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


Pregabalin

Pregabalin is a newer-generation drug in the same class as gabapentin. Limited information exists on its use in dogs as a treatment for epilepsy. Based on pharmacokinetic data in normal dogs, a dose of 2 to 4 mg/kg orally every eight hours has been recommended and was administered to six dogs with idiopathic epilepsy refractory to treatment with phenobarbital, potassium bromide, or both drugs.11 One dog was considered a drug failure, and four of the five remaining dogs had a mean seizure reduction of 59.3%. Five dogs exhibited side effects (sedation and ataxia) attributed to pregabalin.

Zonisamide

Zonisamide is a sulfonamide-derived antiepileptic drug introduced in the United States in 2000. Its half-life in dogs is 15 to 20 hours, which is relatively long when compared with the other new antiepileptic drugs, and it requires only twice-daily administration. Most of the drug is excreted unchanged by the kidneys, although some hepatic metabolism occurs. The dosage in dogs is 5 to 10 mg/kg given orally every 12 hours. The high end of the dose range is recommended when the drug is used in combination with phenobarbital since phenobarbital appears to facilitate zonisamide clearance.12 For this reason, it may also be helpful to measure serum zonisamide concentrations in dogs being treated concurrently with phenobarbital. A therapeutic range of 10 to 40 μg/ml has been suggested,13 which is similar to the therapeutic range in people. Zonisamide is a known teratogen in dogs, so its use should be avoided in pregnant animals.

Two recent reports on zonisamide as add-on therapy in dogs with refractory epilepsy demonstrated a favorable response in seven of 12 and nine of 11 dogs.13,14 Reported side effects included sedation, ataxia, and loss of appetite. A generic form of zonisamide is available, which has reduced the cost considerably since its introduction.

Levetiracetam

Levetiracetam (Keppra—UCB Pharma) is one of the more recently approved human antiepileptic drugs. Its unique mechanism of action is a potential advantage when the drug is used in combination with other antiepileptic drugs. Levetiracetam has minimal hepatic metabolism in dogs, with more than 80% of the drug excreted in the urine. The half-life in dogs is three to four hours, which necessitates frequent administration. The recommended oral dose is 20 mg/kg every eight hours.

A recent study evaluated levetiracetam as an add-on medication in dogs with idiopathic epilepsy that was refractory to phenobarbital and potassium bromide.15 Nine of 14 dogs responded, and the only side effect was sedation, which was observed in one dog. The main factor limiting the use of levetiracetam in dogs has been its expense, although a generic form of this drug has also recently become available.

Levetiracetam is also available in a parenteral formulation. One pharmacokinetic study has evaluated the disposition of the drug in six dogs after intravenous and intramuscular administration.16 A dose of 20 mg/kg results in desirable serum concentrations in a short period; with intramuscular administration, peak concentrations are reached in 40 minutes. Thus, this drug may prove useful in treating cluster seizures and status epilepticus in dogs, with the option of administering the drug intramuscularly if venous access cannot be obtained.


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Source: VETERINARY MEDICINE,
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