DOXYLAMINE SUCCINATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE (DOXYLAMINE SUCCINATE).
Antagonist at histamine H1 receptors, producing sedative and antihistaminic effects; also possesses anticholinergic properties.
| Metabolism | Primarily hepatic via CYP450 enzymes (CYP2D6, CYP1A2, and others); undergoes N-demethylation and other oxidative pathways. |
| Excretion | Renal excretion of metabolites (30-60% as conjugated metabolites, <5% unchanged). Fecal elimination is minor (<10%). |
| Half-life | Terminal elimination half-life ranges from 10 to 12 hours in adults. In elderly patients, half-life may be prolonged (up to 15-18 hours) due to reduced renal clearance. |
| Protein binding | Approximately 80-90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is 2.5-4.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70-80% due to first-pass metabolism. |
| Onset of Action | Oral administration: Onset of sedation occurs within 30 minutes; peak effect at 1-2.5 hours. |
| Duration of Action | Duration of sedative effect is 6-8 hours. Antihistaminic effects may persist longer (up to 12 hours). Clinical note: Tolerance to sedative effects may develop with continued use. |
6.25 to 25 mg orally every 4 to 6 hours as needed, not to exceed 150 mg per day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No specific dose adjustment recommended; use with caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Children 6-11 years: 3.125 to 6.25 mg orally every 4-6 hours, not to exceed 37.5 mg/day. Children 12 years and older: same as adult dosing. |
| Geriatric use | Initiate at the lowest effective dose (e.g., 6.25 mg) due to increased sensitivity and risk of anticholinergic effects, sedation, and falls. Maximum recommended dose: 100 mg per day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE (DOXYLAMINE SUCCINATE).
| Breastfeeding | Doxylamine passes into breast milk in small amounts. The M/P ratio is not established. Single doses are considered compatible with breastfeeding; caution with chronic or high doses due to potential infant sedation or irritability. |
| Teratogenic Risk | First trimester: Doxylamine succinate is a pregnancy category A antihistamine used for nausea and vomiting of pregnancy (NVP). Studies in pregnant women have not shown an increased risk of congenital malformations. Second and third trimesters: No evidence of fetal harm; safety established for use in NVP. No known teratogenic effects. |
■ FDA Black Box Warning
Not applicable; no FDA black box warning.
| Serious Effects |
["Hypersensitivity to doxylamine or any component","Concurrent use with MAO inhibitors (may prolong anticholinergic effects)","Acute asthma attack","Severe liver disease","Narrow-angle glaucoma","Symptomatic prostatic hypertrophy","Breastfeeding (may cause sedation in infant)"]
| Precautions | ["May cause marked drowsiness and impair mental/physical abilities","Avoid alcohol and other CNS depressants","Use with caution in elderly (increased risk of falls, confusion, anticholinergic effects)","May exacerbate urinary retention, glaucoma, or hyperthyroidism","Not recommended for use in children under 6 years for insomnia","May cause paradoxical excitation in children or elderly"] |
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| Fetal Monitoring | No specific maternal or fetal monitoring required for standard use. In overdose or prolonged use, monitor for maternal CNS depression (drowsiness, dizziness) and fetal heart rate if late pregnancy. |
| Fertility Effects | No adverse effects on fertility reported in human studies. Anticholinergic properties do not impair reproductive function. No evidence of reduced conception rates. |