Doxylamine

Doxylamine is a Histamine H₁ Antagonist belonging to Antiemetic agent.

Doxylamine is an antihistamine used to treat insomnia and allergy symptoms and is used with pyridoxine in the treatment of nausea and vomiting in pregnancy.

Doxylamine is Absorbed easily from the GI tract. The time taken to reach peak plasma concentration is about 2-4 hours. The Volume of distribution is approximately 2.5 L/kg. Doxylamine is metabolized hepatically via N-dealkylation to form metabolites Doxylamine excreted mainly via urine, 60% as unchanged drug.

Doxylamine shows side effects like Dry mouth, nose, and throat, drowsiness, nausea, increased chest congestion, headache, excitement, and nervousness.

Doxylamine is available in the form of Oral Tablet.

Doxylamine is available in India, US, Canada, Japan, China, UK, France, Russia, Malaysia, and Australia.

Doxylamine belongs to the Antiemetic agent acts as a Histamine H₁ Antagonist.

Doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.

The Data of Onset and Duration of action of Doxylamine is not clinically established.

The Tmax of Doxylamine is approximately 2-4 hour.

Doxylamine is available in the form of Oral tablet.

Doxylamine tablet is taken orally, usually once daily.

Doxylamine is used to relieve allergic symptoms and nausea and vomiting (morning sickness) in pregnant women. This medicine is not recommended for use in patients less than 12 years of age.

Doxylamine is a Histamine H₁ Antagonist belonging to Antiemetic agent.

Doxylamine competes with histamine for H₁-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.

Doxylamine is approved for use in the following clinical indications

• Insomnia, sleep onset or sleep maintenance
• Nausea and vomiting, pregnancy associated

• Insomnia, sleep onset or sleep maintenance

Adult Dose:

Oral: 25 mg once daily 30 minutes before bedtime, as needed.

Pediatric Dose

Children ≥12 years and Adolescents: Tablets: Oral: 25 mg once daily before bedtime.

• Nausea and vomiting, pregnancy associated

Oral: Initial: 12.5 to 25 mg once daily at bedtime; if symptoms persist, increase to 12.5 mg in morning or 12.5 mg in morning and mid-afternoon depending on symptom severity, while continuing 12.5 to 25 mg at bedtime.

Doxylamine is available in various strengths as 5mg and 25mg.

Doxylamine is contraindicated in patients with Hypersensitivity.

• CNS depression: May cause CNS depression, that may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery, driving).

Consumption of alcohol is not recommended during treatment with Doxylamine since it may increase the risk of adverse effects such as dizziness, difficulty in concentrating, impaired thinking, etc.

Doxylamine is not recommended for use in breastfeeding women unless necessary. All the risks and benefits should be considered while taking this medicine. If the Doxylamine is used, the patient should be monitored closely for any undesirable side effects.

Doxylamine is not recommended for use in pregnant women unless necessary. All the risks and benefits should be considered while taking Doxylamine.

• Common

CNS depression, stimulation (e.g. insomnia, nervousness, euphoria, irritability, tremors, nightmares, hallucinations, convulsions); headache, lack of coordination, dizziness, psychomotor impairment, constipation, nausea, vomiting, diarrhoea, increased gastric reflux, epigastric pain, thickened resp tract secretions, dry mouth, palpitations, arrhythmias, blurred vision, urinary retention, blood disorders, hypotension, tinnitus, paraesthesia, hypersensitivity reactions.

• Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects.
• Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.
• Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
• Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
• Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.
• Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available.
• Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.
• Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
• Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression.
• Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use.
• Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
• Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

The common side effects of Doxylamine include the following

• Common side effects

Dry mouth, nose, and throat, drowsiness, nausea, increased chest congestion, headache, excitement, and nervousness.

• Rare side effects

Vision problems, difficulty urinating.

Symptoms: Dry mouth, fixed and dilated pupils, flushing, GI symptoms, insomnia, nervousness, euphoria, irritability, tremors, nightmares, hallucinations, CNS depression or stimulation (especially in child), impaired consciousness, seizures, tachycardia, mydriasis, psychosis, rhabdomyolysis, coma, and cardiorespiratory arrest.

Management: Supportive and symptomatic treatment. Ensure adequate ventilation and hydration. Perform gastric lavage or administer activated charcoal w/in 60 min of ingestion. Whole bowel irrigation w/ polyethylene glycol electrolyte may be given to patients w/ extremely large ingestions.

Pharmacodynamic

Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, except for diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.

Pharmacokinetics

• Absorption

Doxylamine is Absorbed easily from the GI tract. Time takes to reach peak plasma concentration is 2-4 hr.

• Distribution

The Volume of distribution is 2.5 L/kg.

• Metabolism and Excretion

Doxylamine is metabolized hepatically via N-dealkylation to form metabolites. Excreted mainly Via urine, 60% as unchanged drug.

• https://www.uptodate.com/contents/doxylamine-drug-information?search=doxylamine&source=panel_search_result&selectedTitle=1~38&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://www.drugs.com/pregnancy/doxylamine.html
• https://go.drugbank.com/drugs/DB00366
• https://medlineplus.gov/druginfo/meds/a682537.html
• https://reference.medscape.com/drug/doxylamine-342933#6
• https://www.mims.com/india/drug/info/doxylamine?type=full&mtype=generic
• https://www.practo.com/medicine-info/doxylamine-1338-api