What is the comparative efficacy of metoclopramide (Metoclopramide) versus ondansetron (Ondansetron) for treating morning sickness (Hyperemesis gravidarum) in the first trimester of pregnancy?

From the Guidelines

For first trimester morning sickness, metoclopramide is generally considered a safer option compared to ondansetron due to the potential increased risk of oral clefts associated with ondansetron use in the first trimester, as noted in the European Association for the Study of the Liver Clinical Practice Guidelines 1.

Key Considerations

• Both metoclopramide and ondansetron are considered second-line treatments after initial measures fail, according to the American College of Obstetricians and Gynecologists (ACOG) recommendations 1.
• Metoclopramide is typically prescribed as 10mg orally three to four times daily, while ondansetron is usually prescribed as 4-8mg orally every 8 hours as needed.
• Lifestyle modifications should be attempted first, including eating small, frequent meals, avoiding triggers, consuming ginger (250mg four times daily), and taking vitamin B6 (10-25mg three times daily), possibly combined with doxylamine (12.5mg three to four times daily) 1.
• Metoclopramide works by blocking dopamine receptors and stimulating upper GI motility, while ondansetron blocks serotonin receptors in the brain and gut.
• The European Association for the Study of the Liver Clinical Practice Guidelines recommend doxylamine and pyridoxine as first-line pharmacologic treatment of Hyperemesis Gravidarum, with metoclopramide and ondansetron as second-line therapies 1.

Potential Risks and Side Effects

• Ondansetron use in pregnancy has been associated with an increased rate of orofacial clefting, although the absolute risk is still relatively low, increasing from 11 cases per 10,000 births to 14 cases per 10,000 births 1.
• Metoclopramide may cause more maternal side effects, including drowsiness and extrapyramidal symptoms, as noted in the ACOG recommendations 1.
• Drug-induced extrapyramidal symptoms and oculogyric crises can occur with the use of phenothiazines and metoclopramide, and patients reporting relevant symptoms should have the drug withdrawn and appropriate treatment initiated 1.

From the Research

Comparative Efficacy of Metoclopramide and Ondansetron

• The efficacy of metoclopramide versus ondansetron for treating morning sickness in the first trimester of pregnancy is compared in several studies 2, 3, 4, 5, 6.
• Ondansetron has been shown to be an effective treatment for nausea and vomiting, including pregnancy-related morning sickness 2.
• Metoclopramide is also safe and effective, and can be used alone or in combination with other antiemetics 3.
• A survey of prescribing practices in Australasia found that metoclopramide is commonly used as a first-line choice for morning sickness, while ondansetron is often prescribed for hyperemesis gravidarum 4.
• Studies have investigated the safety of metoclopramide use during the first trimester of pregnancy, and found no significant increase in the risk of major congenital malformations 5, 6.

Safety and Efficacy

• Ondansetron has been found to be safe and effective for use in pregnant women, with a small increase in the absolute risk of orofacial clefting 3.
• Metoclopramide has also been found to be safe for use in pregnancy, with no significant increase in the risk of major congenital malformations 5, 6.
• The use of metoclopramide and ondansetron as second-line antiemetics is recommended if first-line antiemetics are ineffective 3.

Clinical Guidelines

• Clinical guidelines recommend the use of antiemetics such as metoclopramide and ondansetron for the management of nausea and vomiting in pregnancy 3.
• The guidelines also recommend that women be asked about previous adverse reactions to antiemetic therapies, and that prompt cessation of medications occur if adverse reactions occur 3.