Diphenhydramine

By Lauren R. Forsythe, PharmD, MBA, DICVP; Rania Gollakner, BS, DVM, MPH

What is diphenhydramine?

Diphenhydramine (brand name: Benadryl®, Vetadryl®, Banophen®, Genahist®, Diphenhist®, Unisom®, Sominex®) is an antihistamine used in cats, dogs, ferrets and other small mammals, birds, horses, and cattle to treat allergic reactions, motion sickness, and vomiting. It is also used as a mild sedative and is one of the therapies for mast cell tumors.

Its use in small and large animals to treat allergic reactions and other conditions is “off label” or “extra label”. Many drugs are commonly prescribed for off-label use in veterinary medicine. In these instances, follow your veterinarian’s directions and cautions carefully, as they may be significantly different from those on the label.

How is diphenhydramine given?

  • Diphenhydramine is given by mouth in the form of a tablet, capsule, oral liquid, or liquid injection. 
  • The oral formulations can be given with or without food. If your pet vomits after dosing on an empty stomach, give future doses with food or a treat. 
  • The liquid has a bad taste to cats, and administration by mouth may be difficult. 
  • The injection is typically given in the hospital, in the vein, muscle, or under the skin.

This medication will take effect quickly, in about 1 to 2 hours, and improvement in clinical signs should follow.

What if I miss giving my pet the medication?

If you miss a dose, give it as soon as you remember, and then continue with the regular dosing schedule. However, if it is almost time for the next dose, skip the missed dose and resume the regular dosing schedule. Do not give the pet two doses at once.

Are there any potential side effects?

Diphenhydramine may cause the following side effects:

  • lethargy
  • excitement (especially in cats)
  • dry mouth
  • urinary retention
  • vomiting
  • diarrhea
  • lack of appetite

Diphenhydramine can alter the results of skin allergy testing; discontinue this medication at least 2 weeks before testing. This short-acting medication should stop working within 24 hours, although effects can be longer in pets with liver or kidney disease.

Are there any risk factors for this medication?

Diphenhydramine should NOT BE USED in:

  • pets that are allergic to it or similar antihistamines
  • pediatric or neonatal pets

Diphenhydramine should be USED WITH CAUTION in pets that:

  • have glaucoma
  • have prostate enlargement
  • have intestinal or bladder obstruction
  • have chronic obstructive pulmonary disease (COPD)
  • have elevated thyroid hormone
  • have heart disease
  • have high blood pressure
  • are pregnant or lactating
  • are geriatric 
  • are working dogs

Are there any drug interactions I should be aware of?

Be sure to tell your veterinarian about any medications (including vitamins, supplements, or herbal therapies) that your pet is taking. The following medications should be USED WITH CAUTION when given with diphenhydramine:

  • anticholinergic drugs
  • tricyclic antidepressants 
  • central nervous system (CNS) depressants such as sedatives, anesthetics, and pain medications

Is there any monitoring that needs to be done with this medication?

  • No specific monitoring is required while your pet is taking this medication. 
  • Your veterinarian may monitor your pet to be sure that the medication is working. 
  • Monitor your pet at home for adverse effects.

How do I store diphenhydramine?

  • All formulations of diphenhydramine should be stored at room temperature, between 15°C and 30°C (59°F to 86°F) and protected from light. 
  • Oral liquids should be protected from freezing.

What should I do in case of emergency?

If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. If they are not available, follow their directions in contacting an emergency facility.

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