What are the guidelines for using domperidone (antiemetic medication) in pregnancy?

Domperidone Use in Pregnancy: Safety and Guidelines

Domperidone can be safely used during pregnancy as it has not been associated with increased risk of congenital malformations or adverse pregnancy outcomes. 1

Safety Profile in Pregnancy

First Trimester Exposure

• Multiple studies show no significant increase in major congenital malformations with domperidone use during the first trimester:
  • A large cohort study in the EFEMERIS database (13,964 pregnancies exposed to domperidone) found no increased risk of malformations (adjusted OR = 0.89 [0.77-1.03]) 2
  • A Japanese observational cohort study of 519 women exposed to domperidone in the first trimester showed no significant difference in major malformation rates compared to controls (adjusted OR: 1.86 [95%CI: 0.73-4.70]) 3
  • A prospective cohort study of 120 first-trimester exposures found similar fetal outcomes between domperidone-exposed and non-exposed pregnancies 4

Throughout Pregnancy

• The European Association for the Study of the Liver (EASL) guidelines explicitly list domperidone as compatible with all trimesters of pregnancy 1
• Domperidone is included in the EASL guidelines' table of medications compatible with pregnancy (first, second, and third trimesters) 1

Indications in Pregnancy

Domperidone is primarily used in pregnancy for:

1. Gastrointestinal disorders: Control of functional gastrointestinal disorders and symptoms 4
2. Hyperemesis gravidarum: Listed as a second-line treatment for hyperemesis gravidarum in clinical guidelines 1
3. Gastroesophageal reflux: Can increase lower esophageal sphincter tone, potentially reducing reflux symptoms in late pregnancy 5

Dosing Considerations

• Standard dosing in pregnancy is similar to non-pregnant adults
• Typical maximum dose used in pregnancy studies was 30 mg/day 4
• For gastroesophageal reflux, domperidone has been shown to increase lower esophageal sphincter pressure by 10-11 cm H₂O in pregnant women 5

Breastfeeding Considerations

• Domperidone is compatible with breastfeeding 1
• It is often used as a galactagogue to increase milk supply 1
• When taken orally, levels in breast milk are low due to first-pass hepatic and intestinal metabolism 1
• The relative infant dose is very low (0.01–0.35%) 1
• Women using domperidone while breastfeeding should have access to a breast pump if there is any delay in feeding their infant 1

Clinical Practice Points

• When prescribing domperidone in pregnancy, document the indication clearly
• Monitor for common side effects (headache, dry mouth, abdominal cramps)
• For hyperemesis gravidarum, consider domperidone as a second-line agent after first-line treatments (cyclizine, doxylamine/pyridoxine, prochlorperazine, or promethazine) have been tried 1
• Avoid high doses and prolonged use when possible, although no specific safety concerns have been identified

Potential Advantages Over Other Antiemetics

• Unlike ondansetron, which has been associated with a marginal increase in orofacial clefts and ventricular septal defects (though small absolute risk) 1, domperidone has not shown these associations
• Unlike metoclopramide, which crosses the blood-brain barrier more readily, domperidone has fewer central nervous system effects

Domperidone represents a safe option for treating nausea, vomiting, and gastrointestinal motility disorders during all stages of pregnancy with reassuring safety data from multiple observational studies.