Diphenhydramine: veterinary dose and monograph

At a glance

Drug class

Veterinary drug

Also known as

Benadryl, Dimedrol

Species with doses

Dogs, Cats, Cattle, Horses, Rabbits, Ferrets and Primates

General dose range

1–4 mg/kg PO q8–12h — check the species tables for the indication

Routes

PO, IM

Last reviewed

1 October 2026

Indications

• Allergic pruritus / urticaria, atopy (adjunct)
• Pre-treatment for mast-cell-tumour handling / transfusion / vaccine reactions
• Motion sickness / mild travel sedation

Diphenhydramine dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Antihistamine / mild sedation: Plumb’s p.420: 2–4 mg/kg PO q8–12h (Papich 2000); 2.2 mg/kg PO two to three times daily; atopic dermatitis 25–50 mg per dog PO three times daily; motion sickness 2–4 mg/kg PO or IM q8h. Papich 5e: 2.2 mg/kg q8–12h PO, IM or SC (25–50 mg per large dog).
• Pre-medication for MCT handling / reaction (parenteral): Plumb’s p.420: 1 mg/kg IM, SC or IV q8–12h, not exceeding 40 mg total (Papich 2000); urticaria/angioedema 2 mg/kg IM twice daily; doxorubicin anaphylaxis 3–4 mg/kg IM with dexamethasone. Papich 5e: 2.2 mg/kg IM or SC. Give IV slowly — rapid IV can cause hypotension.

Cats

• Antihistamine: Papich 5e: 2–4 mg/kg q6–8h PO, or 1 mg/kg q8h IV or IM. Plumb’s p.420: 2–4 mg/kg PO q8h (Scherk 2006); lower regimens 0.5 mg/kg PO q12h (Messinger) or 2–4 mg per cat q12–24h (Hnilica). The liquid is distasteful to cats.

Cattle

• Anaphylaxis adjunct: Plumb’s p.420 (Clark 1986): 0.5–1 mg/kg IM or IV with epinephrine and corticosteroids. Papich 5e: 0.5–1 mg/kg IM. Extra-label — obtain a FARAD withdrawal.

Horses

• Anaphylaxis adjunct: Plumb’s p.420 (Evans 1996): 0.25–1 mg/kg IV or IM. Papich 5e (large animals): 0.5–1 mg/kg IM as a single dose as needed. Allergic skin disease: 0.75–2 mg/kg PO q12h (Rees; Miller). ARCI Class 3.

Buffalo

No buffalo-specific doses are on file, so buffalo are dosed as cattle.

• Anaphylaxis adjunct: Plumb’s p.420 (Clark 1986): 0.5–1 mg/kg IM or IV with epinephrine and corticosteroids. Papich 5e: 0.5–1 mg/kg IM. Extra-label — obtain a FARAD withdrawal.

Rabbits

• Antihistamine: Plumb’s p.420 (Morrisey & Antinoff 2003): rabbits 1–2 mg/kg PO twice daily.

Ferrets

• Pre-vaccination (prevent anaphylaxis): Plumb's p.421 (Williams 2000): 2 mg/kg PO, IM or IV given ~10 minutes before vaccination. Ferrets are prone to vaccine anaphylaxis — pre-treatment is routine.

Primates

• Antihistamine (monkeys, lemurs): Carpenter Exotic Animal Formulary 6th ed, Table 13-7 (p.705): monkeys/lemurs 5 mg/kg/day PO/IM/IV divided q6–8h; chimpanzees 25–50 mg/animal PO/IM/IV q6–8h.

Contraindications

Caution in glaucoma, urinary retention, prostatic disease and significant cardiac disease. Additive CNS depression with other sedatives. Avoid the rapid IV route (hypotension); IM is preferred for parenteral use.

Adverse effects

• Sedation, lethargy
• Anticholinergic: dry mouth, urinary retention, GI slowing
• Paradoxical excitement (occasional, especially cats)

Drug interactions

• Additive CNS depression with other sedatives / opioids / anaesthetics
• Additive anticholinergic effects with atropine-like drugs
• Blunts the wheal of intradermal allergy testing — withdraw before testing
• Monoamine-oxidase inhibitors: intensified anticholinergic effects

Pregnancy and lactation

Regarded as relatively safe and used where antihistamine therapy is needed, but use only if required.

Monitoring

• Sedation level and demeanour
• Heart rate; urination (anticholinergic retention)

Toxicity and overdose

Overdose: initial CNS depression or paradoxical excitation, anticholinergic signs (mydriasis, dry mucous membranes, urinary retention, ileus), tachycardia and, in large ingestions, seizures.

Management: Supportive — control seizures (diazepam), manage tachyarrhythmia, IV fluids and cooling; physostigmine may reverse severe central anticholinergic toxicity under monitoring. Decontaminate recent large ingestions.

Clinical pearls

• Antihistamines work best as prevention — give before the allergen / mast-cell handling, not after histamine is already released
• Give IM rather than fast IV; rapid intravenous injection can drop blood pressure
• Use a plain diphenhydramine product — combination cold remedies often contain toxic decongestants or paracetamol

Mechanism of action

First-generation H1-antihistamine. Competitively blocks histamine H1 receptors to reduce the vasodilation, oedema and pruritus of allergic responses; its lipophilicity allows CNS penetration (sedation, antiemetic / anti-motion-sickness effect) and it has anticholinergic activity.

Formulations and products

• Diphenhydramine 25 mg tablet / capsule
• Diphenhydramine 50 mg/mL injection
• Diphenhydramine 2.5 mg/mL elixir
• Benadryl — 25 / 50 mg capsule; syrup, Capsule / syrup (human-label)

Storage

Store at 15–30 °C; protect elixir / injection from light.

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

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Frequently asked questions