First-generation sedating antihistamine
Updated · Methodology
Second line
Urticaria and acute allergic reaction. Per 2022 – second-line after non-sedating 2nd-generation H1-blockers. Used for severe acute reactions or angioedema, 25–50 mg orally or IM up to 4 times daily. Long-term use not recommended due to sedation and anticholinergic effects.
Sources
ICD-10: L50 · ICD-11: EB05
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Diphenhydramine while breastfeeding. RID about 1%, Hale L2. A single low dose is safe. Repeated high doses may theoretically reduce milk supply (anticholinergic) and cause infant drowsiness. Prefer loratadine (Hale L1) or cetirizine.
Sources
ICD-10: T78.4 · ICD-11: 4A8Z
Blocks H1 histamine receptors. Crosses BBB, causes marked sedation. Anticholinergic activity explains dry mouth and urinary retention in elderly. Used in acute allergic reactions, short-term insomnia, motion sickness.
Safe when indicated. Long-term high-dose use in 3rd trimester – withdrawal and paradoxical excitation in newborn.
Compatible with caution. Hale L2. RID about 1%. Single dose – safe. Repeated use risks milk supply reduction and infant drowsiness. Prefer loratadine, cetirizine.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«Potential for Other Drugs to Affect Clozapine: Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine…»FDA, section 7 · Open on DailyMed
«Metoprolol es un sustrato del CYP2D6. Los fármacos que inhiben el CYP2D6 pueden tener un efecto en la concentración plasmática de metoprolol. Ejemplos de fármacos que inhiben CYP2D6 son quinidina…»AEMPS, section 4.5 · Open on CIMA
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Summary of a multi-drug list →
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Diphenhydramine is evaluated for the following indications with varying evidence strength: Urticaria (evidence tier B), Allergy during breastfeeding (evidence tier C). See the full indication matrix with dosing and citations above on this page.
Common side effects of Diphenhydramine (≥ 1 in 100): Drowsiness, Dry mouth, Constipation, Urinary retention, Dizziness. See the Safety section for uncommon and serious reactions.
Safe when indicated. Long-term high-dose use in 3rd trimester – withdrawal and paradoxical excitation in newborn.
Compatible with caution. Hale L2. RID about 1%. Single dose – safe. Repeated use risks milk supply reduction and infant drowsiness. Prefer loratadine, cetirizine.
Do not combine with alcohol, benzodiazepines, opioids – additive sedation.
Diphenhydramine is contraindicated in: Hypersensitivity; Narrow-angle glaucoma; Prostatic hypertrophy with urinary retention; Stenosing GI ulcer; Age <2 years. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Doxylamine/pyridoxine, Ebastine, Fexofenadine, Ketotifen, Loratadine, Bilastine, Chlorpheniramine, Levocetirizine