What are the recommended medications for a pregnant female in her first trimester experiencing nausea?

First-Line Treatment: Doxylamine-Pyridoxine Combination

For first trimester nausea, start with the FDA-approved combination of doxylamine succinate 10 mg and pyridoxine (vitamin B6) 10 mg as delayed-release tablets (Diclegis), which is the only medication specifically approved for nausea and vomiting in pregnancy and carries FDA Pregnancy Category A status. 1, 2

Treatment Algorithm by Severity

Mild Nausea (PUQE Score ≤6)

• Begin with pyridoxine (vitamin B6) alone at 10-25 mg every 8 hours 1, 3
• If insufficient after 2-3 days, escalate to the doxylamine-pyridoxine combination 1
• Dietary modifications: small, frequent, bland meals and avoidance of triggers 4

Moderate Nausea (PUQE Score 7-12)

• Start directly with doxylamine-pyridoxine combination (Diclegis) 1, 4
• Dosing can be optimized up to 4 tablets daily (taken at bedtime and throughout the day) 1
• If inadequate response after 3-5 days, add second-line agents 1

Severe Nausea or Hyperemesis Gravidarum (PUQE Score ≥13)

• Optimize doxylamine-pyridoxine dosing first 1
• Add metoclopramide 5-10 mg orally every 6-8 hours as the preferred second-line agent 1, 4
• Metoclopramide has comparable efficacy to other antiemetics but with fewer side effects including less drowsiness, dizziness, and dystonia 1, 4

Second-Line Options

Antihistamines (H1-Receptor Antagonists)

• Promethazine is safe throughout pregnancy and can be used when first-line therapy fails 1, 5
• Other antihistamines (dimenhydrinate, meclizine) are also safe alternatives 6, 5

Ondansetron: Use With Caution

• Reserve ondansetron as second-line therapy and use cautiously before 10 weeks gestation 1, 4
• There is a small absolute risk increase of cleft palate (0.03%) and ventricular septal defects (0.3%) with first-trimester use 1
• ACOG recommends case-by-case decision-making for ondansetron use before 10 weeks 1, 4
• Despite safety concerns, ondansetron prescriptions have increased dramatically in the U.S., with 110,000 monthly prescriptions by 2013 7

Critical Safety Measures

Thiamine Supplementation

Always provide thiamine supplementation in cases of prolonged vomiting to prevent Wernicke encephalopathy 1, 4

• Oral: 100 mg daily for minimum 7 days, then 50 mg daily maintenance 4
• IV (if unable to tolerate oral): 200-300 mg daily 4

Last-Resort Therapy

Methylprednisolone should only be used for severe, refractory hyperemesis gravidarum after other therapies have failed 1, 4

• Dosing: 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks 1, 4
• Avoid before 10 weeks gestation due to small risk of cleft palate 1, 4

Common Pitfalls to Avoid

• Don't prescribe ondansetron as first-line therapy: Despite its widespread use (97.7% of NVP prescriptions in the U.S. are off-label medications), doxylamine-pyridoxine is safer and FDA-approved specifically for this indication 7, 2
• Don't delay pharmacologic treatment: Early intervention prevents progression to hyperemesis gravidarum 1, 4
• Don't forget thiamine: Pregnancy increases thiamine requirements, and hyperemesis can deplete stores within 7-8 weeks 4
• Don't use glyburide or metformin for nausea: These are diabetes medications that cross the placenta and are not indicated for nausea 6

When to Hospitalize

Consider hospitalization for IV therapy if: 1, 4

• Persistent vomiting despite oral antiemetics
• Signs of dehydration or electrolyte abnormalities
• Weight loss >5% of pre-pregnancy weight
• Inability to tolerate oral intake
• Ketonuria present