What is the recommended treatment protocol for vomiting using domperidone?

Domperidone for Vomiting: Treatment Protocol

For vomiting, domperidone should be initiated at 10 mg three times daily (30 minutes before meals), with a maximum dose of 20 mg three to four times daily if needed, though doses above 30 mg/day significantly increase cardiac risk and should be avoided. 1

Clinical Context and Indications

Domperidone is a dopamine D2-receptor antagonist that does not readily cross the blood-brain barrier, resulting in fewer extrapyramidal side effects compared to metoclopramide. 1 It is effective for:

• Gastroparesis-related vomiting (diabetic or idiopathic) 2, 1
• Chemotherapy-induced nausea and vomiting, particularly when added to serotonin antagonists and corticosteroids for refractory cases 1
• Functional dyspepsia with early satiety 1
• Migraine-associated nausea and vomiting as an adjunct oral medication 2

Dosing Algorithm

Starting Dose

• Begin with 10 mg orally three times daily, taken 30 minutes before meals 1
• This lower starting dose minimizes QT prolongation risk while maintaining efficacy 1

Dose Escalation

• If inadequate response after 2-3 days, increase to 20 mg three times daily 1
• Maximum dose: 20 mg four times daily (80 mg/day), though staying at or below 30 mg/day total is strongly preferred for cardiac safety 1, 3

Duration of Effect

• Each dose provides antiemetic effect for approximately 7-14 hours based on its pharmacokinetic profile 1
• Plasma half-life is approximately 7.5 hours 1

Critical Safety Considerations

Cardiovascular Monitoring

QT prolongation and risk of torsade de pointes are the primary safety concerns, particularly at doses >30 mg/day and in patients >60 years old. 1, 4

Mandatory precautions include:

• Baseline ECG before initiating therapy, especially in high-risk patients 1
• Avoid in patients with: pre-existing QT prolongation, electrolyte disorders (hypokalemia, hypomagnesemia), or concomitant use of QT-prolonging medications 4
• Consider repeat ECG monitoring if dose exceeds 30 mg/day or if cardiovascular risk factors are present 1

Evidence on High-Dose Safety

One retrospective study of 64 patients receiving 80-120 mg/day (2-fold higher than standard dosing) for mean duration of 8 months showed 73% clinical benefit with low cardiovascular event rates, though 10 of 37 patients developed prolonged QTc without symptoms. 3 However, this does not justify routine high-dose use given guideline warnings about cardiac risk. 1, 4

When NOT to Use Domperidone

Long-term Use Restrictions

The British Society of Gastroenterology explicitly states that domperidone should no longer be used in the long term for chronic gastrointestinal motility disorders due to cumulative cardiac risks. 2, 4

Functional Bloating

Do not use domperidone for functional bloating - the American Gastroenterological Association found no evidence of effectiveness, and cardiac risks outweigh unproven benefits. 4

Comparison with Alternative Antiemetics

Domperidone vs. Metoclopramide

• Domperidone is preferred for prolonged therapy due to significantly lower risk of extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) 1
• Metoclopramide carries high risk of irreversible tardive dyskinesia and is FDA-approved only for gastroparesis 1
• In pediatric patients and those with Parkinson's disease, domperidone is strongly preferred 1

Alternative Options When Domperidone is Unavailable or Contraindicated

• 5-HT3 antagonists (ondansetron 4-8 mg 2-3 times daily): First-line for chemotherapy-induced vomiting, though can worsen constipation 2, 1
• Metoclopramide (5-20 mg 3-4 times daily): If short-term use only, monitor for extrapyramidal effects 1
• Prochlorperazine (5-10 mg four times daily): For refractory cases, but monitor for dystonic reactions 1, 5

Efficacy Evidence

Pediatric Data

Early studies showed domperidone 0.3 mg/kg three times daily was significantly more effective than both metoclopramide and placebo in controlling chronic vomiting in children. 6 Single-dose parenteral or rectal administration controlled severe vomiting within 3 hours in 88% of pediatric patients. 7

Adult Efficacy

In adults with gastroparesis receiving high-dose therapy (80-120 mg/day), 73% experienced reduced nausea and vomiting over mean treatment duration of 8 months. 3

Common Pitfalls to Avoid

• Do not exceed 30 mg/day without compelling indication and cardiac monitoring - risk of QT prolongation increases substantially 1, 4
• Do not use for postoperative nausea and vomiting - droperidol is significantly more effective in this setting 8
• Do not continue indefinitely without reassessment - cumulative cardiac risk increases with prolonged use 4
• Do not combine with other QT-prolonging medications without cardiology consultation 4

Regulatory Status Note

Domperidone is not FDA-approved in the United States but is widely available in Canada, Mexico, and Europe. 2 In the U.S., it requires an Investigational New Drug (IND) application protocol for use. 3