Clinical safety rating: safe
Combined with pyridoxine (Vitamin B6) as Diclegis (delayed-release) or Bonjesta — the only FDA-approved medication specifically for nausea and vomiting of pregnancy (NVP). Extensive post-marketing surveillance from its earlier formulation (Bendectin) across millions of exposures showed no teratogenicity. Withdrawn from the US market in 1983 due to litigation despite no scientific evidence of harm; re-approved in 2013 after full FDA review.
Doxylamine is a first-generation antihistamine with sedative properties. It acts as a competitive antagonist at histamine H1 receptors, thereby blocking the effects of histamine. It also possesses anticholinergic activity.
| Metabolism | Metabolized primarily by the liver, likely via hydroxylation and conjugation; specific cytochrome P450 enzymes not well characterized. |
| Excretion | Renal (approximately 60% as unchanged drug and metabolites, primarily as N-desmethyldoxylamine and other metabolites); biliary/fecal (minor). |
| Half-life | 10-12 hours; prolonged in elderly and hepatic impairment. |
| Protein binding | Approximately 60-70%, primarily to albumin. |
| Volume of Distribution | 2.5-3.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: ~70-80% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes for sedative effect. |
| Duration of Action | Sedation lasts 4-6 hours, but antihistaminic effects may persist up to 8 hours. |
| Molecular Weight | 270.37 |
| Action Class | First-generation antihistamine (ethanolamine class); sedating antihistamine. |
12.5–25 mg orally at bedtime for insomnia; 25 mg orally every 4–6 hours as needed for allergies (max 150 mg/day).
| Renal impairment | No specific dosage adjustment guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to increased risk of accumulation and anticholinergic effects. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C); for Child-Pugh A or B, use lowest effective dose and monitor closely for sedation and confusion. |
| Pediatric use | For children ≥12 years: 25 mg orally every 4–6 hours as needed (max 150 mg/day). For children 6–11 years: 6.25 mg (half of a 12.5 mg tablet) every 4–6 hours (max 37.5 mg/day). Not recommended for children <6 years. |
| Geriatric use | Initiate with 6.25 mg (half of a 12.5 mg tablet) at bedtime; avoid chronic use due to increased risk of sedation, dizziness, and anticholinergic effects (e.g., confusion, urinary retention). |
| 1st trimester | Limited human data; animal studies not suggestive of risk. Avoid in first trimester due to potential anticholinergic effects. |
| 2nd trimester | Use with caution; no known teratogenicity but limited data. |
| 3rd trimester | Avoid near term due to anticholinergic effects in neonate (e.g., irritability, abnormal feeding). |
Clinical note
Combined with pyridoxine (Vitamin B6) as Diclegis (delayed-release) or Bonjesta — the only FDA-approved medication specifically for nausea and vomiting of pregnancy (NVP). Extensive post-marketing surveillance from its earlier formulation (Bendectin) across millions of exposures showed no teratogenicity. Withdrawn from the US market in 1983 due to litigation despite no scientific evidence of harm; re-approved in 2013 after full FDA review.
| Placental transfer | Crosses placenta; extent not well quantified. |
| Breastfeeding | Small amounts excreted in breast milk; may cause sedation in infant. Use with caution, especially in premature neonates or those with apnea risk. |
■ FDA Black Box Warning
None.
| Common Effects | Drowsiness, Dizziness, Dry mouth, nose, and throat, Blurred vision, Constipation, Urinary retention, Thickened bronchial secretions, Nausea |
| Serious Effects | Respiratory depression (especially in children or with overdose), Seizures, Cardiac arrhythmias (e.g., QT prolongation, torsades de pointes), Severe anticholinergic effects (e.g., delirium, hyperthermia, urinary retention), Rhabdomyolysis (with overdose), Anaphylaxis |
Hypersensitivity to doxylamine or other ethanolamine derivativesAcute asthma attackAngle-closure glaucomaProstatic hypertrophyUrinary retentionPyloroduodenal obstruction
| Precautions | Use with caution in patients with asthma, chronic obstructive pulmonary disease (COPD), glaucoma, urinary retention, prostate hypertrophy, and pyloric obstruction., May cause central nervous system depression; avoid concurrent use with alcohol or other sedatives., May impair mental and physical abilities; caution when driving or operating machinery., Use with caution in patients with cardiovascular disease or hypertension., Anticholinergic effects may exacerbate glaucoma, urinary retention, and constipation. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category A. No evidence of increased risk of fetal abnormalities in first trimester. In second and third trimesters, no known risks. However, use in late pregnancy may be associated with neonatal withdrawal symptoms or respiratory depression if used near term. |
| Fetal Monitoring | Routine monitoring for sedation and anticholinergic effects. No specific fetal monitoring required unless used near term or in high doses. |
| Fertility Effects | No documented adverse effects on fertility or reproductive function in human studies. At high doses, animal studies have shown minimal effects, but clinical relevance is unknown. |
| Food/Dietary | Avoid alcohol and grapefruit juice; grapefruit may increase sedative effects. No significant food restrictions, but taking with a small snack may reduce GI upset. Caffeinated beverages should be limited during the day to minimize insomnia. |
| Clinical Pearls | Doxylamine is a first-generation antihistamine with strong sedative properties, often used as a short-term sleep aid. Its anticholinergic effects can exacerbate conditions like urinary retention, glaucoma, and dementia. Avoid in elderly due to increased fall risk and confusion. Onset of sedation: 30-60 min; duration: 6-8 hours. |
| Patient Advice | Take doxylamine only when you have at least 7-8 hours to sleep to avoid next-day drowsiness. · Do not combine with alcohol or other sedatives (e.g., benzodiazepines, opioids). · Avoid driving or operating heavy machinery until you know how this drug affects you. · Do not use for more than 7-10 consecutive days for insomnia; see a doctor if symptoms persist. · Report difficulty urinating, blurred vision, or rapid heartbeat immediately. |