What are the recommended adult dosing, duration, contraindications, and safety precautions for domperidone?

Domperidone: Dosing, Duration, Contraindications, and Safety

For adult patients requiring domperidone, start with 10 mg three times daily before meals (maximum 20 mg three to four times daily), limit treatment duration to the shortest effective period due to cardiac risks, and screen for QT prolongation risk factors before prescribing. 1

Adult Dosing Recommendations

Starting dose:

• Begin with 10 mg orally three times daily, taken 15-30 minutes before meals 1
• This lower starting dose minimizes QT prolongation risk while providing therapeutic benefit 1

Maximum dosing:

• Do not exceed 20 mg three to four times daily (maximum 80 mg/day) 1
• Avoid doses above 30 mg/day when possible to reduce cardiac complications 1, 2
• In chemotherapy-induced nausea/vomiting, 20 mg three to four times daily is standard 1

Duration of action:

• Each dose provides symptom relief for approximately 7-14 hours 1
• Plasma half-life is 7.5 hours, supporting three-times-daily dosing 1

Treatment Duration

General principle:

• Use the shortest effective treatment period due to cumulative cardiac risks 3
• The British Society of Gastroenterology explicitly states domperidone should no longer be used long-term for chronic gastrointestinal motility disorders 1

Initial trial period:

• For functional dyspepsia: 2-4 weeks of empirical therapy 1
• If symptoms improve, attempt trial withdrawal and resume only if symptoms recur 1

Long-term considerations:

• While some studies show efficacy maintained up to 12 years in diabetic gastroparesis 4, current guidelines emphasize caution with prolonged use due to cardiac safety concerns 1, 2
• Regular cardiac monitoring is essential if extended therapy is unavoidable 2

Absolute Contraindications

Cardiac contraindications:

• Pre-existing QT prolongation or Long QT Syndrome 2, 5
• Concurrent use of CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin, ritonavir) 2, 5
• Electrolyte abnormalities (hypokalemia, hypomagnesemia) 2, 5
• Concurrent use of other QT-prolonging medications 2

Gastrointestinal contraindications:

• Mechanical gastrointestinal obstruction 2
• Gastrointestinal hemorrhage 2
• Gastrointestinal perforation 2

Safety Precautions and Monitoring

Pre-Treatment Cardiac Screening

Risk assessment algorithm:

1. Obtain baseline ECG if patient is >60 years old 1
2. Obtain baseline ECG if cardiac risk factors present (hypertension, diabetes, coronary artery disease) 1
3. Obtain baseline ECG if planned dose >30 mg/day 1
4. Check baseline electrolytes (potassium, magnesium) 2, 5

Ongoing Monitoring

For patients on therapy:

• Regular QTc monitoring during long-term therapy 2
• Periodic electrolyte monitoring 2
• Monitor for signs/symptoms of arrhythmia (palpitations, syncope, dizziness) 2, 5

Cardiac Risk Profile

Key safety considerations:

• QT prolongation and torsade de pointes are the primary concerns 1, 2, 5
• Risk increases significantly with doses >30 mg/day 1, 2
• Risk increases in patients >60 years old 1, 2
• Intravenous administration carries higher cardiac risk than oral 1

Neurological Safety Advantage

Compared to metoclopramide:

• Domperidone does not readily cross the blood-brain barrier 6, 7
• Extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) are rare 6, 7
• This makes domperidone strongly preferred over metoclopramide for extended therapy 1, 3

Special Populations

Adolescents (12-17 years)

• Can use domperidone for nausea, though oral administration unlikely to prevent vomiting 8
• Preferred over metoclopramide due to lower extrapyramidal risk 1

Pregnant Women

• Metoclopramide is preferred for nausea in pregnancy (not domperidone) 8
• Use only under specialist supervision if domperidone is considered 8

Breastfeeding Women

• Milk:plasma ratio is 0.25 with relative infant dose of 0.01-0.35% 1
• May be used as galactogogue in healthy women without direct risk, but FDA has issued warnings 5
• More safety data needed regarding risk to breastfeeding infants 5

Diabetic Gastroparesis

• Domperidone 40-80 mg/day significantly improves gastric emptying and symptoms 4
• Cardiac risks must be carefully weighed against benefits in this population 2
• May be effective in patients refractory to metoclopramide 4

Clinical Applications

Approved indications:

• Gastroparesis (diabetic or idiopathic) 1, 4
• Functional dyspepsia with fullness, bloating, or early satiety 1
• Chemotherapy-induced nausea and vomiting 1
• Migraine-associated nausea and vomiting (as adjunct) 1

Symptom-based selection:

• For dysmotility-like symptoms (fullness, bloating, early satiety): domperidone is first-line 1
• For epigastric pain-predominant dyspepsia: start with PPI therapy instead 1

Alternative Agents When Domperidone Unavailable or Contraindicated

Sequential treatment algorithm:

1. If domperidone fails or unavailable: switch to metoclopramide 5-20 mg three to four times daily (not add to domperidone) 1
2. For chemotherapy-induced vomiting: 5-HT3 antagonists (ondansetron 4-8 mg 2-3 times daily) 1
3. Other alternatives: prochlorperazine 5-10 mg four times daily 1

Never combine domperidone with metoclopramide:

• Both are dopamine D2-receptor antagonists with overlapping mechanisms 1
• No demonstrated additional benefit from combination 1
• Additive risk profiles without therapeutic gain 1

Common Pitfalls to Avoid

Dosing errors:

• Never exceed 30 mg/day without compelling reason and cardiac monitoring 1, 2
• Don't use domperidone long-term without periodic reassessment of need 1, 3

Screening failures:

• Don't ignore cardiac screening—QT prolongation is a real and potentially fatal risk 3, 2
• Always check for drug interactions with CYP3A4 inhibitors and QT-prolonging medications 2, 5

Inappropriate combinations:

• Never combine with metoclopramide—they are alternatives, not complementary 1
• Avoid combining with other QT-prolonging drugs 3, 2