Evigrade
DrugsCosmetic ingredientsCalculatorsInteractionsEvigrade SkinEvigrade Meds ↗
ConditionsJournalMethodologyPro for practitioners
ESRU

Doxylamine

AEMPS

First-generation antihistamine (ethanolamine); antiemetic in combination with pyridoxine

ATC code: A04AD51

Brand names: Unisom, Diclegis, Bonjesta

Updated · Methodology

Indications

A

Nausea and vomiting of pregnancy

First line

Doxylamine 10 mg + pyridoxine 10 mg (Cariban in Spain) is first-line therapy for moderate nausea and vomiting in pregnancy. AEMPS authorises it from the first trimester; 2018 and SEGO 2023 position it on the first step after pyridoxine monotherapy. Safety is supported by 70 years of clinical experience (since 1956); meta-analyses of more than 200,000 pregnancies show no teratogenicity. Dosing: 1–2 capsules at bedtime, adding morning and afternoon doses if symptoms persist. The main adverse effect is drowsiness, so therapy starts with the evening dose.

Sources

  1. AEMPS: Ficha técnica de Doxilamina + Piridoxina (Cariban) (2023)
  2. ACOG: Practice Bulletin No. 189: Nausea and Vomiting of Pregnancy (2018)

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.

D

Insomnia and sleep disorders

Not recommended

In Spain doxylamine is sold over the counter as Dormidina, Dormirel and Soñodor for «occasional sleep disturbance». The sedative effect is real, mediated by central H1 blockade. But 2017 and SEN 2022 do not recommend first-generation antihistamines as preferred insomnia treatments: the effect on sleep onset latency is modest (10–15 minutes in meta-analyses), tolerance develops within 3–7 consecutive nights, and next-day drowsiness with impaired driving is common. The anticholinergic effect is particularly problematic in older adults – linked to an increased dementia risk with long-term use (Gray 2015, JAMA Intern Med). If doxylamine is taken as an «over-the-counter sleep aid» for more than 2 weeks, consider seeking a second opinion: insomnia responds to CBT-I, not to masking symptoms with an antihistamine.

Sources

  1. AEMPS: Ficha técnica de Doxilamina + Piridoxina (Cariban) (2023)
  2. AASM: Behavioral and psychological treatments for chronic insomnia disorder in adults (2021)

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

H1-histamine receptor blocker with marked CNS penetration. Also blocks muscarinic M1 receptors – producing anticholinergic effects (dry mouth, urinary retention, constipation). Sedation results from central H1 blockade. Combined with pyridoxine (vitamin B6) it enhances antiemetic action via several pathways: H1 blockade reduces vomiting centre activity and pyridoxine participates in synthesis of neurotransmitters regulating emesis. Half-life 10–12 hours, so morning drowsiness is common.

Safety

Contraindications

  • Hypersensitivity to doxylamine or ethanolamine antihistamines
  • Narrow-angle glaucoma
  • Prostatic hypertrophy with urinary retention
  • Age under 6 years (without prescription supervision)
  • Severe hepatic impairment
  • Concurrent MAO inhibitors
  • Breastfeeding

Serious adverse effects

  • Anticholinergic burden in older adults: confusion, delirium, falls
  • Association with dementia risk on long-term use (Gray, JAMA IM 2015)
  • Paradoxical excitation in children
  • Severe allergic reactions (rare)
  • Overdose with anticholinergic toxidrome

Common adverse effects

  • Drowsiness and sedation
  • Dry mouth
  • Constipation
  • Blurred vision
  • Urinary retention (especially in older adults)
  • Dizziness

Pregnancy: can you take Doxylamine?

FDA Category A for the doxylamine + pyridoxine combination in pregnancy nausea. The most studied antiemetic group in pregnancy – over 200,000 exposures in meta-analyses with no teratogenic signal. AEMPS and SEGO authorise use from the first trimester. The drug is continued in hyperemesis, with dose escalation up to 4 capsules per day.

Breastfeeding: can you take Doxylamine?

Not preferred. Hale L4. First-generation antihistamines suppress lactation and transfer into milk. The infant may experience drowsiness, poor sucking and irritability. eLactancia – «raised risk»; second-generation antihistamines (loratadine, cetirizine) are preferred when needed.

Calculate RID

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

Drug–nutrient interactions

Label mentions16 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • CriticalIMAOclass named in the label
    «Uso concomitante con los inhibidores de la monoaminooxidasa (IMAO), ya que se intensifican y alargan los efectos adversos de Cariban sobre el sistema nervioso central.»

    AEMPS, section 4.3 · Open on CIMA

  • Majorantiarrítmicosclass named in the label
    «Debido a que varios antihistamínicos pueden prolongar el intervalo QT, aunque no se ha observado este efecto con doxilamina, debe evitarse el uso concomitante de medicamentos que prolonguen dicho…»

    AEMPS, section 4.5 · Open on CIMA

  • Majorantipsicóticosclass named in the label
    «Debido a que varios antihistamínicos pueden prolongar el intervalo QT, aunque no se ha observado este efecto con doxilamina, debe evitarse el uso concomitante de medicamentos que prolonguen dicho…»

    AEMPS, section 4.5 · Open on CIMA

  • Majorbarbitúricosclass named in the label
    «Sedantes (barbitúricos, benzodiazepinas, antipsicóticos, analgésicos opiodes): pueden incrementar su acción hipnótica.»

    AEMPS, section 4.5 · Open on CIMA

  • Majorbenzodiazepinasclass named in the label
    «Sedantes (barbitúricos, benzodiazepinas, antipsicóticos, analgésicos opiodes): pueden incrementar su acción hipnótica.»

    AEMPS, section 4.5 · Open on CIMA

  • Majordepresores del SNCclass named in the label
    «Cariban no se recomienda cuando la mujer está tomando simultáneamente depresores del sistema nervioso central (SNC), incluido el alcohol. La combinación puede provocar somnolencia severa que conduce…»

    AEMPS, section 4.4 · Open on CIMA

  • Majordiuréticosclass named in the label
    «Debe evitarse el uso concomitante de fármacos que provoquen alteraciones electrolíticas tales como hipopotasemia o hipomagnesemia (p.ej. ciertos diuréticos).»

    AEMPS, section 4.5 · Open on CIMA

  • Majormacrólidosclass named in the label
    «Debe evitarse el uso concomitante de medicamentos inhibidores del citocromo P-450 (p. ej. derivados del azol o macrólidos).»

    AEMPS, section 4.5 · Open on CIMA

  • Majormedicamentos que prolongan el QTclass named in the label
    «Debido a que varios antihistamínicos pueden prolongar el intervalo QT, aunque no se ha observado este efecto con doxilamina, debe evitarse el uso concomitante de medicamentos que prolonguen dicho…»

    AEMPS, section 4.5 · Open on CIMA

  • Amiodarone
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

  • Amitriptyline
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

  • Captopril
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

  • Chlorpheniramine
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

  • Furosemide
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

  • Methyldopa
    «Fármacos antihipertensivos con efecto sedante sobre el SNC (especialmente alfa-metildopa), ya que pueden intensificar el efecto sedante cuando se adminisatran con antihistamínicos.»

    AEMPS, section 4.5 · Open on CIMA

  • Quinidine
    «Medicamentos fotosensibilizantes: El uso concomitante de antihistamínicos con otros agentes fotosensibilizantes como amiodarona, quinidina, imipramina, doxepina, amitriptilina, griseofulvina…»

    AEMPS, section 4.5 · Open on CIMA

Check interaction with another drug

Opens the checker prefilled with this drug. Pick the second one from your regimen.

Open checker

Summary of a multi-drug list →

Medicine list: everything you take in one place →

Frequently asked

What is Doxylamine used for?

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

What are the side effects of Doxylamine?

Common side effects of Doxylamine (≥ 1 in 100): Drowsiness and sedation, Dry mouth, Constipation, Blurred vision, Urinary retention (especially in older adults), Dizziness. See the Safety section for uncommon and serious reactions.

Is Doxylamine safe during pregnancy?

FDA Category A for the doxylamine + pyridoxine combination in pregnancy nausea. The most studied antiemetic group in pregnancy – over 200,000 exposures in meta-analyses with no teratogenic signal. AEMPS and SEGO authorise use from the first trimester. The drug is continued in hyperemesis, with dose escalation up to 4 capsules per day.

Is Doxylamine compatible with breastfeeding?

Not preferred. Hale L4. First-generation antihistamines suppress lactation and transfer into milk. The infant may experience drowsiness, poor sucking and irritability. eLactancia – «raised risk»; second-generation antihistamines (loratadine, cetirizine) are preferred when needed.

Who should not take Doxylamine?

Doxylamine is contraindicated in: Hypersensitivity to doxylamine or ethanolamine antihistamines; Narrow-angle glaucoma; Prostatic hypertrophy with urinary retention; Age under 6 years (without prescription supervision); Severe hepatic impairment. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

Granisetron, Ondansetron