Skip to Main Content


  1. Pharmacology. Diphenhydramine is an antihistamine with anticholinergic, antitussive, antiemetic, and local anesthetic properties. The antihistaminic property affords relief from itching and minor irritation caused by plant-induced dermatitis and insect bites, and when used as pretreatment, it provides partial protection against anaphylaxis caused by animal serum-derived antivenoms or antitoxins. Drug-induced extrapyramidal symptoms respond to the anticholinergic effect of diphenhydramine. The effects of diphenhydramine are maximal at 1 hour after intravenous injection and last up to 7 hours. The drug is eliminated by hepatic metabolism, with a serum half-life of 3–7 hours.

  2. Indications

    1. Relief of symptoms caused by excessive histamine effect (eg, ingestion of scombroid-contaminated fish or niacin and rapid intravenous administration of acetylcysteine). Diphenhydramine may be combined with cimetidine or another histamine 2 (H2) receptor blocker.

    2. Pretreatment before administration of animal serum-derived antivenoms or antitoxins, especially in patients with a history of hypersensitivity or with a positive skin test. Diphenhydramine can be combined with cimetidine or another H2 receptor blocker.

    3. Neuroleptic drug-induced extrapyramidal symptoms and priapism (one case report).

    4. Pruritus caused by poison oak, poison ivy, or minor insect bites.

  3. Contraindications

    1. Angle-closure glaucoma.

    2. Prostatic hypertrophy with obstructive uropathy.

    3. Concurrent therapy with monoamine oxidase inhibitors.

  4. Adverse effects

    1. Sedation, drowsiness, and ataxia may occur. Paradoxical excitation is possible in small children.

    2. Excessive doses may cause flushing, tachycardia, blurred vision, delirium, toxic psychosis, urinary retention, and respiratory depression.

    3. Some preparations may contain sulfite preservatives, which can cause allergic-type reactions in susceptible persons.

    4. Diphenhydramine may exacerbate dyskinetic movement disorders as a result of increased dopamine (eg, amphetamine or cocaine intoxication) or decreased cholinergic effects in the CNS.

    5. Extravasation from an IV dose of 500 mg into arm soft tissue resulted in a chronic regional pain syndrome (case report). Local necrosis from subcutaneous route.

    6. Use in pregnancy. FDA Category B (Introduction). Fetal harm is extremely unlikely.

  5. Drug or laboratory interactions

    1. Additive sedative effect with opioids, ethanol, and other sedatives.

    2. Additive anticholinergic effect with other antimuscarinic drugs.

  6. Dosage and method of administration

    1. Pruritus. Give 25–50 mg PO every 4–6 hours (children: 5 mg/kg/d in divided doses; usual oral doses for ages 6–12 years are 12.5–25 mg every 4–6 hours, and for ages 2–6 years, they are 6.25 mg every 4–6 hours); maximum daily dose: 37.5 mg (children aged 2–6 years), 150 mg (children aged 6–12 years), and 300 mg (adults). The drug may also be applied topically, although systemic absorption and toxicity have been reported, especially when it is used on large areas with blistered or broken skin.

    2. Pretreatment before antivenom administration. Give 50 mg (children: 0.5–1 mg/kg) IV; if possible, it should be given at least 15–20 minutes before antivenom use. Rate of IV administration should not exceed 25 mg/min.

    3. Drug-induced extrapyramidal symptoms. Give 50 mg (children: 0.5–1 mg/kg) IV (at a rate not to exceed 25 mg/min) or deep IM; if there is no response within 30–60 minutes, repeat dose to a maximum of 100 mg (adults). Provide oral ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.