What is the recommended treatment and dosage of domperidone (motility agent) for a patient with gastroparesis, considering potential side effects and patient demographics such as age, medical history, and impaired renal function?

Domperidone for Gastroparesis

Domperidone 10 mg three times daily is recommended as a third-line prokinetic agent for gastroparesis patients who have failed metoclopramide, though it requires FDA investigational new drug application for use in the United States. 1

Treatment Algorithm

When to Consider Domperidone

• Use domperidone only after failure of first-line metoclopramide (minimum 10 mg three times daily for at least 4 weeks) combined with dietary modifications (small particle size, low-fat diet for minimum 4 weeks). 2
• Consider domperidone particularly when symptoms include nausea, vomiting, postprandial fullness, and early satiety—the hallmark gastroparesis symptoms. 1
• Domperidone is especially useful for patients who cannot tolerate metoclopramide's central nervous system side effects, as domperidone has limited blood-brain barrier penetration. 1

Dosing Recommendations

Standard dosing is 10 mg three times daily before meals. 1, 3, 4

• Some protocols use 10 mg four times daily (QID), though this increases cardiovascular risk. 4, 5
• Do NOT escalate to 20 mg four times daily (80 mg/day total) due to cardiovascular safety concerns. 1
• In specialized centers with close cardiac monitoring, doses up to 120 mg/day have been used for refractory cases, though this requires frequent ECG surveillance. 6
• Average effective dose in clinical practice is 36 mg/day. 4

Expected Clinical Response

Symptom Improvement Timeline

• Symptom improvement typically begins by day 3 of treatment and is maintained throughout therapy. 3
• Formal assessment should occur at 2-3 months of treatment. 4
• Approximately 68-69% of patients experience symptom improvement, with 45% achieving at least moderate improvement. 1, 4

Specific Symptom Benefits

• Most effective for: postprandial fullness, nausea, vomiting, stomach fullness, and early satiety. 3, 4, 5
• Upper abdominal pain shows less consistent improvement. 3
• Reduces hospitalizations and improves quality of life in 88% of patients. 5
• Can accelerate gastric emptying from 87% retention at 2 hours to 57% retention (closer to normal). 5

Critical Safety Considerations

Cardiovascular Monitoring Requirements

All patients require baseline and periodic ECG monitoring due to QT prolongation risk. 1, 6

• Obtain baseline ECG before initiating therapy. 6
• Perform follow-up ECGs at regular intervals (FDA mandated for investigational use). 6
• QTc prolongation >450 ms (males) or >470 ms (females) is considered meaningful and requires dose reduction or discontinuation. 6
• In one study, 9.5% of patients on 120 mg/day developed asymptomatic meaningful QTc prolongation. 6
• One-third of patients may develop asymptomatic non-meaningful QTc prolongation. 6

Absolute Contraindications

• History of dangerous arrhythmias or prolonged QTc at baseline. 6
• Clinically significant electrolyte disturbances (must correct before initiating). 6
• Gastrointestinal hemorrhage or mechanical obstruction. 6
• Presence of prolactinoma. 6
• Pregnancy or breastfeeding. 6
• Known allergy to domperidone. 6

Common Side Effects

Side effects occur in approximately 38% of patients, with 12% requiring discontinuation. 4

Most common adverse effects include:

• Headache (most frequent). 4
• Tachycardia/palpitations (19% report palpitations or chest pain, though often without ECG abnormalities). 4, 6
• Diarrhea. 4
• Breast tenderness and gynecomastia (due to prolactin elevation; mean prolactin level 58.9 pg/ml). 5
• Menstrual irregularities. 3
• Dizziness, drowsiness, constipation (less common). 3

Drug-Drug Interactions

• Domperidone is metabolized via cytochrome P450 pathways, creating potential for interactions with other gastroparesis medications. 7
• Exercise caution when combining with other QT-prolonging agents (e.g., ondansetron, which is commonly used as second-line antiemetic). 2, 7
• Monitor for interactions with antidiabetic agents in diabetic gastroparesis patients. 7

Special Population Considerations

Renal Impairment

• While specific renal dosing adjustments are not detailed in the guidelines, domperidone undergoes hepatic metabolism, making it potentially safer than renally-cleared alternatives in renal dysfunction. 7
• However, close monitoring remains essential given cardiovascular risks.

Long-Term Use

• Domperidone has been used safely for extended periods (average 23-52 months in studies) with appropriate monitoring. 5, 6
• Long-term efficacy is maintained without significant tachyphylaxis. 5
• Extrapyramidal side effects are less frequent than with metoclopramide, even with chronic use. 1

Regulatory Barriers

A major limitation is that domperidone requires an FDA investigational new drug application for use in the United States, restricting its availability. 1

• This administrative burden limits widespread use despite clinical efficacy. 1
• Patients and providers must navigate the IND application process. 4