New anticonvulsant drugs show promise in dogs, cats - DVM
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New anticonvulsant drugs show promise in dogs, cats


DVM360 MAGAZINE


As sole drug therapy

There are a number of reports in human medical literature supporting the use of some of these new anticonvulsant drugs as sole therapy. Because they have minimal side effects, they may offer an advantage over more standard drugs used in dogs. And, as the price decreases for generic versions, there will be more opportunities to use these newer agents as standard therapy, especially in small-breed dogs.

Anecdotally, felbamate can be used as a sole anticonvulsant drug. In most cases, it is used to avoid the side effects of phenobarbital or potassium bromide. Such cases include the management of disorders in which the underlying disease and its treatment may result in worsening clinical signs with the addition of standard anticonvulsant drugs (e.g., obtunded brain tumor and GME dogs receiving prednisone).

In addition, dogs with suspected idiopathic epilepsy have been treated with zonisamide as a sole anticonvulsant drug. It appears to perform well as a sole anticonvulsant drug for canine idiopathic epilepsy.

New feline anticonvulsant drugs

Until recently, the only anticonvulsant drug known to be safe and effective for feline use was phenobarbital. The use of gabapentin for seizures in cats remains anecdotal, with unproven efficacy. Due to the length of time that such anecdotal use has been discussed in the veterinary literature (with no reports of serious side effects), and the known safety of the drug in other species (i.e., humans, dogs), it is likely to be a safe drug in cats.

Levitiracetam has been used as an add-on (to phenobarbital) oral anticonvulsant drug in a few cats with suspected refractory idiopathic epilepsy. It was found to be an effective add-on anticonvulsant, and serum levitiracetam levels are maintained within the therapeutic range reported for people (5-45 ug/mL) using a 20 mg/kg every 8 hours dosing regimen. Side effects are limited to transient (one to two weeks) lethargy and inappetence; these resolved without adjusting drug dosage.

Levitiracetam can be used as second-line anticonvulsant drug choice for cats poorly controlled with phenobarbital alone.

Emergency seizure management

The current standard of care for treating dogs with cluster seizures or status epilepticus is to administer highly sedative drugs to halt seizure activity. As diazepam often fails in these animals, the induction of a light plane of anesthesia using barbiturates or propofol often is required.

In addition to posing some risk, it may be difficult or impossible to add additional maintenance anticonvulsant drugs to the treatment protocol during this time period.

Both intravenous levitiracetam and intra-rectal zonisamide hold potential as useful emergency anticonvulsant treatment options for dogs.

A commercial form of intravenous levetiracetam was recently introduced. A single-dose pharmacokinetic study with this drug formulation in normal dogs, using an intravenous bolus dose of 60 mg/kg over two minutes, showed no apparent side effects and all dogs reached and maintained plasma levitiracetam concentrations within or exceeding the therapeutic range reported for humans for the entire eight-hour evaluation period.

A prospective clinical evaluation of intravenous levitiracetam use in dogs with cluster seizures and status epilepticus is under way.

Newer versions

Recent insights into the mechanisms of action of two of the new anticonvulsant drugs (gabapentin and levitiracetam) have generated developments of the next generation drugs with increased anticonvulsant potency.

The successor to gabapentin is pregabalin, which has greater affinity for the voltage-gated calcium channels than its predecessor. There are two successors to levitiracetam — brivaracetam and seletracetam — both of which have greater affinity for SV2A than levitiracetam.

Because of the problems of hepatotoxicity and blood dyscrasias occasionally associated with felbamate use in people, a new derivative of the drug, fluorofelbamate, has been developed. The substitution of fluorine for hydrogen in a critical place in the molecule is believed to prevent the formation of the toxic metabolite responsible for the reported side effects.

All of these drugs appear to have greater anticonvulsant activity in experimental rodent models than their predecessors. Pregabalin also has shown greater anticonvulsant efficacy than gabapentin in people. Brivaracetam, seletracetam and fluorofelbamate are in clinical trials. Pregabalin is commercially available, but the appropriate dose regimen for oral pregabalin in dogs is still unknown.

Dr. Hoskins is owner of Docu-Tech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail:


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Source: DVM360 MAGAZINE,
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