Metoclopramide (Reglan) in Pregnancy
Metoclopramide is safe and effective for treating nausea and vomiting in pregnancy, including hyperemesis gravidarum, with extensive evidence showing no increased risk of major congenital malformations, spontaneous abortion, or stillbirth. 1
Treatment Algorithm Position
- Metoclopramide serves as second-line therapy after vitamin B6 (pyridoxine) fails to control symptoms, per American Gastroenterological Association guidelines 1
- First-line treatment remains doxylamine-pyridoxine combination 2
- Metoclopramide is preferred over ondansetron before 10 weeks gestation, as ondansetron carries small absolute risk increases for orofacial clefts (0.03%) and ventricular septal defects (0.3%) 1
- Reserve corticosteroids (methylprednisolone) as last resort for severe hyperemesis, and avoid entirely before 10 weeks gestation due to cleft palate risk 1
Safety Evidence
The safety profile is robust with over 33,000 first-trimester exposures documented:
- A Danish cohort of 28,486 first-trimester exposures showed no association with major malformations (prevalence odds ratio 0.93,95% CI 0.86-1.02) 3
- Meta-analysis of six cohort studies with 33,000 exposed women found no increased risk of major congenital defects (odds ratio 1.14,99% CI 0.93-1.38) 1
- Israeli cohort of 3,458 first-trimester exposures demonstrated no increased risks of major malformations (5.3% vs 4.9% unexposed), low birth weight, preterm delivery, or perinatal death 4
- No association with spontaneous abortion (HR 0.35,95% CI 0.33-0.38) or stillbirth (HR 0.90,95% CI 0.74-1.08) 3
Recommended Dosing
Standard dosing: 5-10 mg orally every 6-8 hours as needed 1
Critical Safety Warning
Discontinue metoclopramide immediately if extrapyramidal symptoms develop (dystonia, akathisia, parkinsonism) 1
- Extrapyramidal reactions typically occur within first 2 days of treatment 1
- Higher risk in patients under age 30 1
- In comparative studies with promethazine for hospitalized hyperemesis patients, metoclopramide caused less drowsiness, dizziness, and dystonia despite similar efficacy 1
Comparative Efficacy
- Metoclopramide and promethazine show similar efficacy for hyperemesis gravidarum, but metoclopramide has fewer side effects including less drowsiness, dizziness, dystonia, and fewer treatment discontinuations 1
- Can be safely combined with vitamin B6 and vitamin B1 (thiamine) supplementation 1
Important Clinical Context
A 2022 Norwegian study revealed concerning consequences when the 2013 European Medical Agency warning restricted metoclopramide use to 5 days maximum: pre-hospital antiemetic use dropped 20%, women presented for hospitalization 3.8 days earlier in gestation, and termination of pregnancy rates increased by 4.8% 5. This underscores the importance of adequate antiemetic treatment for maternal and fetal wellbeing.