What is the recommended dose of domperidone (Domperidone) for treating gastroparesis?

Domperidone Dosing for Gastroparesis

The recommended dose of domperidone for gastroparesis is 10 mg three to four times daily (TID-QID), typically totaling 30-40 mg per day, though doses up to 20 mg QID (80 mg/day) have been used in clinical practice. 1, 2, 3

Standard Dosing Regimen

• Start with 10 mg TID or QID as the initial therapeutic dose for gastroparesis symptoms 1, 2
• The most commonly studied and prescribed regimen is 10 mg four times daily (40 mg/day total) 4, 5, 6
• Some patients may require dose escalation to 20 mg QID (80 mg/day) for optimal symptom control, though this is less common 4, 6
• Average effective doses in clinical practice range from 36-40 mg/day 3, 6

Important Context and Positioning

Domperidone is NOT FDA-approved in the United States but is available in Canada, Mexico, and Europe 1. In the U.S., it can only be obtained through an FDA investigational drug protocol, and doses above 10 mg TID are not recommended due to QT prolongation risk 1.

Treatment Hierarchy

Domperidone should be considered as an alternative prokinetic agent when:

• Metoclopramide is contraindicated or not tolerated (metoclopramide is the only FDA-approved agent for gastroparesis but carries significant extrapyramidal side effect risks) 1
• Patients have failed or cannot tolerate metoclopramide beyond the FDA-recommended 12-week limit 1

Expected Timeline and Efficacy

• Symptom improvement typically begins by day 3 of treatment and is maintained throughout therapy 2
• Optimal assessment of response should occur at 2-3 months of treatment 3
• Long-term treatment (average 23 months in studies) has demonstrated sustained efficacy and safety 4

Symptoms Most Responsive to Domperidone

The following symptoms show significant improvement with domperidone therapy:

• Postprandial fullness (most responsive) 2, 3
• Nausea 2, 3
• Vomiting 3, 4
• Early satiety 2, 6
• Abdominal bloating/distention 5, 6

Safety Profile and Monitoring

Common Side Effects

Approximately 38% of patients experience side effects, though only 12-14% discontinue treatment due to adverse effects 3. The most common side effects include:

• Headache 3
• Tachycardia/palpitations 2, 3
• Diarrhea 3
• Breast tenderness 2
• Gynecomastia (due to prolactin elevation, mean prolactin level 58.9 pg/ml) 4

Critical Safety Considerations

QT prolongation is a significant concern with domperidone, particularly at higher doses:

• Obtain baseline ECG to assess QTc interval before initiating therapy (normal: <450 ms in men, <460 ms in women) 7
• Correct electrolyte abnormalities (hypokalemia, hypomagnesemia) before starting treatment, as these potentiate QT prolongation risk 7
• Screen for contraindications: prolonged baseline QTc (>500 ms), concurrent QT-prolonging medications, severe electrolyte disturbances, history of torsades de pointes 7

Comparative Safety Advantage

Domperidone has significantly fewer CNS side effects compared to metoclopramide 5:

• Somnolence: 29% with domperidone vs 49% with metoclopramide (p=0.02) 5
• Reduced mental acuity: 20% with domperidone vs 33% with metoclopramide (p=0.04) 5
• Lower rates of akathisia, asthenia, anxiety, and depression compared to metoclopramide 5

Clinical Outcomes

Studies demonstrate that 77% of patients show improvement with domperidone treatment, with 45% achieving at least moderate improvement 3. Treatment results in:

• Significant reduction in gastroparesis symptom scores (from 4.1 to 1.3 on a 0-5 scale) 4
• Decreased hospitalizations for gastroparesis symptoms 4
• Improved quality of life in 88% of patients 4
• Acceleration of gastric emptying (solid meal retention decreased from 87.3% to 57.2% at 2 hours) 4

Common Pitfalls to Avoid

• Do not exceed 10 mg TID in the U.S. due to increased QT prolongation risk at higher doses 1
• Do not prescribe without baseline ECG and electrolyte assessment 7
• Do not use in patients with Parkinson's disease due to dopamine antagonism 7
• Do not combine with other QT-prolonging medications without careful monitoring 7
• Remember this requires FDA investigational drug protocol access in the U.S., limiting availability 1, 3