What is the dose and frequency of doxylamine (antihistamine)/pyridoxine (Vitamin B6)?

Doxylamine/Pyridoxine Dosing for Nausea and Vomiting of Pregnancy

The recommended dose is doxylamine 10 mg/pyridoxine 10 mg (Diclegis/Diclectin) starting with 2 tablets at bedtime on Day 1, then titrating up to a maximum of 4 tablets daily based on symptom response using a specific escalation protocol. 1, 2

Standard Dosing Protocol

Initial dosing:

• Day 1: Take 2 tablets (doxylamine 10 mg/pyridoxine 10 mg each) at bedtime 1, 3
• If symptoms are controlled the next day, continue this dose 3

Titration schedule if symptoms persist:

• Day 2: If symptoms persist, take 2 tablets at bedtime PLUS 1 tablet in the morning 3, 4
• Day 3: If symptoms still persist, take 1 tablet in the morning, 1 tablet mid-afternoon, and 2 tablets at bedtime (total of 4 tablets daily) 3, 4
• Maximum dose: 4 tablets per day (doxylamine 40 mg/pyridoxine 40 mg total) 1, 3, 4

Clinical Context

This combination is FDA-approved and recommended as first-line pharmacologic therapy for nausea and vomiting of pregnancy (NVP) by ACOG and the American Gastroenterological Association. 1, 2, 5 The delayed-release formulation allows for once-daily or divided dosing depending on symptom severity and timing 4.

Key advantages:

• Only FDA Pregnancy Category A medication for NVP 4
• Safety data from over 200,000 first-trimester exposures showing no increased risk of congenital malformations 5, 4
• Well-tolerated with no increased adverse events compared to placebo 3

Important Caveats

Efficacy considerations:

• The clinical benefit is modest, with improvement of approximately 0.7-1.25 points on the 13-point PUQE scale, which may not reach the minimal clinically important difference of 3 points 6
• Despite limited magnitude of benefit, it remains first-line therapy due to proven safety profile and FDA approval 1, 2, 5

When this regimen fails:

• For moderate-severe NVP not responding to maximum dose (4 tablets daily), escalate to metoclopramide or ondansetron (with caution before 10 weeks gestation) 1, 2
• Consider hospitalization for IV hydration if severe symptoms persist 1, 2

Distinction from Pyridoxine Supplementation

This dosing is distinct from pyridoxine supplementation for other indications:

• For prevention of isoniazid-induced peripheral neuropathy: pyridoxine 25 mg daily 7
• For pregnant women on isoniazid: pyridoxine 25 mg daily (note: standard multivitamins contain insufficient amounts) 7
• For patients with established peripheral neuropathy: pyridoxine 100 mg daily 7