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Hi. Welcome to Just Answer. My name is***** and I've been a veterinarian for 15 years. Thank you for your question. Here is the excerpt from Plumb's Veterinary Drug Formulary: "Cefpodoxime is contraindicated in patients hypersensitive to it or other cephalosporins. Because cefpodoxime is excreted by the kidneys, dosages and/or dosage frequency may need to be adjusted in patients with significantly diminished renal function. Use with caution in patients with seizure disorders." So, it may lower the seizure threshold to some degree. The exact amount is unknown. In a situation with a stubborn UTI, it may be of benefit to do a culture and sensitivity to make sure the correct antibiotic is being used. Also it may be beneficial to take x-rays to make sure no stones are present.
So when using Simplicef in a situation with a patient that has epilepsy, the benefits have to outweigh the risks of it. It would seem that the risks are pretty minimal, but when veterinarians use it in situations like this they need warn clients about possible breakthrough seizures.