What is the recommended use and dosage of Domperidone for a patient with severe nausea and vomiting, particularly in those with gastrointestinal disorders or undergoing chemotherapy?

Domperidone for Severe Nausea and Vomiting

Domperidone is an effective dopamine D2-receptor antagonist for managing severe nausea and vomiting in gastroparesis and chemotherapy-induced symptoms, with the recommended starting dose being 10 mg three times daily, though availability in the United States requires FDA investigational drug application. 1

Recommended Dosing

Standard Dosing Protocol

• Start with 10 mg orally three times daily before meals 1
• The pediatric dose is 0.7 mg/kg per dose for chemotherapy-induced nausea 2
• Although escalation to 20 mg four times daily has been reported, this should be avoided due to cardiovascular safety concerns, particularly QT prolongation risk 1
• For chemotherapy patients, administer 20 mg three to four times daily 1

Clinical Context for Use

Gastroparesis Management:

• Domperidone is appropriate when metoclopramide fails or causes intolerable central nervous system side effects 1
• In a prospective study of 34 gastroparesis patients, 68% showed improvement in symptom scores with domperidone 10 mg three times daily 1, 3
• Symptom improvement occurs as early as day 3 of treatment, with sustained benefit throughout the treatment course 3
• Domperidone specifically improves early satiety, postprandial fullness, and overall gastroparesis symptom severity 3

Chemotherapy-Induced Nausea and Vomiting:

• Domperidone is recommended as an add-on agent for breakthrough symptoms rather than first-line therapy 1, 4
• For delayed nausea and vomiting after highly emetogenic chemotherapy, domperidone 20 mg three times daily is more effective than ondansetron 8 mg three times daily 5
• Domperidone demonstrates comparable efficacy to chlorpromazine but with significantly fewer side effects 6

Critical Safety Considerations

Cardiovascular Risks

• QT prolongation and ventricular tachycardia are documented risks 1
• In the gastroparesis cohort study, 7% of patients experienced cardiac side effects requiring drug cessation 1
• The risk of QT prolongation with usual therapeutic oral doses appears low, but intravenous bolus doses carry higher risk 1
• Avoid doses exceeding 10 mg three times daily to minimize cardiovascular complications 1

Advantages Over Alternatives

• Domperidone does not readily cross the blood-brain barrier, resulting in fewer central nervous system side effects compared to metoclopramide 1
• No extrapyramidal symptoms or tardive dyskinesia risk, unlike metoclopramide which carries an FDA boxed warning 1, 7
• Side effects reported include palpitations, headache, breast tenderness, menstrual bleeding, dizziness, drowsiness, chest pain, and constipation 3

Treatment Algorithm

For Gastroparesis:

1. First-line: Metoclopramide 10 mg three times daily before meals 7
2. If metoclopramide fails or causes CNS side effects: Switch to domperidone 10 mg three times daily 1
3. If domperidone alone insufficient: Add 5-HT3 antagonist (ondansetron 8 mg twice daily or granisetron 2 mg daily) rather than increasing domperidone dose 1, 8

For Chemotherapy-Induced Nausea:

1. First-line prevention: Triple therapy with NK-1 antagonist (aprepitant), 5-HT3 antagonist (granisetron), and dexamethasone 4
2. For breakthrough symptoms: Add domperidone 20 mg three to four times daily to existing regimen 1, 4
3. For delayed emesis: Domperidone 20 mg three times daily is superior to ondansetron for prevention 5

Common Pitfalls to Avoid

• Do not escalate to 20 mg four times daily due to increased cardiovascular risk without proportional benefit 1
• Do not use as monotherapy for highly emetogenic chemotherapy where triple therapy is indicated 4
• Ensure adequate dilution for intravenous administration to prevent pain at injection site 2
• Screen for cardiac risk factors before initiating therapy, particularly in patients with baseline QT prolongation 1
• Remember U.S. availability restrictions: Domperidone requires FDA investigational drug application and is not routinely available 1