In today’s article, I will discuss two highly effective drugs, Simplicef and Benadryl, exploring their benefits, dosage, interactions, and side effects for dogs, cats, and various canine and feline species.


What Is Simplicef?

Simplicef, an antibiotic, is the trademark of Pfizer pharmaceuticals, and its generic name is Cefpodoxime proxetil, belonging to the cephalosporin class of antibiotics. Cephalosporins treat bacterial infections by inhibiting the synthesis of bacterial cell walls, making them effective against both gram-positive and gram-negative bacteria.

If a dog has a bacterial infection of the skin, urinary tract, respiratory tract, nose/eye, or ear, Cefpodoxime proxetil can effectively treat these infectious diseases caused by bacteria with a cell wall.

What Is Benadryl?

On the other hand, Benadryl, an anti-allergic or anti-histamine medication, contains the chemical ingredient “diphenhydramine,” used to treat various allergic conditions in dogs, such as skin rashes, runny nose, pain, itching, burns, and more.

Simplicef & Benadryl Together

The question arises: “Can we use Simplicef and Benadryl together?


While no side effects or adverse reactions have been found when Cefpodoxime proxetil and diphenhydramine are given together, it is advised to avoid combining them in certain cases:

  • In pregnant dogs (a veterinarian may decide if necessary).
  • Nursing or lactating dogs.
  • Dogs with a history of kidney disease.
  • Dogs with any liver illness.

Both drugs are FDA-approved, and their combined use in dogs should be determined by a veterinarian, with special attention to the listed conditions. If using Simplicef and Benadryl together, ensure at least a one-hour difference between their doses.

Benadryl’s Treatment for Dogs

Benadryl, containing the anti-histamine drug “Diphenhydramine Hydrochloride,” treats various allergic reactions in dogs, providing relief from conditions such as;

  • itching
  • skin rashes
  • burns
  • insect bites
  • runny nose
  • hives
  • nasal congestion
  • sneezing
  • swelling or inflammation
  • and redness of the skin

Benadryl is available in various forms, including topical cream, spray, chewable tablets, liquid oral suspension, cooling gel, and itch relief stick.


Benadryl Dosage

The ideal dosage plan for Benadryl should be consulted with a veterinarian, as it is a prescription drug not available without a valid veterinarian prescription. Chewable tablets, liquid suspension, or drops require specific veterinary guidance.

Benadryl Side Effects

While generally well-tolerated, some dogs may not respond well to Benadryl, especially those hypersensitive to diphenhydramine. Adverse reactions may include;

  • vomiting
  • diarrhea
  • nausea
  • upset stomach
  • abdominal pain
  • constipation
  • abdominal cramps
  • loss of appetite
  • increased thirst or changes in behavior

Consult your dog’s veterinarian if any of these reactions occur.

Simplicef’s Treatment for Dogs

Simplicef, containing “Cefpodoxime proxetil,” is a third-generation cephalosporin, an FDA-approved antibiotic effective against a broad range of bacterial diseases in pets.

Available in film-coated tablets of 100mg and 200mg strengths, the recommended dose is 2.3mg to 4.5mg per pound. Simplicef treats urinary tract infections, bacterial infections of the nose, ear, and eyes, periodontal disease, sore throat, skin bacterial diseases, paw infections, soft tissue infections, wounds, abscesses, burns, and secondary infections caused by viruses, parasites, and insect bites.


Simplicef (Cefpodoxime proxetil) and Benadryl (Diphenhydramine HCL) can be used together for dogs, but caution is advised in pregnant, nursing, or lactating dogs, or those with a history of kidney or liver ailments.

Benadryl treats a variety of allergic conditions, while Simplicef is effective against a broad spectrum of bacteria. Both drugs, when used together, can address bacterial and allergic problems in dogs, cats, and other small animals under the guidance of a veterinarian.

Categories: Simplicef

Doctor Xeeshan

Doctor Xeeshan

I am Doctor Xeeshan, located in Lahore, Punjab, Pakistan. In this blog, I am providing authentic information about dog breeds, diseases, medications, etc.


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