|Trade names Unisom|
ATC code R06AA09 (WHO)
CAS ID 469-21-6
Routes of administration Oral
Molar mass 270.369 g/mol
|Pregnancy category AU: A US: B (No risk in non-human studies) A (Briggs)|
Doxylamine is a first-generation antihistamine. It can be used by itself as a short-term sedative and in combination with other drugs to provide night-time allergy and cold relief. Doxylamine is also used in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women. Its fetal safety is "A" in Briggs’ Reference Guide to Foetal and Neonatal Risk.
It is used in the combination drug Pyridoxine/doxylamine to treat nausea and vomiting of pregnancy.
As of 2004, doxylamine and diphenhydramine were the agents most commonly used to treat short term insomnia. As of 2008, antihistamines were not recommended by the American Academy of Sleep Medicine for treatment of chronic insomnia "due to the relative lack of efficacy and safety data.".
The main metabolites are N-desmethyldoxylamine, N,N-didesmethyldoxylamine, and doxylamine N-oxide.
Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines, such as cetirizine (Zyrtec) or diphenhydramine (Benadryl), as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended. However, the drug is not addictive, and withdrawal effects are unlikely to be experienced with prolonged use.
Doxylamine succinate is generally safe for administration to healthy adults. The median lethal dose (LD50) is estimated to be 50–500 mg/kg in humans. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic (or grand mal) seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3-year old child died 18 hours after ingesting 1,000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis and acute renal failure.
Studies of doxylamine's carcinogenicity in mice and rats have produced positive results for both liver and thyroid cancer, especially in the mouse. The carcinogenicity of the drug in humans is not well studied, and the IARC lists the drug as "not classifiable as to its carcinogenicity to humans".
Doxylamine is a first-generation antihistamine, first reported in 1949.
Doxylamine is primarily used as the succinic acid salt, doxylamine succinate.
It is marketed under the names Restavit and Dozile), Russia (Valocordin-Doxylamine) and India (Vomentin).