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Diphenhydramine

First-generation antihistamine (H1 receptor antagonist)
Last reviewed 21 Apr 2026 · PetCare.AI Editorial Team
Species
Dog, Cat
Brands
4 available
Interactions
2 documented
Formulations
4

Mechanism of action

Competitively blocks H1 histamine receptors on effector cells, preventing histamine-mediated vasodilation, increased vascular permeability, and pruritus; also has anticholinergic, antitussive, and mild sedative properties

At a glance

Class
First-generation antihistamine (H1 receptor antagonist)
Schedule
OTC
Storage
Below 25°C, protect from light

Dosing

🐕

Dog

Allergic reactions, pruritus, motion sickness, vaccine reactions, mast cell tumor premedication
Dose
1–4 mg/kg
Route
PO, IM, IV (slow)
Frequency
BID to TID
Max dose
100 mg/dose; 300 mg/day
Duration: As needed; 7–14 days for allergic dermatitis
🐈

Cat

Allergic reactions, pruritus, pre-treatment for transfusion reactions
Dose
1–4 mg/kg
Route
PO, IM
Frequency
BID to TID
Max dose
25 mg/dose; 75 mg/day
Duration: As needed; short-term preferred
Educational reference only
This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

Formulations

💊

Capsule — 1

Strength
25mg
Available in India
💊

Tablet — 1

Strength
50mg
Available in India
💉

Injectable solution — 1

Strength
50mg/mL
Available in India
🧴

Oral liquid — 1

Strength
12.5mg/5mL
Available in India

Storage

Below 25°C, protect from light

Safety

Use with caution

  • Angle-closure glaucoma
    Anticholinergic effect may increase IOP
  • Urinary obstruction
    Anticholinergic effect may worsen retention
  • Concurrent CNS depressants
    Additive sedation

Adverse effects

Common
Sedation/drowsiness
Dry mouth
Urinary retention
Serious
Paradoxical excitation (cats)
Seizures (overdose)
Anticholinergic toxicity

Monitoring parameters

Level of sedationAllergic symptom resolutionGI motility
Educational reference only
This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

Interactions

Moderate — 2

Acepromazine
moderate
Both cause CNS depression and have anticholinergic activity. Additive sedation and hypotension.
Management: Reduce doses. Monitor sedation level.
Tramadol
moderate
Additive CNS depression. Diphenhydramine also weakly inhibits serotonin reuptake — theoretical additive serotonergic effect with tramadol.
Management: Monitor sedation. Usually well-tolerated at standard doses.
Educational reference only
This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

Brands

International

Benadryl
Johnson & Johnson
Vetadryl
Lloyd Laboratories

India

Benadryl
Johnson & Johnson India
Diph-Aid
Mankind Pharma

FAQs

Frequently asked questions

›What is Diphenhydramine?
Diphenhydramine is a first-generation antihistamine (h1 receptor antagonist) used in pets. Competitively blocks H1 histamine receptors on effector cells, preventing histamine-mediated vasodilation, increased vascular permeability, and pruritus; also has anticholinergic, antitussive, and mild sedative properties
›What is Diphenhydramine used for in pets?
Diphenhydramine is used in veterinary medicine for: Allergic reactions, pruritus, motion sickness, vaccine reactions, mast cell tumor premedication; Allergic reactions, pruritus, pre-treatment for transfusion reactions.
›What is the Diphenhydramine dose for dogs?
For dogs, Diphenhydramine is typically dosed as follows — Allergic reactions, pruritus, motion sickness, vaccine reactions, mast cell tumor premedication: 1–4 mg/kg PO/IM/IV (slow) BID to TID. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.
›What is the Diphenhydramine dose for cats?
For cats, Diphenhydramine is typically dosed as follows — Allergic reactions, pruritus, pre-treatment for transfusion reactions: 1–4 mg/kg PO/IM BID to TID. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.
›What are the side effects of Diphenhydramine?
Common: Sedation/drowsiness, Dry mouth, Urinary retention. Serious (call your vet immediately): Paradoxical excitation (cats), Seizures (overdose), Anticholinergic toxicity.
›Does Diphenhydramine need a prescription?
Diphenhydramine is available over the counter. Even so, you should consult your veterinarian before giving any medication to your pet.
Educational reference only
This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

References

References

The PetCare.AI drug reference is built from 13 authoritative sources cited across 580 drug monographs.

Textbooks & handbooks — 5

  • Plumb's Veterinary Drug Handbook
  • Withrow & MacEwen's Small Animal Clinical Oncology
  • Merck Veterinary Manual
  • NRC Nutrient Requirements of Dogs and Cats
  • Veterinary Pharmacology and Therapeutics (Riviere & Papich)

Clinical guidelines & consensus — 4

  • ASPCA Animal Poison Control Center Guidelines
  • AAHA Diabetes Management Guidelines
  • ASPCA Poison Control Guidelines
  • RECOVER CPR Guidelines

Journals & peer-reviewed studies — 2

  • EPIC Study (J Vet Intern Med 2016)
  • JVIM FAT CAT Study

Regulatory & approvals — 1

  • CDSCO Veterinary Drug Approval Registry (1969–2026)

Databases — 1

  • Washington State University VCPL MDR1 Database

Related medicines

Other medicines in the same class (First-generation antihistamine).

Chlorpheniramine
Competitively blocks histamine H1 receptors, reducing allergic symptoms including pruritus, urticaria, and oedema; crosses the blood-brain barrier causing sedation
dogcat
Clemastine
Competitive H1-receptor antagonist that blocks histamine-mediated vasodilation, increased vascular permeability, and pruritus. Moderate anticholinergic and sedative properties.
dogcat
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