Newer options for medically managing refractory canine epilepsy - Veterinary Medicine
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Newer options for medically managing refractory canine epilepsy
Where do you turn when an epileptic dog responds poorly to phenobarbital or potassium bromide? One of several novel therapies borrowed from epilepsy treatment in people may help.


VETERINARY MEDICINE


ALTERNATIVE SEIZURE MEDICATIONS


TABLE 1: Characteristics of the New Antiepileptic Drugs Used to Treat Canine Epilepsy
Factors to consider when choosing an add-on medication include 1) mechanism of action, with preference given to drugs with a differing mechanism, 2) side effects, 3) the potential for drug interactions among antiepileptic drugs, 4) the required frequency of administration, which in turn may influence compliance, and 5) the cost. The important features of the new antiepileptic drugs approved for use in people being used extralabel in dogs are summarized in Table 1 and are discussed in more detail below.

Felbamate

Felbamate was the first of the newer antiepileptic drugs to be approved in the United States for epilepsy in people. Side effects of aplastic anemia and hepatotoxicosis have since been reported in people, so its use has declined. The half-life of felbamate in dogs is five to eight hours, and the recommended oral dosage is 15 to 60 mg/kg every eight hours. Initiate treatment at the low end of the dosage range, and increase it as needed to control seizures. Felbamate serum concentrations are not routinely monitored, as is the case for many of the newer antiepileptic drugs. Rather, the drug is used to effect, and dosage adjustments are based on seizure frequency and side effects. Although most of the drug is excreted in the urine in dogs, some hepatic metabolism occurs, increasing the potential for drug interactions when phenobarbital and felbamate are administered concurrently.

One study has evaluated the use of felbamate as a sole antiepileptic drug in six dogs with partial onset seizures.5 Dosages ranged from 60 to 220 mg/kg/day, and all dogs showed reduced seizure frequency. Two dogs developed blood dyscrasias, characterized by thrombocytopenia, lymphopenia, and leukopenia, which resolved after the drug was discontinued. One dog developed keratoconjunctivitis sicca, although it was not determined that this problem was drug-related.

The use of felbamate as an add-on therapy has been reported in 16 dogs refractory to phenobarbital and potassium bromide.6 Twelve dogs had improved seizure control, but four of these dogs developed signs of liver dysfunction. Other side effects anecdotally reported in dogs receiving felbamate in combination with phenobarbital include sedation, nausea, and vomiting.7 It is recommended that complete blood counts and liver enzyme activities be measured every two or three months during treatment to assess for adverse effects. However, felbamate is used infrequently in veterinary patients because of the potential for side effects and drug interactions and because of the expense.

Gabapentin

Gabapentin was approved in the United States for use in people as an antiepileptic drug shortly after felbamate. Since its introduction, gabapentin has also been approved to treat neuropathic pain. In people, gabapentin is eliminated entirely by the kidneys, but in dogs it undergoes partial hepatic metabolism. The elimination half-life in dogs is two to four hours, requiring frequent drug administration to achieve steady-state concentrations. The recommended oral dosage is 10 to 20 mg/kg every six to eight hours.

Two studies have examined the use of gabapentin in refractory canine epilepsy. The first study involved 11 dogs administered gabapentin (10 mg/kg t.i.d.) in addition to phenobarbital and potassium bromide.8 A positive response to gabapentin, defined as ≥ 50% reduction in seizure frequency, was reported in six of the 11 dogs. The second study evaluated 17 dogs with refractory seizures that were administered gabapentin at a dose of 35 to 50 mg/kg/day divided twice or three times daily, also in conjunction with phenobarbital and potassium bromide (16 dogs) or phenobarbital alone (1 dog).9 This study found no significant decrease in the number of seizures over the study period for the entire population of dogs. However, seizures resolved in three dogs while they were receiving the medication. The side effects reported in both studies were sedation and ataxia.

The availability of generic gabapentin has made it affordable relative to other antiepileptic drugs used in veterinary patients. A liquid formulation (50 mg/ml concentration) of gabapentin exists, which facilitates the administration of lower doses to smaller patients. However, the liquid product contains 300 mg xylitol/ml, so it has the potential of causing adverse effects associated with the ingestion of this sugar alcohol.10 Consequently, I recommend that the tablet or capsule form of gabapentin be used preferentially in dogs.


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Source: VETERINARY MEDICINE,
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