What are the recommended adult dose, contraindications, and safety precautions for domperidone, including considerations for the elderly and children?

Domperidone: Dosing, Contraindications, and Safety

Adult Dosing

The recommended starting dose of domperidone for adults is 10 mg orally three times daily (total 30 mg/day), with escalation to 20 mg three to four times daily (60-80 mg/day) possible but generally avoided due to cardiovascular safety concerns. 1, 2

• The American Gastroenterological Association specifically recommends starting at 10 mg three times daily for gastroparesis and nausea, with the caveat that doses above 10 mg three times daily should be avoided when possible to minimize cardiac risks 1, 3
• Although escalation to 20 mg four times daily (80 mg/day) has been reported in clinical practice, this higher dosing should be reserved for refractory cases due to increased risk of QT prolongation and ventricular tachycardia 1
• The European Medicines Agency explicitly recommends against long-term use and emphasizes maintaining the lowest effective dose with regular cardiac monitoring if extended therapy is necessary 3

Pediatric and Adolescent Dosing

For children and adolescents aged 12-17 years, domperidone can be used for nausea at standard pediatric dosing of 0.2 mg/kg three times daily (0.6 mg/kg/day total), though oral administration is unlikely to prevent vomiting. 1, 3

• The American Academy of Pediatrics provides an alternative dosing regimen of 2 mg/kg/day divided into four daily doses 3
• Domperidone use in children is largely off-label, with limited evidence for efficacy in pediatric gastrointestinal motility disorders 4
• For adolescents with migraine-associated nausea, domperidone is an option though evidence in this age group remains limited 1

Elderly Patients

Domperidone should be avoided in patients over 60 years old when possible, as this population has a 2.8-fold increased odds ratio for sudden cardiac death. 3

• If domperidone must be used in elderly patients, the lowest effective dose (preferably 10 mg three times daily) should be maintained with mandatory baseline and periodic ECG monitoring 3
• Elderly patients require more cautious dose selection and closer cardiovascular monitoring due to age-related changes in cardiac conduction and higher prevalence of cardiovascular comorbidities 3

Absolute Contraindications

Domperidone is contraindicated in patients with pre-existing QT prolongation/Long QT Syndrome, those receiving CYP3A4 inhibitors, patients with electrolyte abnormalities, and those with other risk factors for QT prolongation. 5

• Concurrent use with medications that inhibit CYP3A4 (such as azole antifungals, macrolide antibiotics, protease inhibitors) is contraindicated due to increased domperidone plasma levels and cardiac risk 5
• Patients with uncorrected hypokalemia, hypomagnesemia, or hypocalcemia should not receive domperidone until electrolyte abnormalities are corrected 5
• Pre-existing cardiac conduction disorders or structural heart disease represent relative contraindications requiring specialist consultation 5

Cardiovascular Safety Monitoring

Baseline ECG with QTc interval assessment is mandatory before initiating domperidone, particularly in patients over 60 years old, those with cardiac risk factors, or when doses exceed 30 mg/day. 2, 3

• The National Patient Safety Agency requires periodic ECG monitoring during therapy to assess for QTc prolongation 3
• The European Society of Cardiology specifically recommends ECG screening for all patients over 60 years old or those receiving doses above 30 mg/day 2
• QT prolongation and torsade de pointes tachycardia are the primary cardiac risks, particularly with intravenous administration 2

Clinical Efficacy and Indications

Domperidone demonstrates modest efficacy for gastroparesis symptoms, with a single-center cohort study showing 68% of patients (n=115) had improvement in symptom scores, though 7% experienced cardiac side effects requiring drug cessation. 1

• Domperidone is effective for symptoms of diabetic gastropathy including anorexia, nausea, vomiting, abdominal pain, early satiety, bloating, and distension 6, 7
• For functional dyspepsia with predominant fullness, bloating, or early satiety (dysmotility-like symptoms), domperidone is the appropriate first-line prokinetic option 2
• In chemotherapy-induced nausea and vomiting, domperidone 20 mg three to four times daily can be added to standard antiemetic regimens for refractory cases 2
• Symptomatic improvement with domperidone 80 mg/day is similar to cisapride 40 mg/day or metoclopramide 40 mg/day, with therapeutic benefits maintained for up to 12 years in some studies 7

Advantages Over Metoclopramide

Domperidone has significantly fewer central nervous system side effects than metoclopramide because it does not readily cross the blood-brain barrier, making it the preferred option for long-term therapy despite cardiovascular concerns. 1, 2

• Extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) are rare with domperidone compared to metoclopramide, which carries FDA restrictions limiting use beyond 12 weeks 2
• The American Gastroenterological Association recommends domperidone as an alternative to metoclopramide for extended therapy due to its lower neurological risk profile 2
• Domperidone 40-80 mg/day may be effective in patients refractory to metoclopramide, with better tolerability regarding extrapyramidal side effects 3, 7

Critical Safety Pitfall: Combination Therapy

Never combine domperidone with metoclopramide—they are alternative treatments, not complementary therapies, as both are dopamine D2-receptor antagonists with overlapping mechanisms and additive risks without demonstrated additional benefit. 2

• The American Diabetes Association guidelines list these agents as alternatives, not complementary therapies 2
• If domperidone fails, switch to metoclopramide (or vice versa), do not add the second agent 2
• Combining these agents increases both cardiovascular risk (from domperidone) and extrapyramidal risk (from metoclopramide) without improving efficacy 2

Special Populations: Pregnancy and Breastfeeding

For pregnant women with migraine-associated nausea, metoclopramide (not domperidone) is the recommended antiemetic under specialist supervision. 1

• Domperidone has a milk:plasma ratio of 0.25 and relative infant dose of 0.01-0.35%, making it one of the safer antiemetic options during lactation from a pharmacokinetic perspective 2
• However, more safety information is required regarding risk to breastfeeding infants before domperidone is routinely recommended in this population 5
• When used as a galactogogue in healthy breastfeeding women, domperidone may be used without direct risk to the mother if cardiovascular contraindications are excluded, though this remains an off-label indication 5

Availability and Regulatory Status

In the United States, domperidone is only available through an FDA investigational drug application and is not commercially marketed, whereas it is widely available in Canada and many other countries. 1, 2

• Metoclopramide remains the only FDA-approved drug for gastroparesis in the United States 2
• The 10 mg tablet formulation is the only dosage form available in Canada and under investigation in the US 6

Duration of Action and Dosing Frequency

Domperidone has a duration of effect of 7-14 hours with a plasma half-life of approximately 7.5 hours, supporting three to four times daily dosing. 2

• The elimination half-life ranges from 7.5 to 16 hours, with most guidelines citing a duration of antiemetic action of 7-14 hours per dose 2
• This pharmacokinetic profile supports the standard three times daily dosing regimen for most indications 2

Treatment Duration and Response Assessment

An initial trial of 2-4 weeks of empirical therapy with domperidone is recommended, with consideration for trial withdrawal if symptoms improve to assess whether continued therapy is necessary. 2

• If symptoms improve, consider discontinuing therapy and resuming only if symptoms recur 2
• The British Society of Gastroenterology explicitly states that domperidone should no longer be used long-term for chronic gastrointestinal motility disorders due to cumulative cardiac risks 2
• For short-term use in acute settings, domperidone provides relief within days, but long-term efficacy must be balanced against cardiovascular risk 2