Doxylamine/pyridoxine

Combination of H1-antihistamine and vitamin B6

ATC code: R06AA09

Updated 1 Jun 2026 · Methodology

Indications

Nausea and vomiting of pregnancy

First line

First-line for mild-to-moderate nausea and vomiting of pregnancy per 2018 and the Spanish SEGO 2022. Starting dose 1 capsule at bedtime; with persistent symptoms, increase to 1 capsule in the morning and 2 at bedtime (up to 40 mg doxylamine and 40 mg pyridoxine daily). Non-pharmacological measures are recommended before drug therapy: small frequent meals, ginger, P6 acupressure. Safety confirmed in a 200,000-pregnancy cohort without described teratogenicity.

Sources

ICD-10: O21 · ICD-11: JA60

Hyperemesis gravidarum

First line

Used in hyperemesis gravidarum within stepwise therapy. 2018 and SEGO 2022 set doxylamine + pyridoxine at maximum dose as first-line. With inadequate effect, add metoclopramide or ondansetron (cautiously in T1); severe cases with dehydration need admission for rehydration and systemic steroids (methylprednisolone).

Sources

ICD-10: O21 · ICD-11: JA60

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Insomnia and sleep disorders

Not recommended

Doxylamine with pyridoxine (Diclectin, Cariban) is a combination drug developed for nausea and vomiting in pregnancy ( 2018 guidelines). In non-pregnant adults it is sometimes used as a mild sleep aid and anxiolytic, purely because of doxylamine's antihistamine effect. There are no clinical trials of this combination in non-pregnant adults for insomnia or anxiety. Doxylamine is a first-generation antihistamine included in the AGS Beers Criteria 2023 as potentially inappropriate for older adults because of anticholinergic effects (confusion, urinary retention, constipation), sedation, orthostatic hypotension, and fall risk. The foundation of insomnia treatment is cognitive-behavioral therapy for insomnia (CBT-I), short-course melatonin, and, when indicated, benzodiazepine receptor agonists or orexin antagonists. If doxylamine was prescribed for sleep in a non-pregnant adult, consider seeking a second opinion.

Sources

ICD-10: G47.0 · ICD-11: 7A00

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Doxylamine is a first-generation H1-antihistamine with antimuscarinic action; blocks the medullary vomiting center. Pyridoxine (vitamin B6) is a cofactor in serotonin, GABA, and dopamine synthesis; exact antiemetic mechanism is unclear, but efficacy is supported by clinical trials. The doxylamine 10 mg + pyridoxine 10 mg combination is first-line for nausea and vomiting of pregnancy per 2018. In Spain sold under the Cariban brand since the 1960s.

Safety

Contraindications

Hypersensitivity to doxylamine, pyridoxine, or other alkylamines
Angle-closure glaucoma
Urinary retention with BPH
Epilepsy with active seizures
Concurrent MAO inhibitors
Age under 18 (use restricted to pregnancy)

Serious adverse effects

Anticholinergic syndrome in overdose
Acute urinary retention
Paradoxical reactions (agitation, insomnia) – rare
Neuropathy with long-term high-dose pyridoxine (over 200 mg/day)

Common adverse effects

Drowsiness (most common)
Dry mouth
Constipation
Dizziness
Fatigue

Pregnancy: can you take Doxylamine/pyridoxine?

AEMPS summary of product characteristics (section 4.6): Cariban (doxylamine and pyridoxine) is indicated in pregnant women. Epidemiological studies and meta-analyses indicate no malformative toxicity of doxylamine succinate and pyridoxine hydrochloride. Because doxylamine succinate has anticholinergic and sedative properties, caution is needed with the newborn if the mother is treated up to delivery.

Breastfeeding: can you take Doxylamine/pyridoxine?

Doxylamine passes into milk in small amounts and may cause infant drowsiness. Use cautiously during lactation or avoid.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take the evening capsule 30–60 minutes before sleep – doxylamine causes drowsiness, which here helps night sleep and reduces nausea on waking. Do not combine with alcohol or other sedatives. Morning and afternoon doses are taken as needed for persistent post-meal nausea. Sold over-the-counter in Spain and North America; prescription-only in the UK.

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Frequently asked

What is Doxylamine/pyridoxine used for?

Doxylamine/pyridoxine is evaluated for the following indications with varying evidence strength: Nausea and vomiting of pregnancy (evidence tier A), Hyperemesis gravidarum (evidence tier B), Insomnia and sleep disorders (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Doxylamine/pyridoxine?

Common side effects of Doxylamine/pyridoxine (≥ 1 in 100): Drowsiness (most common), Dry mouth, Constipation, Dizziness, Fatigue. See the Safety section for uncommon and serious reactions.

Is Doxylamine/pyridoxine safe during pregnancy?

Is Doxylamine/pyridoxine compatible with breastfeeding?

Doxylamine passes into milk in small amounts and may cause infant drowsiness. Use cautiously during lactation or avoid.

Can you drink alcohol while taking Doxylamine/pyridoxine?

Do not combine with alcohol or other sedatives.

Who should not take Doxylamine/pyridoxine?

Doxylamine/pyridoxine is contraindicated in: Hypersensitivity to doxylamine, pyridoxine, or other alkylamines; Angle-closure glaucoma; Urinary retention with BPH; Epilepsy with active seizures; Concurrent MAO inhibitors. Full list in the Safety section.

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