Alternative anticonvulsant drugs for dogs with seizure disorders - Veterinary Medicine
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Alternative anticonvulsant drugs for dogs with seizure disorders
People with seizure disorders have many drug options, but are there safe and effective alternatives to phenobarbital and bromide in dogs? These clinicians share their knowledge of the most promising new drugs.


VETERINARY MEDICINE


Orally administered levetiracetam approaches 100% bioavailability in dogs, with a serum half-life of three or four hours (UCB Pharma, Inc.: Unpublished data, 2004).27 Levetiracetam appears to exert an anticonvulsant effect that persists longer than its presence in the bloodstream would suggest.23 About 70% of oral levetiracetam is excreted unchanged in the urine; the remainder of the drug is hydrolyzed in the serum and other organs. There does not appear to be any hepatic metabolism of levetiracetam in people or dogs (UCB Pharma, Inc.: Unpublished data, 2004).22-24,27 The effective serum concentration is 5 to 45 g/ml in people.18 Since there is no clear relationship between serum drug concentration and efficacy for levetiracetam, and since the drug has an extremely high margin of safety, routine therapeutic drug monitoring is not typically recommended in people.17,23,25,26 Based on limited pharmacokinetic information in dogs, we recommend an initial dosage of 20 mg/kg given every eight hours (UCB Pharma, Inc.: Unpublished data, 2004).27 This dose can be increased by 20-mg/kg increments until efficacy is achieved, side effects become apparent, or the cost becomes prohibitive.

Long-term toxicity data for levetiracetam in dogs confirm that the drug is extremely safe. In one study, dogs were administered oral levetiracetam at dosages up to 1,200 mg/kg/day for one year.28 One of eight dogs receiving 300 mg/kg/day developed a stiff, unsteady gait. The remainder of side effects (salivation, vomiting) were limited to the dogs receiving 1,200 mg/kg/day. There were no treatment-related mortalities and no treatment-related histopathologic abnormalities (UCB Pharma, Inc.: Unpublished data, 2004). We have used levetiracetam in dogs as an add-on therapy with favorable results. In a recent report, using levetiracetam as an add-on drug in 15 epileptic dogs was associated with a significant reduction (54%) in seizure frequency, with no apparent side effects.28

Zonisamide

A sulfonamide-based anticonvulsant recently approved for use in people, zonisamide is effective in treating focal and generalized seizures with minimal side effects.29-33 Suspected anticonvulsant mechanisms of action include blocking T-type calcium and voltage-gated sodium channels in the brain, modulating dopaminergic metabolism in the central nervous system, scavenging free radical species, enhancing actions of GABA in the brain, and inhibiting carbonic anhydrase activity.17,18,29-31 Zonisamide is metabolized primarily by hepatic microsomal enzymes, and the half-life in dogs is about 15 hours.34 In people, the half-life of zonisamide is dramatically shorter (up to 50%) in patients concurrently receiving drugs that stimulate hepatic microsomal enzymes.33,35 A similar phenomenon may also occur in dogs, although this is not well-documented.

When zonisamide is used as an add-on therapy for dogs already receiving drugs requiring hepatic metabolism (e.g. phenobarbital), we recommend an initial oral dosage of 10 mg/kg given every 12 hours. This dosage has been shown to maintain canine serum zonisamide concentrations within the therapeutic range reported in people (10 to 40 g/ml) when used as an add-on therapy.18,36 For dogs not receiving hepatic microsomal enzyme-inducing drugs, we recommend 5 mg/kg given every 12 hours. Trough serum zonisamide concentrations should be checked about one week after you institute therapy. Zonisamide has a high margin of safety in dogs. In one study, minimal side effects occurred in beagles administered zonisamide dosages up to 75 mg/kg/day for one year.37

In a recent study, zonisamide decreased seizure frequency by at least 50% in seven of 12 dogs with refractory idiopathic epilepsy. In this responder group, the mean reduction in seizure frequency was 81.3%. In six of the seven responder dogs, phenobarbital was able to be reduced by an average of 92.2%. Mild side effects (e.g. transient sedation, ataxia, vomiting) occurred in six dogs (50%); none of the side effects were considered severe enough to discontinue zonisamide therapy.36

We have used zonisamide as a sole anticonvulsant drug in a number of dogs, primarily small-breed dogs whose owners wanted to avoid the side effects characteristic of phenobarbital and bromide. Our impression is that zonisamide is usually effective as a sole anticonvulsant therapy, with few to no apparent side effects.


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Source: VETERINARY MEDICINE,
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