Mar Vista Animal Medical Center

3850 Grand View Blvd.
Los Angeles, CA 90066




(for veterinary information only)



25 mg & 50 mg
10 mg, 12.5 mg & 30 mg
50 mg



Histamine is an inflammatory biochemical that causes skin redness, swelling, pain, increased heart rate, and blood pressure drop when enough of it binds to enough of the many "H1" receptors throughout the body. Histamine is a very important mediator of allergy in humans, hence a spectacular array of different antihistamines has proliferated. Histamine, perhaps unfortunately, is not as important a mediator of inflammation in pets which means results of antihistamine therapy are not as reliable in pets.



Diphenhydramine has several important effects and thus several uses. Most obviously, diphenhydramine is an antihistamine and it is used for acute inflammatory and allergic conditions such as:

Diphenhydramine is frequently prescribed in the treatment of itchy skin though recent evidence-based guidelines for allergic skin disease have not found it to be particularly helpful except possibly in acute reactions involving hives. It may create enough drowsiness to reduce scratching but does not seem very supportive in actually reducing itch.

See more information on the management of itchy skin.

Mast cell tumors are tumors involving cells that contain granules of histamine. Patients with mast cell tumors experience chronic inflammatory symptoms due to circulating histamine. Antihistamines such as diphenhydramine may be helpful given long term.

Diphenhydramine has a strong anti-nausea side effect that makes it helpful in treating motion sickness. This effect is "dogs only" and does not apply to cats.

Diphenhydramine causes drowsiness in animals just as it does in people and can be used as a mild tranquilizer. Given there is an anti-nauseal effect in dogs as well as a tranquilizing side effect, it can be used for traveling situations where very light effects are needed. There are stronger anti-nauseals (such as maropitant) and stronger tranquilizers (such as acepromazine).

Diphenhydramine can be given with or without food.

Diphenhydramine should be stored at room temperature, away from light.



With so many possible uses of this medication, it is difficult to separate out a side effect from a primary effect. Drowsiness is generally regarded as an undesirable side effect but in certain circumstances as mentioned, it might be the primary desired effect.

At doses higher than the recommended dose, human patients complain of dry mouth, constipation, and experience difficulty with urination.

Diphenhydramine can interfere with intradermal skin testing for allergy. Ask your veterinary dermatologist for instructions on withdrawal of this medication prior to testing.

Occasionally a cat will experience excessive excitement on diphenhydramine, necessitating confinement for everyone's safety. This is a rare side effect.



In the treatment of allergic skin disease, antihistamines are felt to synergize with omega 3 fatty acid supplements and, as a general rule for this condition, it is best to use these medications together.

Diphenhydramine should not be used with additional tranquilizing medications as the tranquilization effect can be inappropriately enhanced.

In animals that experience a hyperactivity reaction while taking metoclopramide (Reglan), this effect can be reversed with a dose of diphenhydramine.

The side effects of dry mouth, increased heart rate, and difficulty urinating are more likely when diphenhydramine is used in conjunction with a tricyclic antidepressant (such as clomipramine) or with an MAO inhibitor such as selegiline.



If a dose is accidentally skipped, do not double up on the next dose. Store at room temperature.

Be careful of oral liquids containing alcohol. These formulations should not be used in pets.

It is important to realize that the name “Benadryl” is a brand name and there are many different products sold under this name. Likewise, there are generics that include diphenhydramine that also include inappropriate ingredients. To emphasize this point, we show such a product below. It seems like it would contain diphenhydramine but, in fact, it contains a combination of diphenhydramine and other medications, including a dose of acetaminophen which could be lethal to a pet.

Never buy over-the-counter medication for your pet
without knowing exactly what you are supposed to get
and never medicate your pet without your vet’s guidance.


his product contains a combination of medications with substantial potential for harm if given to a pet.

This product contains a combination
of medications with substantial
potential for harm if given to a pet.

This product contains only Diphenhydramine, with no additional medications added.

This product contains only Diphenhydramine, with no
additional medications added.


Short version (to help us comply with "Lizzie's Law")

Page last updated: 10/10/2021