Doxylamine

Mechanism of action

◎Histamine H1 receptorDoxylamine

ⓘ The figure shows doxepin, a first-generation H1 blocker, in the human H1 receptor; doxylamine binds the same site (no doxylamine structure is available).

Doxylamine, an ethanolamine antihistamine, crosses into the brain and blocks (as an inverse agonist) H1 receptors of the histamine wake-promoting system, causing drowsiness. It also blocks muscarinic receptors, which explains the dry mouth, blurred vision and urinary retention. H1 and muscarinic block in the vestibular and vomiting pathways reduce nausea; combined with vitamin B6 (pyridoxine) it is used for nausea and vomiting of pregnancy.

1. Enters the brain and blocks H1 receptors
2. Histamine wake signal falls: drowsiness
3. Muscarinic block: dry mouth, urinary retention
4. With pyridoxine: less nausea in pregnancy

Indications

• Short-term relief of occasional insomnia (over the counter) Insomnia disorder →
• Nausea and vomiting of pregnancy, with pyridoxine Hyperemesis gravidarum →
• Ingredient of night-time cold and flu combinations

Adverse effects

Common

• Drowsiness the next day
• Dry mouth, nose and throat
• Headache, dizziness, restlessness
• Constipation or stomach upset

Contraindications

• MAO inhibitors now or within two weeks (pyridoxine combination)
• Caution or avoidance in glaucoma, urinary retention from prostate enlargement, asthma, peptic ulcer or bowel obstruction
• Generally avoided in people aged 65 or older; safer options exist

Key interactions

Alcohol and other CNS depressants

Much more drowsiness.

MAO inhibitors

Listed as a precaution with the pyridoxine combination; the combination is avoided.

Other anticholinergic drugs

Additive dry mouth, constipation, urinary retention and confusion.

What is monitored

• Daytime sleepiness and falls
• Urinary retention and constipation
• Duration of use for insomnia (short-term only)

Administration and safety

• Sleep aid: taken about half an hour before bedtime, with enough time for a full night's sleep; for short-term use only.
• Pregnancy tablet (with pyridoxine): taken at bedtime on an empty stomach, swallowed whole, not crushed or split.
• Not combined with other products that contain an antihistamine.

Pregnancy and breastfeeding

With pyridoxine it is a treatment for nausea and vomiting of pregnancy; the combination is not taken while breastfeeding.

Nursing care

• Before: ask about glaucoma, prostate problems, asthma and age over 65.
• During: warn about next-day drowsiness; no driving until the effect is known.
• Teach to avoid alcohol and to report difficulty urinating or blurred vision.
• Advise a review if sleep problems last more than two weeks.

Pharmacokinetics

Absorption

Oral; the pyridoxine combination is a delayed- or extended-release tablet.

Onset and duration

As a sleep aid it is taken shortly before bedtime.

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Connections

← Back to the class: H1 antihistamines

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Doxylamine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Doxylamine and Pyridoxine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Structure of the human histamine H1 receptor in complex with doxepin (RCSB Protein Data Bank, 2011); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.