Adult: Usual dose: 10-50 mg 6 hourly as needed; 100 mg as single dose may be given if necessary. Max: 400 mg daily. Doses are given via IV inj at a rate of ≤25 mg/min or deep IM inj. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Adult: Usual dose: 10-50 mg 6 hourly as needed; 100 mg as single dose may be given if necessary. Max: 400 mg daily. Doses are given via IV inj at a rate of ≤25 mg/min or deep IM inj. Dosage recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: 5 mg/kg daily in 4 divided doses via IV inj at a rate of ≤25 mg/min or deep IM inj. Max: 300 mg daily. Dosage recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Allergic conditions
Adult: Usual dose: 25-50 mg 3 or 4 times daily. Alternatively, 25-50 mg 4-6 hourly. Max: 300 mg daily. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: 2-<6 years 6.25 mg 4-6 hourly (Max: 37.5 mg daily); 6-<12 years 12.5-25 mg 4-6 hourly (Max: 150 mg daily); ≥12 years Same as adult dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Short-term management of insomnia
Adult: 50 mg given before bedtime as needed. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: ≥12 years Same as adult dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Motion sickness
Adult: Usual dose: 25-50 mg 4-6 hourly. Max: 300 mg daily. For prevention, administer the dose 30 minutes before exposure to motion. Treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: 6-<12 years 12.5-25 mg 4-6 hourly (Max: 150 mg daily); ≥12 years Same as adult dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).
Topical/Cutaneous Pruritic skin disorders
Adult: For temporary relief of pruritus and pain associated with various skin conditions (e.g. minor burns, sunburn, minor cuts or scrapes, minor skin irritation, insect bites): As 2% gel: Apply onto the affected area(s) up to 3-4 times daily. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: ≥2 years As 2% gel: Same as adult dose.
Administration
Diphenhydramine May be taken with or without food.
Incompatibility
IV/IM inj: Incompatible with amphotericin B, cefmetazole sodium, cefalotin sodium, hydrocortisone sodium succinate, certain soluble barbiturates, certain contrast media, and strong acids or alkali solutions.
Contraindications
Neonates or premature infants (oral, IV/IM). Use of IV/IM inj as a local anaesthetic. Topical application to large areas of the body. Lactation (IV/IM). Concomitant use of topical preparations with other formulations that contain diphenhydramine (including oral). Contraindications may vary among countries and between individual products (refer to specific product guidelines).
Special Precautions
Patient with prostatic hyperplasia or hypertrophy, bladder neck obstruction, urinary retention, respiratory conditions (e.g. asthma, bronchitis, emphysema), narrow-angle glaucoma or increased IOP, stenosing peptic ulcer, pyloroduodenal obstruction, CV disease (e.g. hypertension, ischaemic heart disease), thyroid dysfunction, myasthenia gravis, epilepsy or seizure disorder. Moderate to severe renal and hepatic impairment. Children and elderly. Pregnancy; lactation (oral).
Adverse Reactions
Significant: CNS depression (e.g. daytime drowsiness, sedation, fatigue, lack of concentration, memory impairment), anticholinergic effects (e.g. blurred vision, dry mouth, urinary retention, tachycardia, constipation, agitation, cognitive dysfunction, delirium); drug tolerance (continuous use for insomnia). Blood and lymphatic system disorders: Agranulocytosis, haemolytic anaemia, thrombocytopenia. Cardiac disorders: Palpitations, extrasystoles. Gastrointestinal disorders: Nausea, vomiting, epigastric distress. General disorders and administration site conditions: Chills. Metabolism and nutrition disorders: Anorexia. Nervous system disorders: Dizziness, unsteadiness, headache, paraesthesia, convulsion, tremor. Psychiatric disorders: Paradoxical excitation (e.g. increased energy, nervousness, restlessness), sleep disturbances, depression. Renal and urinary disorders: Urinary difficulty, urinary frequency. Respiratory, thoracic and mediastinal disorders: Thickening of bronchial secretions, nasal congestion, wheezing, chest tightness. Skin and subcutaneous tissue disorders: Sensitisation reaction, photosensitivity, hyperhidrosis. Vascular disorders: Hypotension.
This drug may cause drowsiness, dizziness or blurred vision, if affected, do not drive or operate machinery. Topical: Discontinue use and inform your doctor if your condition worsens or no improvement is observed within 7 days, or if symptoms clear up and occur again within a few days.
Management: Supportive and symptomatic treatment. Administer parenteral diazepam for the treatment of convulsions and marked CNS stimulation.
Drug Interactions
May enhance the sedative effects of other CNS depressants (e.g. anxiolytics, hypnotics, tranquillisers). May potentiate the effects of anticholinergic agents (e.g. atropine) or TCAs. Prolonged and enhanced anticholinergic effects with MAOIs.
Food Interaction
May enhance the sedative effect of alcohol.
Lab Interference
May suppress wheal and flare reactions to skin test antigens. May give false-positive results in urine detection of methadone and phencyclidine and screening of serum TCA.
Action
Description: Mechanism of Action: Diphenhydramine is a monoethanolamine derivative, 1st generation antihistamine with anticholinergic and marked sedative properties. It acts by competing with histamine for the H1-receptors on effector cells in the gastrointestinal tract, blood vessels and respiratory tract. Duration: Histamine-induced wheal suppression: ≤10 hours; histamine-induced flare suppression: ≤12 hours. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: 42-62%. Time to peak plasma concentration: Approx 1-4 hours. Distribution: Widely distributed throughout the body, including CNS. Crosses the placenta and enters breast milk. Volume of distribution: 17 L/kg. Plasma protein binding: Approx 80-85%. Metabolism: Extensively metabolised in the liver by CYP2D6 via N-demethylation and minor demethylation by CYP1A2, CYP2C9 and CYP2C19; undergoes significant first-pass metabolism. Excretion: Mainly via urine (as metabolites; <4% as unchanged drug). Elimination half-life: 2.4-9.3 hours.
Chemical Structure
Diphenhydramine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3100, Diphenhydramine. https://pubchem.ncbi.nlm.nih.gov/compound/Diphenhydramine. Accessed Sept. 25, 2025.
Storage
Oral: Tab/Cap/Oral solution or syrup: Store below 25°C.
Parenteral: IV/IM inj: Store between 20-25°C. Protect from light and freezing.
Topical: Cream or gel: Store at room temperature.
Storage recommendations may vary among countries and between individual products. Refer to specific product guidelines.
R06AA02 - diphenhydramine ; Belongs to the class of aminoalkyl ethers used as systemic antihistamines. D04AA32 - diphenhydramine ; Belongs to the class of topical antihistamines used in the treatment of pruritus.
References
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