What are the indications, adult dosing schedule, maximum duration, contraindications, cardiac monitoring recommendations, and alternative therapies for domperidone?

Domperidone: Clinical Use and Management

Indications

Domperidone is indicated for nausea and vomiting associated with gastroparesis, functional dyspepsia with early satiety/bloating, and chemotherapy-induced nausea and vomiting. 1

• Gastroparesis (diabetic or idiopathic): Domperidone is recommended by the American Gastroenterological Association as a preferred agent due to its lower risk of extrapyramidal side effects compared to metoclopramide 1
• Functional dyspepsia: Specifically for patients with predominant symptoms of fullness, bloating, or early satiety (dysmotility-like dyspepsia), rather than epigastric pain 1
• Chemotherapy-induced nausea and vomiting: Particularly useful when added to serotonin antagonists and corticosteroids for refractory cases 1
• Migraine-associated nausea and vomiting: As an adjunct oral medication 1
• GERD with documented motility disturbances: Reserved only for patients who have failed PPI therapy and have documented delayed gastric emptying 2

Adult Dosing Schedule

Start with 10 mg three times daily, with a maximum dose of 20 mg three to four times daily, avoiding total daily doses exceeding 30 mg/day when possible. 1, 3

• Initial dose: 10 mg three times daily (30 mg/day total) minimizes cardiovascular risk while providing prokinetic and antiemetic effects 1, 3
• Maximum dose: 20 mg three to four times daily (60-80 mg/day total) if response is inadequate 3
• Chemotherapy settings: Typically 20 mg administered 3-4 times daily 1
• Dose escalation: Avoid exceeding 30 mg/day without carefully considering cardiovascular risk 3

Maximum Duration of Treatment

Domperidone should not be used long-term beyond 12 weeks due to cumulative cardiac risks. 2, 3

• The British Society of Gastroenterology explicitly states domperidone should no longer be used long-term for chronic gastrointestinal motility disorders 1
• The European Medicines Agency recommends against long-term use of prokinetic agents like domperidone 2, 3
• For initial trials, the American Gastroenterological Association suggests 2-4 weeks of empirical therapy 1
• If therapy is required beyond 12 weeks, strongly consider alternatives such as 5-HT3 receptor antagonists (ondansetron) or prucalopride 2

Contraindications

Domperidone is contraindicated in patients with pre-existing QTc prolongation, electrolyte abnormalities (hypokalemia, hypomagnesemia), and concomitant use of QT-prolonging medications or CYP3A4 inhibitors. 3, 4

• Cardiac conditions: Pre-existing QTc prolongation or Long QT Syndrome 4
• Electrolyte abnormalities: Hypokalemia, hypomagnesemia 3, 4
• Drug interactions: Concurrent use of CYP3A4 inhibitors or other QT-prolonging medications 4
• Pregnancy considerations: Should not be used during pregnancy (safer alternatives like aprepitant are available) 5

Cardiac Monitoring Recommendations

Obtain a baseline ECG before initiating therapy, especially in patients over 60 years old, those with cardiac risk factors, or those receiving doses over 30 mg/day. 1, 3

• Pre-treatment screening: The American Heart Association advises assessing cardiac risk factors due to QT prolongation risk 1
• Baseline ECG: The European Society of Cardiology recommends obtaining baseline ECG if patient is over 60 years old, has cardiac risk factors, or will receive doses over 30 mg/day 1
• Ongoing monitoring: Regular QTc monitoring via ECG is recommended, particularly for prolonged therapy 2, 3
• Electrolyte monitoring: Screen for and correct hypokalemia and hypomagnesemia before and during therapy 3
• High-risk populations: Patients over 60 years have significantly higher risk of cardiac complications 2, 3

Key Safety Considerations

The primary safety concern is QT prolongation and risk of torsades de pointes, particularly with doses exceeding 30 mg/day and in patients over 60 years old. 1, 2

• The European Society for Clinical Nutrition and Metabolism highlights that domperidone can prolong QTc interval and potentially cause life-threatening arrhythmias, especially with doses over 30 mg/day 1
• Cardiovascular risks increase significantly in patients over 60 years old 1, 2
• Despite cardiovascular risks, domperidone is still preferred over metoclopramide for prolonged therapy due to its superior neurological profile 1
• Domperidone does not readily cross the blood-brain barrier, resulting in fewer central nervous system side effects compared to metoclopramide 1
• Prolactin elevation occurs in all patients but prolactin-related adverse events (gynecomastia) occur in only 10-20% 6, 7

Alternative Therapies

If domperidone is unavailable or contraindicated, alternatives include metoclopramide (5-20 mg three to four times daily for ≤12 weeks), ondansetron (4-8 mg two to three times daily), or prochlorperazine (5-10 mg four times daily). 1, 2

First-line alternatives:

• 5-HT3 receptor antagonists (ondansetron): 4-8 mg twice or three times daily, particularly effective for chemotherapy-induced vomiting 1, 2
• Metoclopramide: 5-20 mg three to four times daily, but limited to 12 weeks maximum due to FDA black box warning for tardive dyskinesia 1, 2
• Prochlorperazine: 5-10 mg four times daily 1

For specific conditions:

• Prucalopride: First-line prokinetic agent without cardiac effects for severe gastroparesis 2, 3
• Baclofen (GABA agonist): Decreases 24-hour acid exposure and reflux episodes in GERD, though limited by CNS side effects 2
• Alginates added to PPI: Showed significantly greater complete heartburn resolution in NERD patients 2

Important Clinical Pitfalls

Never combine domperidone with metoclopramide—they are alternative treatments, not complementary therapies, with overlapping mechanisms and additive risks without demonstrated additional benefit. 1

• Both are dopamine D2-receptor antagonists working through the same mechanism 1
• The American Diabetes Association lists them as alternative options, not complementary therapies 1
• No studies demonstrate added benefit of combining these agents 1
• Appropriate approach is sequential use: start with domperidone, then switch (not add) to metoclopramide if domperidone fails 1

Do not use domperidone routinely for GERD without documented motility disturbances—it has only modest effect and should be reserved for PPI-refractory cases with proven delayed gastric emptying. 2

Prioritize cardiovascular safety over aggressive dose escalation—avoid exceeding 30 mg/day without carefully weighing risks. 3