Is domperidone appropriate for a pregnant patient with severe nausea/vomiting, and what are the risks, dosing, and monitoring recommendations?

Domperidone Use in Pregnancy

Domperidone is an acceptable second-line antiemetic for severe nausea and vomiting in pregnancy, including the first trimester, with reassuring safety data showing no increased risk of congenital malformations. 1, 2

Evidence-Based Safety Profile

The European Association for the Study of the Liver (EASL) explicitly classifies domperidone as compatible with all trimesters of pregnancy, including first trimester use, for management of hyperemesis gravidarum. 1, 2 This represents the highest-quality guideline recommendation available.

Large-scale safety data are reassuring:

• A retrospective cohort study of 13,964 pregnancies exposed to domperidone (>75% in first trimester) found no increased malformation rate compared to unexposed pregnancies (adjusted OR = 0.89 [0.77-1.03]). 3
• A prospective cohort of 120 first-trimester exposures showed similar rates of major malformations between exposed and unexposed groups (OR = 0.6; 95% CI 0.1,2.8). 4

Treatment Algorithm for Nausea/Vomiting in Pregnancy

First-line therapy (start here): 5

• Non-pharmacologic: Small, frequent bland meals; ginger 250 mg four times daily 5
• Pharmacologic: Vitamin B6 (pyridoxine) 10-25 mg every 8 hours, or doxylamine-pyridoxine combination 10-20 mg 5

Second-line therapy (if first-line fails): 1, 2

• Metoclopramide is preferred due to more extensive safety data (33,000 first-trimester exposures, OR 1.14,99% CI 0.93-1.38 for malformations) 1
• Domperidone is an acceptable alternative with comparable safety profile 1, 2
• Phenothiazines (prochlorperazine, promethazine) are also options 6

Third-line therapy (severe/refractory cases): 5

• Ondansetron (use cautiously before 10 weeks due to potential cardiac defect association) 2
• Intravenous glucocorticoids for hospitalized patients 5

Dosing and Monitoring Recommendations

Domperidone dosing:

• Maximum dose: 30 mg/day in divided doses 4
• Duration: Typically used between 2-20 weeks gestation 4

Critical monitoring parameters:

• Cardiac considerations: Domperidone causes hERG channel inhibition and QT prolongation at clinically relevant concentrations. 7, 8
• Contraindications: Pre-existing QT prolongation/LQTS, concurrent CYP3A4 inhibitors, electrolyte abnormalities 7
• Monitor for extrapyramidal symptoms and discontinue if they develop 2

Essential supportive care:

• Thiamine supplementation 100 mg daily for minimum 7 days in prolonged vomiting to prevent Wernicke encephalopathy 1
• Use PUQE score to quantify severity and guide treatment intensity 1
• Correct electrolyte abnormalities and ensure adequate hydration 9

Key Clinical Pitfalls to Avoid

Do not delay escalation of therapy when first-line treatments fail, as this can lead to progression to hyperemesis gravidarum (affects 0.3-2% of pregnancies). 1, 5 Early intervention is crucial.

Do not use domperidone in patients with:

• Known cardiac conduction abnormalities or QT prolongation 7
• Concurrent medications that inhibit CYP3A4 (increases domperidone exposure) 7
• Electrolyte disturbances (correct first) 7

Important regulatory note: Domperidone is not FDA-approved for any indication in the United States, though it is widely used internationally. 10 The FDA label specifically warns against human use, though this refers to a veterinary formulation. 10

Breastfeeding Considerations

While EASL guidelines classify domperidone as compatible with breastfeeding 1, the American Gastroenterological Association notes that more safety information is needed regarding risk to breastfeeding infants before routine use. 7 Pregnant and lactating women should use caution when handling domperidone as systemic exposure may affect reproductive hormones. 10