What medications are safe for treating nausea in a pregnant woman in her 2nd trimester?

Safe Medications for Nausea During Second Trimester Pregnancy

The combination of doxylamine succinate and pyridoxine hydrochloride is the first-line pharmacological treatment for nausea and vomiting during pregnancy, including the second trimester, with a pregnancy safety rating of A. 1

First-Line Treatments

• Pyridoxine (Vitamin B6): 10-25 mg orally every 8 hours is recommended as initial therapy for mild nausea and vomiting during pregnancy 1
• Doxylamine-pyridoxine combination: Delayed-release combination of doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg is the preferred first-line pharmacological treatment 1, 2
• Early treatment is crucial as it may prevent progression to hyperemesis gravidarum, which affects 0.3-2% of pregnancies 1

Second-Line Treatments

If symptoms persist despite first-line therapy, consider adding:

• Metoclopramide: 5-10 mg orally every 6-8 hours is safe during pregnancy with no significant increase in risk of major congenital defects (odds ratio 1.14,99% CI 0.93-1.38) 1
• Antihistamines: Such as dimenhydrinate can be added to first-line treatment 3
• Promethazine: Can be used as a second-line agent, particularly when other treatments have failed 3

Third-Line Treatments

• Ondansetron: Can be used as a third-line agent, but with caution before 10 weeks of pregnancy due to a marginal relative increase in risk of cleft palate (0.03% absolute increase) and cardiovascular malformations, particularly ventricular septal defects (0.3% absolute increase) 1
• The American College of Obstetricians and Gynecologists recommends using ondansetron on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 1

Severe Cases (Hyperemesis Gravidarum)

• Methylprednisolone: Can be considered as a last resort for severe nausea and vomiting, but should be avoided before 10 weeks gestation due to a small risk of cleft palate 1
• Thiamine supplementation: Should be considered in cases of prolonged vomiting to prevent Wernicke encephalopathy 1
• IV hydration: May be necessary with replacement of electrolytes, vitamins, and nutrients for severe cases requiring hospitalization 1

Treatment Algorithm

1. Start with dietary and lifestyle modifications

   • Small, frequent meals
   • Avoiding triggers
   • Separating solids and liquids 1

2. For mild symptoms (PUQE score ≤6):

   • Add pyridoxine (vitamin B6) 10-25 mg every 8 hours 1
   • If insufficient, add doxylamine 1, 4

3. For moderate symptoms (PUQE score 7-12):

   • Optimize doxylamine-pyridoxine dosing 1
   • If inadequate response, add metoclopramide 1

4. For severe symptoms (PUQE score ≥13):

   • Consider adding promethazine or ondansetron 1, 3
   • For refractory cases, consider methylprednisolone after the first trimester 1

Important Considerations

• Efficacy of pyridoxine alone or in combination with doxylamine has been demonstrated in multiple studies 5, 6
• Avoid neurokinin-1 antagonists like aprepitant and second-generation antipsychotics like olanzapine unless absolutely necessary, as safety data during pregnancy are limited 1
• The magnitude of benefit with doxylamine-pyridoxine may be modest (0.73 points improvement on the PUQE scale with last observation carried forward), but the safety profile makes it appropriate as first-line therapy 6