses above 30 mg/day carry substantially increased risk of sudden cardiac death, with odds ratios rising sharply above this threshold 4, 5

Pediatric Dosing

Children and Infants

• The recommended dose is 0.2 mg/kg three times daily (0.6 mg/kg/day total) for infants and children 1
• An alternative dosing of 2 mg/kg/day divided four times daily has been used in children aged 1 month to 12.7 years with 100% symptom improvement 1
• Domperidone showed comparable efficacy to cisapride at 0.2 mg/kg three times daily in 55 infants, with 64.5% improvement in cough symptoms 1

Critical Safety Considerations

Cardiac Monitoring Requirements

• Baseline and periodic ECG monitoring is mandatory, particularly for QTc interval assessment 1, 3
• The National Patient Safety Agency has issued alerts regarding QTc prolongation with domperidone, requiring long-term QTc monitoring 1
• Two patients (9.5%) taking 120 mg/day experienced asymptomatic QTc prolongation (>450 ms in males, >470 ms in females) in one study 3
• The drug has an extremely narrow safety margin with a safety index of only ~2.5, which is 12-fold below the accepted minimum 4

Contraindications and High-Risk Situations

• Avoid in patients >60 years old when possible, as five population-based studies show domperidone increases odds ratio for sudden cardiac death to 2.8 (range 1.53-6.21) in older adults 4, 5
• Do not combine with strong or moderate CYP3A4 inhibitors (co-prescribed in 4.3% and 10.7% of older users respectively, inappropriately) 6
• Avoid co-prescribing with medications that prolong QT interval or cause torsades de pointes (inappropriately co-prescribed in 18.3-18.8% of older users) 6
• Contraindicated in patients with prolactinoma, gastrointestinal hemorrhage or obstruction, and those with baseline QTc prolongation 3

Duration of Therapy

• The European Medicines Agency recommends against long-term use due to cardiac risks and lack of consistent benefit 1
• However, therapeutic benefits have been maintained for up to 12 years in some diabetic gastroparesis patients at 40-80 mg/day 2
• If used long-term, the lowest effective dose should be maintained with regular cardiac monitoring 1, 3

Clinical Efficacy Context

When Domperidone May Be Appropriate

• Domperidone 40-80 mg/day may be effective in patients refractory to metoclopramide 2
• It has a better tolerability profile than metoclopramide 40 mg/day regarding extrapyramidal side effects 2
• As a selective peripheral D2 dopamine receptor antagonist, it does not cross the blood-brain barrier easily, avoiding central nervous system effects 1, 2

Important Limitations

• The defined daily dose of 30 mg/day fails to show unequivocal gastrointestinal benefits beyond placebo effect 4
• Despite this, 66-88% of patients with diabetic gastropathy showed significant symptom improvement from baseline 2
• Quality of life improvements and reduced hospitalization rates have been documented at 40-120 mg/day 2

Practical Algorithm for Dosing

1. Start with 10 mg three times daily (30 mg/day total) in adults with gastroparesis or nausea 1, 2
2. Obtain baseline ECG before initiating therapy to assess QTc interval 1, 3
3. Screen for drug interactions, particularly CYP3A4 inhibitors and QT-prolonging medications 6
4. If inadequate response after 2-4 weeks, consider increasing to 10 mg four times daily (40 mg/day) 2
5. For refractory cases only, doses may be titrated up to 80-120 mg/day under specialist supervision with frequent ECG monitoring 3
6. Repeat ECG at dose escalations and every 3-6 months during maintenance therapy 1, 3
7. Discontinue immediately if QTc >450 ms (males) or >470 ms (females), or if patient develops palpitations or syncope 3