Products
Doxylamine is commercially available in many countries as a solution (Sanalepsi N). It is also contained in Vicks MediNait juice in combination with dextromethorphan, ephedrine, and acetaminophen. In 2020, hard capsules containing doxylamine and pyridoxine were approved in many countries for the treatment of nausea and vomiting in pregnancy (Cariban). Pharmacies also make a mixture with valerian tincture; see Sanalepsi with Valerian.
Structure and properties
Doxylamine (C17H22N2O, Mr = 270.4 g/mol) is a racemate and is present in drugs as doxylamine hydrogen succinate, a white powder that is readily soluble in water. It belongs to the ethanolamine and pyridine derivatives.
Effects
Doxylamine (ATC R06AA09) has antihistamine, antiallergic, sedative, depressant, sleep-inducing, and antiemetic properties. The effects are due to antagonism at histamine and muscarinic receptors. Doxylamine has a half-life of approximately 10 hours. Unlike modern 2nd-generation antihistamines, doxylamine is not selective for the H1 receptor and is centrally active.
Indications
Doxylamine is approved in many countries for the short-term treatment of nervousness associated with difficulty falling asleep, for the treatment of allergic rhinitis (eg, hay fever), and for the treatment of flu and cold symptoms (combination preparations). Cariban: Since 2020, doxylamine (in combination with pyridoxine) has also been approved in many countries for the treatment of nausea and vomiting in pregnancy.
Dosage
According to the prescribing information. The drops are taken up to three times daily with meals or half an hour before bedtime for sleep disturbances.
Abuse
Doxylamine can be abused due to its depressant and anticholinergic properties. In practice, it is also observed to be used for long-term therapy of sleep disorders for which it is not intended. Suicide attempts with a toxic overdose have been described in the literature. Actor Heath Ledger (, ) died from a drug cocktail that included doxylamine.
Contraindications
- Hypersensitivity
- Acute asthma attack
- Narrow-angle glaucoma
- Pheochromocytoma
- Bladder emptying disorder with residual urine formation
- Epilepsy
- Concurrent treatment with MAO inhibitors.
- Acute alcohol or drug intoxication
- Children under 12 years
Full precautions can be found in the drug label.
Interactions
Concomitant administration of centrally depressant drugs, alcohol, and anticholinergics may result in an increase in effect and is not recommended. Other interactions have been described with phenytoin, neuroleptics, ototoxic agents, and epinephrine.
Adverse effects
The most common potential adverse effects include fatigue, reduction in responsiveness, paradoxical reactions such as agitation and hallucinations in children and the elderly, headache, and anticholinergic side effects such as dry mouth, impaired accommodation, constipation, and urinary retention. Rarely, cardiovascular reactions such as low or high blood pressure or cardiac arrhythmias may occur.
