In an adult with nausea, vomiting, or gastroparesis, should metoclopramide (Reglan) be used as first‑line instead of domperidone, and what are the recommended dosing and safety monitoring?

Metoclopramide vs Domperidone for Nausea, Vomiting, and Gastroparesis

Metoclopramide should be used as first-line therapy for adults with nausea, vomiting, or gastroparesis, starting at 5–20 mg three to four times daily (30 minutes before meals and at bedtime), because it is the only FDA-approved prokinetic agent for gastroparesis and has both central antiemetic and peripheral prokinetic effects. 1, 2

Why Metoclopramide is First-Line

• The American Gastroenterological Association explicitly recommends metoclopramide as the first-line medication choice for gastroparesis-related nausea and vomiting due to its dual mechanism: dopamine D2-receptor antagonism (antiemetic effect) plus enhancement of gastric motility (prokinetic effect). 1, 2

• Metoclopramide is the only FDA-approved drug specifically for gastroparesis in the United States, reflecting its established efficacy and regulatory scrutiny. 3

• The recommended starting dose is 5–10 mg orally three to four times daily, taken 30 minutes before meals and at bedtime, with titration up to 20 mg per dose based on response. 2

When to Consider Domperidone (Second-Line)

Domperidone 10 mg three times daily should be reserved for patients who fail metoclopramide therapy after at least 4 weeks of adequate dosing, or for those who develop intolerable extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) on metoclopramide. 1, 2, 3

Key advantages of domperidone:

• Does not readily cross the blood-brain barrier, resulting in significantly fewer central nervous system side effects (extrapyramidal symptoms, tardive dyskinesia) compared to metoclopramide. 1, 3

• In a single-center cohort of 115 gastroparesis patients, 68% reported symptom improvement on domperidone, with particular benefit for postprandial fullness, nausea, vomiting, and stomach fullness. 1, 4

• Preferred for long-term therapy (beyond 12 weeks) when metoclopramide's neurological risks become prohibitive. 3

Critical limitations of domperidone:

• Availability in the United States requires an FDA investigational drug application, making it inaccessible for routine first-line use. 1, 3

• Carries risk of QT prolongation and ventricular tachycardia, particularly at doses above 30 mg/day or in patients over 60 years old. 1, 3

• The recommended starting dose is 10 mg three times daily; escalation to 20 mg four times daily should be avoided due to cardiovascular safety concerns. 1

Safety Monitoring Requirements

For Metoclopramide:

• Monitor for extrapyramidal symptoms (dystonia, akathisia) at every visit, particularly in young males who are at highest risk. 5, 6

• The FDA restricts chronic use beyond 12 weeks due to risk of tardive dyskinesia, which can be irreversible. 1, 3

• Treat acute dystonic reactions with diphenhydramine 50 mg IV immediately. 1

For Domperidone:

• Obtain baseline ECG in patients over 60 years old, those with cardiac risk factors, or when prescribing doses above 30 mg/day. 3

• Avoid combining with other QT-prolonging agents (e.g., ondansetron) without ECG monitoring. 2, 3

• In the largest single-center study, 12% of patients discontinued domperidone due to side effects (most commonly headache, tachycardia/palpitations, diarrhea). 4

Treatment Algorithm

1. Weeks 0–4: Start metoclopramide 5–10 mg three to four times daily (30 minutes before meals and at bedtime) plus dietary modifications (small, frequent meals; low-fat, low-fiber diet). 2

2. Weeks 4–8: If inadequate response, titrate metoclopramide to 20 mg per dose (maximum 80 mg/day). 2

3. Week 8+: If metoclopramide fails or causes intolerable side effects, switch to domperidone 10 mg three times daily (if accessible via FDA IND application). 1, 2, 3

4. Adjunctive therapy: Add 5-HT3 antagonist (ondansetron 4–8 mg two to three times daily) if nausea persists after 4 weeks of adequate prokinetic therapy. 1, 2

Critical Pitfalls to Avoid

• Never combine metoclopramide and domperidone concurrently—they share the same dopamine D2-receptor antagonist mechanism and provide no additive benefit, only additive risks. 3

• Do not use either agent in patients with mechanical bowel obstruction, as this can mask progressive ileus. 5

• Avoid metoclopramide in patients on chronic opioids, as opioids are an absolute contraindication to gastric electrical stimulation and suggest a different underlying pathophysiology. 2

• Do not prescribe domperidone as first-line in the United States due to regulatory restrictions requiring investigational drug application. 1, 3

Alternative Options When Both Fail

• Transdermal granisetron patch (3.1 mg/24 hours) has demonstrated 50% reduction in symptom scores in refractory gastroparesis. 1

• NK-1 receptor antagonists (aprepitant 125 mg/day) showed improvement in nausea and vomiting in an RCT of 126 gastroparesis patients. 1

• Consider gastric electrical stimulation for patients with refractory nausea/vomiting who have failed medical therapy for >18 months, are not on opioids, and do not have abdominal pain as the predominant symptom. 2