Doxylamine Dosing
For adults and adolescents 12 years and older, the FDA-approved dose of doxylamine is 25 mg taken 30 minutes before bedtime, once daily; doxylamine is not approved for use in children under 12 years of age. 1
Adult Dosing
- Standard dose: 25 mg (one tablet) taken 30 minutes before bedtime, once daily 1
- The active ingredient in each tablet is doxylamine succinate 25 mg 1
- Lower doses (12.5 mg) are available in some markets and demonstrate dose-proportional pharmacokinetics, meaning systemic exposure increases predictably and linearly with dose 2
- Doses ranging from 12.5 mg to 25 mg show proportional increases in maximum plasma concentration (Cmax) and area under the curve (AUC), with mean Cmax of 61.94 ng/mL for 12.5 mg and 124.91 ng/mL for 25 mg 2
Pediatric Dosing
- Children under 12 years: Do not use 1
- The FDA label explicitly states that doxylamine should not be administered to children under 12 years of age 1
- This contraindication aligns with broader safety concerns about first-generation antihistamines in young children, as 33 deaths were associated with diphenhydramine (a similar first-generation antihistamine) in children under 6 years between 1969-2006 3
Special Population: Pregnancy (Nausea and Vomiting)
While not the primary indication for doxylamine as a sleep aid, the doxylamine-pyridoxine combination is FDA-approved for nausea and vomiting of pregnancy:
- Standard dose: Up to 4 tablets daily of the delayed-release combination (each containing doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) 4
- Higher doses: When needed for body weight normalization or symptom optimization, doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets) have been studied without increased maternal adverse effects or adverse pregnancy outcomes 5
- The medication is safe and well-tolerated at doses up to 4 tablets daily based on randomized controlled trial data 4
Pharmacokinetic Considerations
- Time to maximum concentration: Oral tablets achieve peak plasma levels without a significantly faster onset compared to intranasal formulations 6
- Duration of action: Doxylamine has a relatively long half-life, making it suitable for once-daily bedtime dosing 7
- Bioavailability: Oral administration provides predictable, dose-proportional systemic exposure 2
Common Adverse Effects
- The most frequently reported adverse effects are somnolence, tiredness, and drowsiness, which are expected given the medication's sedative properties 5, 2
- With intranasal formulations (not FDA-approved), nasal congestion, nasal dryness, and frontal headache were reported 6
- Adverse effects occur in approximately one-third (33.6%) of users and are not dose-dependent within the therapeutic range 5
Critical Safety Warnings
- Not for children under 12 years: This is an absolute contraindication per FDA labeling 1
- Sedation risk: Users should be counseled about significant sedative effects that may impair next-day functioning 5, 2
- Single daily dose only: The medication should be taken once daily at bedtime, not multiple times per day for insomnia 1