Doxylamine, sold under brand names such as Unisom, is an antihistamine used to treat insomnia and allergies. It is also used to treat morning sickness in pregnant women. It belongs to the first-generation class of histamine receptor H1 antagonist drugs. Doxylamine is an over-the-counter medicine taken in nighttime cold remedies, such as NyQuil, as well as pain relievers acetaminophen and codeine to help with sleep relief. The drug is taken by mouth.
Side effects of doxylamine include dizziness, drowsiness, grogginess, and dry mouth. Doxylamine is an antihistamine, specifically an inverse agonist of the histamine H1 receptor, and to a lesser extent an anticholinergic, specifically the muscarinic acetylcholine receptor M1 Antagonist to M5. It is a first-generation antihistamine that crosses the blood-brain barrier and enters the brain, producing centrally mediated sedative and hypnotic effects.
medical use
Doxylamine is an antihistamine used to treat sneezing, runny nose, watery eyes, hives, rashes, itching, and other cold or allergy symptoms. It is also used as a short-term treatment for insomnia.
Insomnia
The first-generation sedating antihistamines diphenhydramine, doxepin, doxylamine, and pyrilamine are the most widely used drugs in the world for the prevention and treatment of insomnia. As of 2004, doxylamine and diphenhydramine, both over-the-counter medications, were the most commonly used drugs to treat short-term insomnia. As of 2008 and 2017, the American Academy of Sleep Medicine did not recommend the use of over-the-counter antihistamines for the treatment of chronic insomnia "due to the relative lack of efficacy and safety data." Although diphenhydramine was discussed, none of their guideline versions explicitly included or mentioned doxylamine. A 2015 systematic review of over-the-counter sleep aids, including doxylamine, found little evidence for using doxylamine to treat insomnia.
Doxylamine doses for sleep range from 5 to 50 mg, with 25 mg being a typical dose.
morning sickness
Doxylamine is used in the combination drug pyridoxine/doxylamine to treat morning sickness (nausea and vomiting of pregnancy). It is the only drug approved by the U.S. Food and Drug Administration to treat morning sickness.
Doxylamine availability status
Doxylamine is used medically as doxylamine succinate (the succinate salt of doxylamine), either alone (trade names Decapryn, Doxy-Sleep-Aid, Unisom) or with pyridoxine (a form of vitamin B6) used in combination with (trade names: Bendectin, Bonjesta, Dickis). Doxylamine is available alone as an immediate-release oral tablet containing 25 mg of doxylamine succinate. Oral tablets containing 12.5 mg of doxylamine succinate and oral capsules containing 25 mg of doxylamine succinate were previously available, but these have been discontinued. The combination of doxylamine and pyridoxine is available as extended-release and delayed-release oral tablets containing 10 to 20 mg of doxylamine succinate and 10 to 20 mg of pyridoxine hydrochloride. Doxylamine is available over-the-counter alone, while doxylamine and pyridoxine are available by prescription. Doxylamine is also found in over-the-counter nighttime cold products, such as NyQuil Cold & Flu (containing acetaminophen, doxylamine succinate 6.25 to 12.5 mg, and dextromethorphan hydrobromide), where it is used as a sedative ingredient .
To treat nausea and vomiting during pregnancy, doxylamine is usually given as an extended-release oral tablet (doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg) with pyridoxine (vitamin B6). Do not crush, chew, or split tablets to maintain extended release. For NVP, the recommended dose is the first two tablets taken. Drink water on an empty stomach and stay in bed. If symptoms persist the next day, patients can take one pill upon waking in the morning and two pills at night. If symptoms are not adequately controlled after taking three tablets on the third day, the dose can be increased to four tablets per day: one in the morning, one in the afternoon and two at bedtime. The maximum daily limit is four tablets.
Patients should not take doxylamine/pyridoxine as needed for treatment of NVP. The need for continued treatment needs to be reassessed throughout pregnancy.
Doxylamine is also available as a stand-alone drug in 25 mg doxylamine succinate oral tablets, available in both brand-name and generic forms. Adult doses of doxylamine are as follows:
- For insomnia (adults and children 12 years and older): Take 25 to 50 mg orally 30 minutes before bed as needed.
- For allergy symptoms (adults and children 12 years and older): 12.5 mg orally every 4 to 6 hours as needed, maximum daily dose is 75 mg.
Hepatic and renal dose adjustments have not been determined.
Contraindications
A contraindication to doxylamine treatment includes concurrent use of monoamine oxidase inhibitors (MAOIs). Allergy to doxylamine is also a risk factor and its use is contraindicated. Concomitant use of alcohol is contraindicated as it can cause significant drowsiness when combined with doxylamine. Caution should be used when coadministering CNS depressant drugs. Contraindications to doxylamine also include patients with elevated intraocular pressure, narrow-angle glaucoma, asthma, stenotic peptic ulcers, bladder neck obstruction, and gastric outlet obstruction.
Doxylamine should not be used in children under two years of age.
Doxylamine has a fetal safety rating of "A" (no evidence of risk)
side effect
Side effects of doxylamine include dizziness, drowsiness, and dry mouth. Doxylamine is a potent anticholinergic drug with side effects common to this class of drugs, including blurred vision, dry mouth, constipation, muscle incoordination, urinary retention, confusion, and delirium.
Due to its relatively long elimination half-life (10-12 hours), doxylamine is associated with next-day side effects when used as a hypnotic, including sedation, drowsiness, groggy, dry mouth, and fatigue. This can be described as the "hangover effect." Diphenhydramine has a shorter elimination half-life (4-8 hours) than doxylamine, which may give it an advantage over doxylamine as a sleep aid in this regard.
Antihistamines such as doxylamine have an initial sedative effect, but repeated use can develop tolerance and may lead to rebound insomnia after discontinuation.
Coma and rhabdomyolysis have been reported occasionally with the use of doxylamine. This is the opposite of diphenhydramine.
Carcinogenicity studies of doxylamine in mice and rats produced positive results for liver and thyroid cancer, particularly in mice. The drug's carcinogenicity in humans has not been fully studied, and the International Agency for Research on Cancer classifies the drug as "not classifiable based on its carcinogenicity in humans."
Continuous and/or cumulative use of anticholinergic drugs, including first-generation antihistamines, is associated with a higher risk of cognitive decline and dementia in older adults.
overdose
Doxylamine is generally safe when taken by healthy adults. Doxylamine has been administered to adults with schizophrenia at doses up to 1,600 mg/day for 6 months with little or no toxicity. The LD50 in humans is estimated to be 50–500 mg/kg. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Deaths have been reported from doxylamine overdose. These symptoms are characterized by coma, tonic-clonic (or grand mal) seizures, and cardiorespiratory arrest. Children appear to be at high risk for cardiorespiratory arrest. Toxic doses in children have been reported to exceed 1.8 mg/kg. A 3-year-old child died 18 hours after ingesting 1,000 mg of doxylamine succinate. In rare cases, overdose can cause rhabdomyolysis and acute kidney injury.
