What are safe prokinetic agents (gastrokinetic agents) in pregnancy?

From the Guidelines

Metoclopramide is the safest prokinetic medication to use during pregnancy, particularly for managing nausea, vomiting, and gastroesophageal reflux disease. The typical dosage is 5-10 mg orally three to four times daily, with treatment generally limited to 12 weeks or less to minimize the risk of tardive dyskinesia. Metoclopramide has been extensively studied in pregnancy with no evidence of increased birth defects or adverse pregnancy outcomes, as supported by the strong consensus in the ESPEN guideline on clinical nutrition in the intensive care unit 1. It works by blocking dopamine receptors in the chemoreceptor trigger zone and enhancing gastric emptying. For women with more severe symptoms, domperidone (10 mg orally three times daily) may be considered as a second-line option, though it has less pregnancy safety data than metoclopramide. Erythromycin at low doses (250 mg two to three times daily) can also be used short-term for gastroparesis in pregnancy. Avoid newer prokinetics like prucalopride, as they lack sufficient pregnancy safety data.

Some key points to consider when using prokinetics in pregnancy include:

• Starting with the lowest effective dose and discontinuing as soon as symptoms resolve
• Using non-pharmacological approaches like small frequent meals, avoiding trigger foods, and elevating the head of the bed before or alongside medication therapy
• Limiting the use of metoclopramide to 12 weeks or less to minimize the risk of tardive dyskinesia
• Considering domperidone or erythromycin as alternative options for women with more severe symptoms or those who do not respond to metoclopramide

It's also important to note that the AGA clinical practice update on pregnancy-related gastrointestinal and liver disease provides guidance on the management of gastrointestinal symptoms during pregnancy, but does not specifically address the use of prokinetics 1. However, the ESPEN guideline provides a strong consensus on the use of metoclopramide as a prokinetic therapy, which supports its safety and efficacy in pregnancy 1. An older study on the management of cough in adults also mentions the use of prokinetic agents like metoclopramide, but this is not directly relevant to the use of prokinetics in pregnancy 1.

From the FDA Drug Label

Pregnancy 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.

Safe use of metoclopramide in pregnancy is not fully established due to the lack of adequate and well-controlled studies in pregnant women.

• Although animal studies have shown no significant harm to the fetus,
• the drug should be used during pregnancy only if clearly needed 2.

From the Research

Safe Prokinetics in Pregnancy

• The use of prokinetics during pregnancy is a topic of interest, with various studies examining their safety and efficacy 3, 4, 5.
• Metoclopramide is a commonly used prokinetic agent, and studies have shown that it is not associated with significantly increased risks of major congenital malformations, low birth weight, preterm delivery, or perinatal death when used during the first trimester of pregnancy 4, 5.
• A systematic review and meta-analysis found that metoclopramide use during the first trimester of pregnancy was not associated with the risk of major congenital malformations, with an odds ratio of 1.14 (95% CI, 0.93-1.38) 5.
• Another study found that combined metoclopramide-continuous low-dose erythromycin was the best protocol to increase gastric emptying rate in ventilated patients, although this study was not specifically focused on pregnancy 6.
• The safety of other prokinetic agents, such as cisapride, has not been extensively studied in pregnancy, and their use is generally not recommended due to potential risks to the fetus 3.

Prokinetic Agents in Pregnancy

• Metoclopramide is considered a safe and effective prokinetic agent for use during pregnancy, particularly during the first trimester 4, 5.
• The use of other prokinetic agents, such as erythromycin, may be considered in certain situations, although more research is needed to fully understand their safety and efficacy in pregnancy 6.
• Proton pump inhibitors, which are sometimes used in conjunction with prokinetic agents, are not recommended during pregnancy except in severe cases of gastroesophageal reflux or prior to anesthesia during labor and delivery 3.