Today in the following article, I decided to discuss two highly effective drugs Simplicef and Benadryl, their benefits, dosage, interactions, and side effects for dogs, cats, and all types of canine and feline species. Simplicef is an antibiotic while Benadryl is an anti-allergic or anti-histamine medication. It’s important to know about their indications, interactions, and dose to avoid serious complications.

Simplicef is the trademark of the Pfizer pharmaceutical company. Its generic name is Cefpodoxime proxetil, which belongs to the cephalosporin class of antibiotic drugs. Cephalosporins treat bacterial infections by stopping the mechanism of cell wall synthesis of bacterial cells. So, they are effective against almost all types of gram-positive and gram-negative types of bacteria.


If a dog has developed a bacterial infection of the skin, urinary tract, nose/eye, or ear, etc. Then, you don’t need to worry because the cefpodoxime proxetil medication can treat all kinds of infectious diseases in dogs (caused by bacteria that contain a cell wall).

Benadryl on the other hand used to treat allergic reactions in dogs and other living organisms. It contains a chemical ingredient called “diphenhydramine” which is used to treat skin rashes, runny nose, pain, itching, burns, and other allergic conditions.

Simplicef and Benadryl Together For Dogs

But the question is “Can We Use Simplicef And Benadryl Together?“. So, the answer is a little complicated because there are not any side effects or adverse reactions found when the cefpodoxime proxetil and diphenhydramine are given together. But to avoid drug interaction, it is advised that you should never use them together in the following cases described below;

  • In pregnant dogs, it is suggested to avoid taking cefpodoxime and diphenhydramine medication together. But a veterinarian may take a decision whether it is necessary or not. 
  • Nursing or lactating dogs.
  • Dogs with a history of kidney disease.
  • A dog with any liver illness.
Although, both drugs are FDA approved and can be used in dogs together. A veterinarian may decide whether to prescribe them together or not. But it’s suggested to avoid them during the pregnancy period, lactation, and others shown in the above list. If you’re using Simplicef and Benadryl together for your dog, then there should be, at least, one hour difference between their doses.

What Does Benadryl Treats In Dogs?

Benadryl contains an anti-histamine drug called “Diphenhydramine Hydrochloride”. This drug helps to treat all kinds of allergic reactions in dogs. It can provide relief from the following conditions;

  • Itching 
  • Skin rashes
  • Burns
  • Itching due to insect bites
  • Insect bites allergic reactions like rashes, itching, hair loss, etc
  • Heat rashes (as it is also available in topical cream/spray form)
  • Runny nose
  • Hives
  • Nasal congestion
  • Sneezing
  • Swelling or inflammation 
  • Redness of skin
It can also be used other allergic reactions that are not described above. Your dog’s veterinarian would decide whether to use it or not. It does not treat bacterial infections or kill bacteria. You have to take an antibiotic drug if your dog has developed any type of bacterial infection.


Benadryl (diphenhydramine HCl) is available for your dog in the following forms;
  • Topical cream
  • Topical spray
  • Chewable tablets
  • Liquid oral suspension
  • Cooling gel form to prevent itching instantly
  • Itch relief stick form


If you want to know the ideal dosage plan for your dog for itching, skin rashes, runny nose, or any other allergic reaction. You have to consult your veterinarian. Because it’s a prescription drug and is not available without a valid veterinarian prescription. 
However, you can use Benadryl extra strength cooling gel, stick, and topical cream or spray for your dog. You have to just apply an adequate amount of cream/spray/gel on the affected area. But when we talk about chewable tablets or liquid suspension or drops, you have to ask your veterinarian. 

Side Effects Or Adverse Reactions

However it’s a highly tolerable drug, but may not be suitable for some dogs. The dogs who are hypersensitive to diphenhydramine or other anti-histamine drugs i.e, loratadine, etc should avoid this drug. Immediately stop using this drug, if you see the following adverse reactions after consuming;
  • Vomiting
  • Diarrhea
  • Nausea
  • Upset stomach
  • Abdominal pain
  • Constipation
  • Abdominal cramps
  • Loss of appetite (anorexia)
  • Increased thirst or drinking more water
  • Change in behavior i.e, aggressiveness, barking, anxiousness, etc

Usually, diphenhydramine does not show adverse reactions but if you see any of the above by using this drug, immediately re-visit your dog’s veterinarian and consult about the situation. 

What Does Simplicef Treats In Dogs?

It contains an antibacterial ingredient called “Cefpodoxime proxetil” is a third-generation cephalosporin, a strong antibiotic drug, that is FDA (Food and Drug Administration) approved drug to treat a broad range of bacterial diseases in pets
It’s available in film-coated tablets, which are provided in two strengths i.e, 100mg and 200mg.  A veterinarian may suggest the ideal dose for a dog but of 2.3milligram to 4.5milligram per one pound (lb) is the recommended dose for dogs.
Cefpodoxime can be used to treat the following problems;
  • Urinary tract infections including bladder, ureters, urethra, and kidneys infection caused a bacterial accumulation.
  • Bacterial infections of the nose, ear, and eyes
  • Periodontal disease (swollen gums or other dental infections)
  • Sore throat
  • Skin bacterial diseases include folliculitis, cellulitis, pyoderma, and others.
  • Paw infection 
  • All types of soft tissue infections
  • Wounds
  • Abscesses
  • Burns
  • Secondary infections are caused by viruses, parasites, and insect bites.


You can give your dog Benadryl (diphenhydramine HCL) with Simplicef (cefpodoxime proxetil) together but avoid if your dog is pregnant, nursing, or lactating, or has a history of kidney or liver ailment. Diphenhydramine (anti-allergy drug) treats all types of allergic conditions in dogs including itchiness, burns, skin rashes, runny nose, sneezing, and others not described here. Simplicef contains an active ingredient “cefpodoxime proxetil“, which is an antibiotic drug, which is effective against a broad range of gram-positive and gram-negative types of bacteria. Both cefpodoxime and diphenhydramine can be used together to treat bacterial and allergic problems in dogs, cats, and other small animals.
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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