What is the recommended dosage and treatment plan for domperidone (motility agent) in patients with gastroparesis?

Domperidone Dosage and Treatment Plan for Gastroparesis

The recommended dosage for domperidone in gastroparesis is 10 mg three times daily before meals, with careful monitoring for cardiac side effects, as higher doses increase the risk of QT prolongation and ventricular tachycardia. 1

Dosing Recommendations

• Starting dose: 10 mg three times daily (30 minutes before meals)
• Maximum recommended dose: 10 mg three times daily (30 mg/day)
• Duration: Long-term therapy may be beneficial, with studies showing efficacy over an average of 23.3 months 2
• Availability in the US: Only through FDA investigational drug application 1

Monitoring Requirements

• Baseline ECG: Required before initiating therapy to assess QT interval
• Follow-up ECGs: Recommended periodically during treatment
• Symptom assessment: Evaluate response at 2-3 months using standardized tools like GCSI (Gastroparesis Cardinal Symptom Index)
• Side effect monitoring: Particularly for cardiac effects, headache, and hormonal changes

Efficacy Timeline and Expected Benefits

Domperidone typically begins showing efficacy early in treatment:

• Improvement in overall gastroparesis symptoms can be observed as early as day 3 of treatment 3
• Significant improvements in early satiety, postprandial fullness, and overall symptom severity occur within the first few weeks 3
• Studies show 68-69% of patients report symptom improvement 4

Side Effects to Monitor

• Cardiac: Palpitations/tachycardia (reported in 7% of patients) 1, 4
• Hormonal: Gynecomastia, menstrual irregularities, elevated prolactin levels 4, 2
• Neurological: Headache, dizziness 4
• Gastrointestinal: Diarrhea 4

Important Cautions

• QT prolongation risk: Although escalation to 20 mg four times daily has been reported in some studies, this should be avoided due to cardiovascular safety concerns 1
• Drug interactions: Domperidone is metabolized by CYP3A4, so concomitant use with CYP3A4 inhibitors should be avoided to prevent increased domperidone levels and potential cardiac toxicity 5
• Discontinuation rate: Approximately 12% of patients discontinue treatment due to side effects 4

Treatment Algorithm

1. Confirm diagnosis of gastroparesis with gastric emptying scintigraphy
2. Initiate dietary modifications (small, frequent meals; low-fat, low-fiber diet)
3. Start domperidone at 10 mg TID before meals if:
   • Patient has failed metoclopramide OR
   • Patient has intolerable side effects from metoclopramide OR
   • Patient has contraindications to metoclopramide
4. Evaluate response after 2-3 months:
   • If good response with minimal side effects: continue therapy
   • If inadequate response: consider adjunctive therapies rather than dose escalation
   • If intolerable side effects: discontinue and consider alternative agents

Alternative Treatments When Domperidone Fails

If domperidone is ineffective or poorly tolerated, consider:

• 5-HT3 receptor antagonists (ondansetron 4-8 mg BID/TID, granisetron 1 mg BID) 1
• NK-1 receptor antagonists (aprepitant 80 mg/day) 1, 6
• Phenothiazine antipsychotics (prochlorperazine 5-10 mg QID) 1

For severe, refractory cases, interventional therapies may be considered:

• Gastric electrical stimulation 6
• Gastric peroral endoscopic myotomy (G-POEM) 6

By following this structured approach to domperidone therapy for gastroparesis, clinicians can maximize benefits while minimizing risks, potentially improving quality of life and reducing hospitalizations for patients with this challenging condition.