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.


No published information documents the efficacy of clorazepate in dogs with seizure disorders. In our experience, clorazepate is a moderately effective alternative anticonvulsant drug. In dogs already receiving phenobarbital, maintaining the correct dosage of clorazepate can be troublesome. Another potential use for clorazepate is for short-term treatment in dogs experiencing cluster seizure episodes.


Felbamate is a dicarbamate anticonvulsant drug used for both focal (partial) and generalized seizures in experimental studies in animals and clinical trials in people.1,2,8,9 Felbamate's suspected mechanisms of action include blocking N-methyl-D-aspartate (NMDA)-mediated neuronal excitation, potentiating GABA-mediated neuronal inhibition, and inhibiting voltage-sensitive neuronal sodium and calcium channels.1,2,8-11 There is also evidence that felbamate offers some protection to neurons against hypoxia and ischemic damage.8,9 About 70% of oral felbamate in dogs is excreted in the urine unchanged; the remainder undergoes hepatic metabolism. The half-life of felbamate in adult dogs is about five to six hours, with a range of four to eight hours.1,2,8,11,12 Although felbamate is well-absorbed after oral administration in adult dogs, it has been shown that the bioavailability in puppies may be only 30% of that in adults. The half-life in puppies has also been demonstrated to be much shorter than in adult dogs (i.e. about 2.5 hours).13,14

In adult dogs, we recommend an initial felbamate dosage of 15 mg/kg given every eight hours. Felbamate has a wide margin of safety in dogs, with serious toxic effects usually not apparent when dogs are given less than 300 mg/kg/day.1,2,8,10,15 If the initial dose of felbamate is ineffective, we generally increase it in 15-mg/kg increments every two weeks until efficacy is achieved, unacceptable side effects become evident, or the drug becomes cost-prohibitive. The therapeutic range for serum felbamate concentrations in dogs is thought to be similar to that in people (20 to 100 g/ml).2,10 Serum felbamate assays are typically costly and are usually unnecessary because of the drug's low potential for toxicity.

Side effects are infrequent with felbamate use in dogs. A principal advantage of felbamate over standard anticonvulsant drugs is that it does not cause sedation. Because felbamate undergoes some hepatic metabolism, liver dysfunction is a potential side effect.1,2,8,10 In one study, four of 12 dogs receiving felbamate as an add-on therapy developed liver disease. However, all of these dogs were also receiving high doses of phenobarbital.16 In people, felbamate has been shown to increase serum phenobarbital concentrations in some patients receiving combination therapy.2,17 It is unclear whether felbamate, phenobarbital, or a combination of the two drugs is responsible for the reported hepatotoxicity in dogs. In people, serious hepatotoxicity is rarely encountered with felbamate use and almost always occurs in patients receiving other anticonvulsant drugs concurrently.2,9,18 If a dog already has a liver problem, felbamate should be avoided. In our experience, if a dog develops liver disease, the condition is typically reversible when felbamate is discontinued. However, we rarely encounter dogs with liver problems in which felbamate has been used as the sole therapy.

Aplastic anemia from bone marrow suppression has been reported in people receiving felbamate at a rate of 10 per 100,000 patients; this uncommon side effect is also usually encountered in patients receiving combination anticonvulsant drug therapy.2,18 This devastating side effect does not appear to occur in dogs receiving the drug. In one report, however, reversible bone marrow suppression was suspected in two dogs receiving felbamate; one dog developed mild thrombocytopenia, the other mild leukopenia.19 Both of these abnormalities resolved with felbamate discontinuation. One patient in this report developed bilateral keratoconjunctivitis sicca; it is unknown if this was related to felbamate use.19 Generalized tremor activity in small-breed dogs receiving high doses of felbamate has also been reported as a rare side effect.10


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