What is the recommended adult dosage of domperidone for gastroparesis, including adjustments for renal or hepatic impairment?

Domperidone Dosing for Delayed Gastric Emptying

The recommended adult dosage of domperidone for gastroparesis is 10 mg three times daily (TID), taken 30 minutes before meals, and should not be escalated beyond this dose due to cardiovascular safety concerns. 1, 2

Standard Dosing Protocol

• Start with 10 mg TID or QID as the initial and maintenance therapeutic dose for gastroparesis symptoms 2
• Administer 30 minutes before meals to optimize prokinetic effect 1
• Do not exceed 10 mg TID due to increased QT prolongation risk at higher doses 1, 2

Treatment Positioning in Algorithm

• Domperidone should be used as a third-line option only after failure of first-line metoclopramide (minimum 10 mg three times daily for at least 4 weeks) combined with dietary modifications (small particle size, low-fat diet for minimum 4 weeks) 1
• Consider domperidone as an alternative prokinetic agent when metoclopramide is contraindicated or not tolerated 2
• Domperidone has significantly fewer CNS side effects compared to metoclopramide, making it preferable in patients who develop extrapyramidal symptoms 2

Pre-Treatment Requirements

• Obtain baseline ECG to assess QTc interval before initiating therapy (normal values: <450 ms in men, <460 ms in women) 2
• Correct electrolyte abnormalities (hypokalemia, hypomagnesemia) before starting treatment, as they potentiate QT prolongation risk 2
• Screen for contraindications including prolonged baseline QTc (>500 ms), concurrent QT-prolonging medications (e.g., ondansetron), severe electrolyte disturbances, history of torsades de pointes, and Parkinson's disease 3, 2

Dose Adjustments for Organ Impairment

The provided evidence does not contain specific dosing adjustments for renal or hepatic impairment. However, given the cardiac safety concerns, maintain the standard 10 mg TID dose without escalation in any patient population and increase monitoring frequency in patients with organ dysfunction 2.

Availability and Access Limitations

• Domperidone is NOT FDA-approved in the United States but is available in Canada, Mexico, and Europe 2
• In the U.S., domperidone requires an investigational new drug (IND) application to the FDA for compassionate use 1, 4
• This restricted availability is a major limitation despite its efficacy 1

Expected Clinical Response

• Symptom improvement typically occurs within 3 days of treatment initiation and is maintained during continued therapy 5
• Domperidone is particularly effective for nausea, vomiting, postprandial fullness, and early satiety—the hallmark symptoms of gastroparesis 1, 5
• In clinical studies, 68% of patients experienced symptom improvement, with the majority reporting at least moderate benefit 1, 4

Common Side Effects and Monitoring

• Most common side effects include headache (reported in multiple patients), tachycardia/palpitations, diarrhea, breast tenderness, and menstrual irregularities 4, 5
• Approximately 12% of patients discontinue treatment due to side effects 4
• Cardiac side effects requiring discontinuation occur in approximately 7% of patients, primarily QT prolongation 1
• Extrapyramidal side effects are significantly less frequent than with metoclopramide due to limited blood-brain barrier penetration 1, 2

Critical Pitfalls to Avoid

• Never escalate to 20 mg four times daily despite historical use of this regimen, as cardiovascular safety concerns preclude higher dosing 1, 2
• Do not prescribe without baseline ECG and electrolyte assessment 2
• Exercise caution when combining with other QT-prolonging agents such as ondansetron, which is commonly used as a second-line antiemetic in gastroparesis 1
• Do not use in patients with Parkinson's disease due to dopamine antagonism 2
• Do not use in patients with prolactinoma, gastrointestinal hemorrhage or obstruction, or in pregnant/breastfeeding females 6

Evidence Quality Note

While higher doses (40-120 mg/day) have been studied in refractory cases with some success 6, current guideline recommendations from the American Gastroenterological Association and FDA safety concerns support limiting dosing to 10 mg TID 1, 2. The cardiovascular risk-benefit ratio does not support routine dose escalation in clinical practice.