Doxylamine is a first-generation antihistamine belonging to the ethanolamine class, primarily used for its sedative and anti-allergic properties. It works by blocking H1 histamine receptors, thereby reducing allergy symptoms such as runny nose, sneezing, and itching. Due to its strong sedative effect, it is commonly employed as an over-the-counter sleep aid for short-term treatment of insomnia. Doxylamine is also included in combination with other medications, such as pyridoxine, for the treatment of nausea and vomiting in pregnancy. Its onset of action is relatively rapid, and it is usually well-absorbed when administered orally. The drug is metabolized in the liver and excreted primarily via the urine. Common side effects include drowsiness, dry mouth, and mild gastrointestinal disturbances. Caution is advised when used in the elderly or in patients with respiratory conditions due to potential sedation and anticholinergic effects. Doxylamine has also been studied for its off-label use in certain sleep disorders and as part of combination therapy for cold and allergy relief. Its widespread availability and effectiveness make it a commonly used and well-recognized antihistamine worldwide.
BRAND NAMES
Doxylamine is marketed under several brand names worldwide. Common ones include Unisom, NyQuil (as part of combination products), and Doxylamine Succinate OTC. It is available in tablets, capsules, and liquid formulations. Brand names may vary by country depending on regulatory approvals. It is often combined with other agents like pyridoxine for anti-nausea therapy in pregnancy.
MECHANISM OF ACTION
Doxylamine is a first-generation H1 histamine receptor antagonist. By blocking H1 receptors, it prevents histamine from causing allergic symptoms like sneezing, itching, and nasal congestion. It also crosses the blood-brain barrier, leading to sedation through central nervous system depression. Its anticholinergic properties contribute to drying secretions in the upper respiratory tract. This combination of antihistamine and sedative effects underlies its dual use in allergies and insomnia.
PHARMACOKINETICS:
Absorption
Doxylamine is rapidly absorbed after oral administration. Peak plasma concentrations are typically reached within 1–2 hours. Food slightly delays absorption but does not significantly affect bioavailability. Its high oral absorption contributes to its prompt onset of action.
Distribution
The drug is widely distributed in body tissues, including the central nervous system, accounting for its sedative effects. It is highly protein-bound, which affects its interaction with other drugs. Volume of distribution allows effective tissue penetration.
Metabolism
Doxylamine is primarily metabolized in the liver via oxidative pathways. Several metabolites are produced, though most pharmacological activity is from the parent compound. Metabolism may vary with age and hepatic function.
Excretion
Excretion occurs mainly via urine as unchanged drug and metabolites. The elimination half-life ranges from 10 to 12 hours, allowing for once-daily dosing at bedtime. Minimal fecal excretion occurs.
PHARMACODYNAMICS
Doxylamine exerts its effect by blocking histamine H1 receptors in peripheral tissues and the CNS. Its sedative effects arise from central H1 receptor blockade in the brain. Anticholinergic activity reduces mucous secretions and may cause dry mouth. The onset of action is fast, typically within 30 minutes to 1 hour. Duration of action is generally 6–8 hours, making it effective for overnight symptom relief.
ADMINISTRATION
Doxylamine is administered orally in the form of tablets, capsules, or liquid. It is usually taken 30 minutes before bedtime for insomnia. For nausea in pregnancy, dosing is adjusted and often combined with pyridoxine. Tablets should be swallowed whole with water. Dosage timing should avoid daytime sedation in sens13itive patients.
DOSAGE AND STRENGTH
Common adult dosage for insomnia is 25 mg at bedtime. Pediatric dosing is lower and adjusted according to age and weight. For nausea in pregnancy, combination therapy with pyridoxine is used at prescribed amounts. Over-the-counter formulations may vary in strength. Dosage should not exceed recommended limits to prevent excessive sedation.
DRUG INTERACTIONS
Doxylamine can interact with other CNS depressants like alcohol, opioids, or benzodiazepines, enhancing sedation. Anticholinergic drugs may increase the risk of side effects like dry mouth or urinary retention. Concurrent use with MAO inhibitors may intensify anticholinergic effects. Interactions with liver-metabolized drugs can alter drug levels. Monitoring is advised in polypharmacy situations.
FOOD INTERACTIONS
Food may slightly delay absorption but does not significantly affect bioavailability. Alcohol should be avoided due to enhanced sedation. High-fat meals may increase CNS effects. Caffeine may reduce sedative effectiveness. No significant interactions with common foods are documented beyond these considerations.
CONTRAINDICATIONS
Doxylamine is contraindicated in patients with hypersensitivity to the drug or other ethanolamine antihistamines. It should be avoided in narrow-angle glaucoma, severe urinary retention, or known hypersensitivity to antihistamines. Caution is required in pregnancy unless prescribed for nausea. Use in breastfeeding women is limited and should be evaluated by a physician.
SIDE EFFECTS
Feeling sleepy or groggy the next day
Experiencing dizziness or a spinning sensation
Dryness in the mouth, nose, or throat
Constipation or difficulty with bowel movements
Blurred or double vision
Headaches or mild head discomfort
Upset stomach, nausea, or diarrhea
Restlessness or heightened activity, especially in children
OVER DOSE
Symptoms of overdose include extreme drowsiness, confusion, hallucinations, dry mouth, dilated pupils, and in severe cases, seizures or coma. Treatment is primarily supportive, including gastric lavage and activated charcoal if ingestion is recent. Monitoring of vital signs and cardiac function is recommended. There is no specific antidote. Patients should be observed until fully recovered.
TOXICITY
Doxylamine has a relatively wide therapeutic index, but high doses can cause severe CNS depression. Chronic misuse or overdose may lead to hepatotoxicity or cardiovascular complications. Anticholinergic toxicity can exacerbate pre-existing conditions like glaucoma or urinary retention. Lethal outcomes are rare but possible in massive ingestion. Safety is optimized by adhering strictly to recommended dosing guidelines.
