What are the effects of Metoclopramide (MET) on pregnancy?

From the Guidelines

Metoclopramide can be safely used during pregnancy for treating nausea and vomiting, with a recommended dosage of 5-10 mg orally every 6-8 hours, as it has not been shown to significantly increase the risk of major congenital defects 1. The use of metoclopramide in pregnancy is supported by a meta-analysis of six cohort studies, which found no significant increase in the risk of major congenital defects with its use 1. Key considerations for its use include:

• Starting with a lower dose of 5 mg and titrating up to 10 mg as needed
• Limiting treatment duration to the shortest time necessary, ideally less than 12 weeks
• Monitoring for potential side effects, such as extrapyramidal symptoms, drowsiness, and restlessness
• Weighing the benefits of treatment against the potential risks, particularly in cases of severe nausea and vomiting that can lead to dehydration, electrolyte imbalances, and poor maternal nutrition. According to the most recent study 1, metoclopramide can be given for NVP and HG, and has similar efficacy to promethazine, but with fewer adverse events. It is essential to consider first-line treatments like dietary modifications, ginger, vitamin B6, and antihistamines before starting metoclopramide 1. The American College of Gastroenterology recommends a step-up approach for patients who do not respond to first-line therapy, with metoclopramide as a potential second-line treatment 1. Overall, metoclopramide can be a safe and effective treatment option for nausea and vomiting during pregnancy, when used judiciously and with careful consideration of the potential benefits and risks 1.

From the FDA Drug Label

Reproduction studies performed in rats, mice, and rabbits by the IM, IV, subcutaneous (SC), and oral routes at maximum levels ranging from 12 to 250 times the human dose have demonstrated no impairment of fertility or significant harm to the fetus due to metoclopramide. There are, however, no adequate and well-controlled studies in pregnant women Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

you are pregnant or plan to become pregnant. It is not known if metoclopramide will harm your unborn child.

Metoclopramide use in pregnancy should be approached with caution. While animal studies have shown no significant harm to the fetus, there are no adequate and well-controlled studies in pregnant women. Therefore, metoclopramide should only be used during pregnancy if clearly needed 2. It is essential to weigh the potential benefits against the potential risks, and pregnant women should be closely monitored by their healthcare provider. The safety of metoclopramide in human pregnancy has not been established 2.

From the Research

Metoclopramide Use in Pregnancy

• Metoclopramide is a drug frequently used for nausea and vomiting in pregnancy, and studies have investigated its safety in this context 3, 4, 5, 6, 7.
• A study published in JAMA in 2013 found that metoclopramide use in the first trimester was not associated with an increased risk of major congenital malformations, spontaneous abortion, or stillbirth 3.
• Another study published in The New England Journal of Medicine in 2009 also found that metoclopramide use during the first trimester was not associated with significantly increased risks of major congenital malformations, low birth weight, preterm delivery, or perinatal death 5.
• A systematic review and meta-analysis published in PloS one in 2021 found that metoclopramide use during the first trimester was not associated with an increased risk of major congenital malformations 7.
• A study published in Expert opinion on drug safety in 2017 noted that the fetal safety of metoclopramide has been documented, and it is considered a safe option for treating nausea and vomiting in pregnancy 4.
• A systematic review published in JAMA in 2016 found that metoclopramide was associated with improved symptoms of nausea and vomiting in pregnancy, particularly for mild symptoms 6.

Safety Considerations

• The studies suggest that metoclopramide is a safe option for treating nausea and vomiting in pregnancy, with no significant increase in the risk of major congenital malformations or other adverse outcomes 3, 5, 7.
• However, it is essential to consider the individual patient's needs and medical history when prescribing metoclopramide or any other medication during pregnancy 4, 6.
• More research is needed to fully understand the safety and efficacy of metoclopramide and other treatments for nausea and vomiting in pregnancy, particularly for severe cases 6.