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Keppra and Zonisamide – New Treatments for Seizures in Dogs and Cats

Seizures Dogs

Dr. Magnusson’s dog Sophie has had 3 seizures in 14 years.

This article is written in part after consultation with our friends, veterinary internal medicine specialist Kristi Graham, DVM, DACVIM and veterinary neurologist Johnny ( Randy ) Cross, DVM, ACVIM / neurology.


Seizures in dogs are scary to watch. My dog Sophie, who is 14, has had three seizures total in her little lifetime. Even as a veterinarian, I watched helplessly knowing there was nothing I could do to help her until the seizure was over. I never have started Sophie on seizure drugs because of how rare her seizures are. Veterinarians usually only treat seizures if they happen more often than once a month, or if they happen in clusters (several seizures in a day).

There is no drug available that 100% controls all seizures in dogs. Even more frustrating, doctors and veterinarians mostly have no idea why antiepileptic drugs control seizures, we just know that they work. Sometimes.

Phenobarbital – Still most veterinarians’ first choice for seizure therapy, phenobarb can cause sedation for up to the first 3-4 weeks of therapy, and there is a risk of liver damage with ongoing use. Most dogs starting phenobarbital will drink more, pee more, and feel hungrier while on phenobarb, so it’s important to make sure you don’t overfeed and cause obesity in these dogs. Phenobarbital also lowers blood thyroid hormone levels, which makes dogs with normally functioning thyroids look as though they are hypothyroid. Since hypothyroidism is listed as a potential cause of neurologic diseases like seizures, alterations in blood thyroid levels might cause a veterinarian to start a dog on thyroid meds when they don’t need them (which isn’t the worst thing in the world, in most cases, but still).

On the other hand, thousands of dogs with “idiopathic epilepsy” (seizures of unknown cause) have found immense relief from recurring seizures for decades, through the use of phenobarbital, and we have a ton of experience with it. Blood tests can be done ongoing to measure blood levels of the drug and ensure you’re giving the proper dose. Best of all, even with recent price increases, phenobarbital is still the least expensive seizure drug available for dogs. Phenobarbital is usually dosed initially at 2-2.5mg/kg every 12 hours. A 60 pound dog would therefore start on what we call “one grain” of phenobarbital (65mg) twice a day. As of this writing, one month of phenobarbital for a 60lb dog would cost $12/mo. Phenobarbital is a closely-regulated FDA schedule IV controlled substance.

Potassium bromide ( KBr ) – When phenobarbital alone is not enough to control a dog’s seizures, most veterinarians will then add on potassium bromide to the protocol. Many owners report increased sedation with this additional drug. Because potassium bromide only comes in 500mg tablets, compounding pharmacies are often used to create liquids or tablets of the smaller dosages required to treat pets. A 60 pound dog started on 20-30mg/kg of potassium bromide would cost between $35-45/mo.

Keppra ( levetiracetam ) – Studies in dogs with this drug, approved by the FDA for human use in 1999, are ongoing. Some veterinarians may add Keppra to the phenobarbital protocol, others may try Keppra alone as sole therapy for seizures. In dogs, side effects may include drowsiness, changes in behavior and gastrointestinal symptoms such as vomiting or diarrhea, but these are very rare. In cats, a decrease in appetite can occur. Despite the previous list, most veterinarians consider keppra to be pretty much free of side effects (certainly far fewer than with phenobarb). The dose usually used is 20 mg/kg orally every eight hours. The “every eight hours” dosing is the major downside of Keppra use in pets, as many pet owners are unable to maintain that dosing schedule reliably because of their own busy schedules. Keppra comes as immediate release 250 or 500mg tablets (to be given every 8 hours) or 500mg extended release tablets (to be given every 12 hours).

NOTE: It is EXTREMELY IMPORTANT that you price shop for Keppra. FOR EXAMPLE, 60 tablets of extended-release 500mg levetiracetam costs at three pharmacies:
1) CVS – $ 240
2) Walgreens – $ 245 cash, or $106 with a $20/year Walgreens Savings Club Card
3) Costco – $ 36.76 (!!)

Zonisamide – As with most anticonvulsant drugs, zonisamide can cause drowsiness, incoordination and a depressed appetite in dogs, but side effects are far fewer and milder than with phenobarbital. Dogs concurrently receiving phenobarbital therapy tend to require a higher zonisamide dose (10 mg/kg, q 12 hours) than dogs not receiving phenobarbital (5 mg/kg, q 12 hours). The twice daily dosing schedule for zonisamide is an advantage over the other new anti-epileptic drugs for many dog owners. Because zonisamide is a sulfa-based drug, we may expect to see rare toxicities including red and white cell changes, keratoconjunctivitis sicca, immune reactions, or idiosyncratic liver reactions.

NOTE: It is EXTREMELY IMPORTANT that you price shop for zonisamide. FOR EXAMPLE, 60 tablets (one month for a 30lb dog) of 100mg zonisamide costs at three pharmacies:
1) CVS – $ 226
2) Walgreens – $ 111 cash, or $54.99 with a $20/year Walgreens Savings Club Card
3) Costco – $ 14.88 (!!)

BOTTOM LINE: Dr. Cross, veterinary neurology specialist prefers to start all seizuring dogs on zonisamide because it is a twice daily drug, and can be obtained from Costco for $15-30/mo depending on the size of the dog. Dr. Graham, veterinary internal medicine specialist prefers to start seizuring dogs on Keppra because it is available as an extended release drug that can be given twice daily, and can be purchased for about the same $30-40/mo depending on the size of the dog. With smaller dogs, unfortunately, compounding pharmacies may still be required, which may dramatically increase the cost of these drugs. Both veterinarians agree that phenobarbital is still a fine first-line drug, very effective in controlling seizures, inexpensive and readily available, and great in many cases, as long as the potential side effects and toxicities are known, monitored, and managed. Their biggest concern with Keppra and zonisamide is that because these drugs started out so expensive, they have not been used very much in veterinary medicine, and side effects and toxicities may start to show up that we were not expecting.

Please also read our other seizure post – Managing Canine Epilepsy – An Owner’s Perspective

  • Lady’s mom

    Dr. Magnusson,

    Thank you for the information about Keppra and Zonisamide – New Treatments for Seizures in Dogs and Cats . My 14 year-old German Pointer mix, just has started having grand mal seizures, the first day, second day, and third day. No seizure on the forth day. The Vet gave her phenobarbitol yesterday (the forth day). At the weight of 60 lbs, I cannot carry her home, upstairs, to go potty. Keppra will allow me help my dog! Thank you!!! I just wished you were closer to Los Angeles; you’d be my dog’s DVM!

  • Cindy Mares

    My dog was on pheno for 5 days and now she has such severe hind leg weakness that she can’t walk. Yesterday we switched to keppra xr, will the pheno damage be permanent?

  • Cindy Mares

    My dog was on pheno for 5 days and now she has such severe hind leg weakness that she can’t walk. Yesterday we switched to keppra xr, will the pheno damage be permanent?

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