What are the recommended medications for treating nausea in pregnant individuals?

Nausea Medications in Pregnancy

Start with vitamin B6 (pyridoxine) 10-25 mg every 8 hours as first-line treatment, escalate to doxylamine-pyridoxine combination if insufficient, then metoclopramide 5-10 mg every 6-8 hours for refractory cases, reserving ondansetron only after 10 weeks gestation when other options fail. 1

First-Line Treatment: Vitamin B6 (Pyridoxine)

• Begin with pyridoxine 10-25 mg orally every 8 hours for mild nausea, which has established safety at doses up to 40-60 mg/day throughout pregnancy 1, 2
• Pyridoxine alone demonstrates significant improvement in nausea symptoms with a Rhode's score reduction of 0.78 (95% CI: 0.26,1.31) 3
• If symptoms persist after 2-3 days of pyridoxine monotherapy, escalate to combination therapy rather than continuing ineffective monotherapy 1

Second-Line: Doxylamine-Pyridoxine Combination

• Escalate to doxylamine-pyridoxine 10 mg/10 mg delayed-release formulation when pyridoxine alone is insufficient, which is the only FDA-approved medication specifically for nausea and vomiting in pregnancy 1, 4
• This combination qualifies for FDA Pregnancy Category A status based on safety data from over 200,000 first-trimester exposures showing no increased risk of congenital malformations 4, 5
• Dosing can be titrated from 2 to 4 tablets daily depending on symptom severity, taken at bedtime and upon awakening 1

Third-Line: Metoclopramide

• Use metoclopramide 5-10 mg orally every 6-8 hours when first-line therapy fails, as it has an excellent safety profile throughout all trimesters with no significant increase in major congenital defects (OR 1.14,99% CI 0.93-1.38) 1, 6
• Metoclopramide has fewer side effects than promethazine, including less drowsiness, dizziness, and dystonia 1
• Withdraw immediately if extrapyramidal symptoms develop 6

Fourth-Line: Ondansetron (Use with Caution)

• Reserve ondansetron for refractory cases only, particularly after 10 weeks gestation, due to small but measurable teratogenic risks including marginal increases in cleft palate (0.03% absolute increase) and ventricular septal defects (0.3% absolute increase) 1, 6
• Before 10 weeks gestation, use ondansetron only on a case-by-case basis when benefits clearly outweigh risks 1, 6
• Typical dosing is 4-8 mg orally every 8 hours as needed 6

Alternative Antihistamines

• Promethazine, dimenhydrinate, and meclizine are safe alternatives throughout pregnancy with extensive clinical experience, though they cause more sedation than metoclopramide 6
• These can be used interchangeably with doxylamine if the combination product is unavailable 6

Migraine-Associated Nausea in Pregnancy

• Use paracetamol as first-line for migraine pain itself, while NSAIDs are only recommended during the second trimester 7, 1
• Metoclopramide is specifically recommended for migraine-associated nausea in pregnancy 7, 1

Severe Hyperemesis Gravidarum (Last Resort)

• Methylprednisolone 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks, should be reserved for severe, refractory hyperemesis gravidarum unresponsive to all other therapies 1, 6
• Avoid corticosteroids before 10 weeks gestation due to small risk of cleft palate 1
• Always provide thiamine supplementation 100 mg daily for minimum 7 days, then 50 mg daily maintenance in prolonged vomiting to prevent Wernicke encephalopathy 1, 6

Severity Assessment Tool

• Use the PUQE (Pregnancy-Unique Quantification of Emesis) score to quantify severity: mild (≤6), moderate (7-12), severe (≥13) 1, 6
• This score guides treatment intensity and helps track response to therapy 6

Critical Clinical Pearls

• Early pharmacologic intervention is crucial to prevent progression to hyperemesis gravidarum, which affects 0.3-2% of pregnancies 1, 6
• Most nausea and vomiting resolves by week 16-20 in 80% of cases, though 10% experience symptoms throughout pregnancy 6
• Never use sodium valproate, topiramate, or candesartan in pregnancy due to established teratogenic effects 1
• The high placebo response rate in pregnancy nausea trials (often >50%) means that clinical judgment and symptom severity should guide escalation decisions 8