Which is safer in pregnancy, Emeset (Ondansetron) or Perinorm (Metoclopramide)?

Metoclopramide (Perinorm) is safer in pregnancy than Ondansetron (Emeset)

Metoclopramide should be the preferred antiemetic in pregnancy, particularly during the first trimester, as it has extensive safety data without teratogenic concerns, while ondansetron carries a small but documented increased risk of orofacial clefts. 1, 2

First-Line Treatment Approach

• Metoclopramide is recommended as a safe and effective antiemetic that can be used throughout pregnancy 1
• Multiple international guidelines specifically endorse metoclopramide for nausea in pregnant women, including those with cancer, migraine, and liver disease 1
• Metoclopramide has large studies documenting fetal safety with no evidence of teratogenicity 3

The Ondansetron Controversy

• Ondansetron use in the first trimester increases the absolute risk of orofacial clefts from 11 cases per 10,000 births to 14 cases per 10,000 births 1
• This represents a very small absolute risk increase, but it is a documented and reproducible finding 1, 2
• The European Medicines Agency now states ondansetron should not be used during the first trimester based on concerns about orofacial clefts and congenital heart defects 4
• Some large studies are reassuring about ondansetron safety, but they are contrasted by studies claiming increased teratogenicity 3

When to Consider Ondansetron

• Ondansetron should be reserved as second-line therapy when first-line antiemetics (including metoclopramide) are ineffective 2
• Women can be counseled about the very small absolute risk increase in orofacial clefting, which should be balanced against the risks of poorly managed hyperemesis gravidarum 2
• In severe vomiting unresponsive to metoclopramide, ondansetron demonstrated superior control of vomiting (though not nausea) in head-to-head comparison 5
• Treatment alteration from metoclopramide to ondansetron (31.8%) was significantly more common than the reverse (4.4%), suggesting some patients require ondansetron for adequate symptom control 6

Important Safety Considerations

• Both metoclopramide and ondansetron can cause extrapyramidal symptoms and oculogyric crises 1
• Metoclopramide should be administered intravenously by slow bolus over at least 3 minutes to minimize extrapyramidal effects 2
• If adverse reactions occur with either medication, prompt cessation is required 2
• Metoclopramide is also safe during breastfeeding 1

Clinical Algorithm

1. Start with metoclopramide for nausea/vomiting in pregnancy 1, 2
2. If metoclopramide is ineffective or not tolerated, consider ondansetron as second-line therapy 2
3. Counsel patients about the small increased risk of orofacial clefts with first-trimester ondansetron use 1, 2
4. Monitor for extrapyramidal symptoms with both medications 1, 2
5. Consider combination therapy if single agents fail 2