Metoclopramide Safety in Pregnancy
Metoclopramide is safe to use during pregnancy and can be used as a first-line or second-line antiemetic for nausea and vomiting, with no increased risk of major congenital malformations, spontaneous abortion, or stillbirth. 1, 2
Evidence for Safety
The safety profile of metoclopramide in pregnancy is well-established through large-scale studies:
A meta-analysis of six cohort studies including 33,000 first-trimester exposed women and over 37,000 controls found no significant increased risk of major congenital defects (odds ratio 1.14,99% CI 0.93-1.38). 2, 3
The largest single cohort study from Denmark (2013) evaluated 28,486 women exposed to metoclopramide in the first trimester and found no association with major malformations overall (prevalence odds ratio 0.93,95% CI 0.86-1.02), spontaneous abortion (HR 0.35,95% CI 0.33-0.38), or stillbirth (HR 0.90,95% CI 0.74-1.08). 4
This Danish study specifically examined 20 individual malformation categories and found no increased risk for any of them, including neural tube defects, cardiac defects, cleft lip/palate, and limb reduction defects. 4
Clinical Positioning in Treatment Algorithms
For Nausea and Vomiting of Pregnancy (NVP) and Hyperemesis Gravidarum (HG):
Metoclopramide can be used as either first-line or second-line therapy depending on the guideline consulted:
The 2024 AGA guidelines recommend metoclopramide as part of a step-up approach for patients not responding to first-line vitamin B6 therapy. 1
European guidelines position metoclopramide as second-line therapy after doxylamine/pyridoxine and phenothiazines. 1
However, other guidelines consider metoclopramide appropriate for first-line use. 2
In a randomized trial comparing metoclopramide to promethazine for hospitalized HG patients, both had similar efficacy, but metoclopramide had significantly fewer side effects including less drowsiness, dizziness, dystonia, and fewer discontinuations due to adverse events. 1
For Migraine-Associated Nausea in Pregnancy:
- Metoclopramide can be used for nausea associated with migraine during pregnancy. 1
Dosing:
- Standard dosing is 5-10 mg orally every 6-8 hours as needed. 2
- Treatment duration should not exceed 12 weeks due to risk of tardive dyskinesia. 5
Important Safety Considerations and Caveats
Maternal Side Effects to Monitor:
Extrapyramidal symptoms can occur with metoclopramide use: 1, 5
Dystonia (uncontrolled muscle spasms) typically occurs within the first 2 days of treatment and is more common in patients under age 30. 5
Tardive dyskinesia risk increases with duration of use beyond 12 weeks and cumulative dose—this is why the 12-week maximum is critical. 5
If extrapyramidal symptoms develop, the drug should be withdrawn immediately. 1
Comparative Safety with Alternative Antiemetics:
Ondansetron considerations: 2
- Also considered safe during pregnancy but has been associated with small absolute risk increases of orofacial clefts (0.03%) and ventricular septal defects (0.3%) when used in early pregnancy. 2
- The 2024 AGA guidelines recommend ondansetron primarily for severe NVP requiring hospitalization and suggest using it on a case-by-case basis before 10 weeks gestation. 1
Corticosteroids (methylprednisolone): 1, 2
- Reserved as last resort for severe HG. 1
- Should be avoided before 10 weeks gestation due to potential increased risk of cleft palate. 1, 2
Supportive Care Context:
- Metoclopramide may be safely combined with other supportive measures including vitamin B6 (pyridoxine) and vitamin B1 (thiamine) supplementation. 1
- Corticosteroids should be omitted in the first trimester when using antiemetics. 1