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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

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

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.

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.

References

References

Textbooks & handbooks

  • Plumb, D.C. Plumb's Veterinary Drug Handbook. 10th ed., Wiley-Blackwell, 2023.
  • Vail, D.M., Thamm, D.H., & Liptak, J.M. (eds.). Withrow & MacEwen's Small Animal Clinical Oncology. 6th ed., Saunders/Elsevier, 2020.
  • Riviere, J.E., & Papich, M.G. (eds.). Veterinary Pharmacology and Therapeutics. 10th ed., Wiley-Blackwell, 2018.
  • National Research Council. Nutrient Requirements of Dogs and Cats. National Academies Press, Washington DC, 2006.
  • The Merck Veterinary Manual. Merck & Co., Online edition. https://www.merckvetmanual.com/

Clinical guidelines & consensus

  • Fletcher, D.J., Boller, M., Brainard, B.M., et al. "RECOVER Evidence and Knowledge Gap Analysis on Veterinary CPR." Journal of Veterinary Emergency and Critical Care, 2012;22(S1):S102–S131.
  • American Animal Hospital Association. 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. AAHA Press.

Journals & peer-reviewed studies

  • Hogan, D.F., Fox, P.R., Jacob, K., et al. "Secondary prevention of cardiogenic arterial thromboembolism in the cat: The FAT CAT study." Journal of Veterinary Cardiology, 2015;17(Suppl 1):S306–S317.
  • Boswood, A., Häggström, J., Gordon, S.G., et al. "Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study — A Randomized Clinical Trial." Journal of Veterinary Internal Medicine, 2016;30(6):1765–1779.
  • ASPCA Animal Poison Control Center. Toxicology and Poison Management Guidelines. American Society for the Prevention of Cruelty to Animals. https://www.aspca.org/pet-care/animal-poison-control

Regulatory & approvals

  • Central Drugs Standard Control Organisation (CDSCO), Government of India. Veterinary Drug Approval Registry, 1969–2026. Directorate General of Health Services. https://cdsco.gov.in/

Databases

  • Washington State University, College of Veterinary Medicine. Veterinary Clinical Pharmacology Laboratory (VCPL) — MDR1 Multidrug Sensitivity Database. https://vcpl.vetmed.wsu.edu/
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 →

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