Levetiracetam (Keppra). The “Cluster Buster”

The management of chronic recurrent seizures in companion animals can often present a medical challenge to veterinarians and an economic and emotional obstacle for loving owners. With the availability of new anticonvulsants, greater latitude exists for anticonvulsant choice and success in the chronic management of companion animal seizures. With that said, the body of knowledge regarding the safety, efficacy and drug interactions with many of these newer agents remains in its infancy. Even less is known regarding their efficacy during cluster seizure events.

The use of “newer generation” anticonvulsants has allowed for greater control of companion animal recurrent seizures. As with all “off label” medications, unapproved for use in animals by the FDA, use should be based upon individual case selection and with the owner’s fully aware of the potential side effects and long-term uncertainty regarding safety. While it appears that these newer generation anticonvulsants are safe as chronic oral anticonvulsants, their use is often limited by their cost ($200-300 per month for a 40 kg dog). Of greater economic importance to owners of refractory cluster seizure patients, is the cost of emergency parenteral anti-epileptic treatment. Maintaining the care of these patients at home could make the difference in an owner’s decision to euthanize their pet due to recurring emotional and economic expense.

Levetiracetam is a pyrrolidone-derivative anticonvulsant approved by the FDA for use in partial seizures in humans. The anticonvulsant mechanism of action is not well understood. Levetiracetam may act by preventing hypersynchronization of epileptiform burst firing and propagation of seizure activity. These actions act to raise the seizure threshold, suppress paroxysmal depolarization shifts and the spread from the seizure focus.

Levetiracetam appears to be safe and effective in the treatment of companion animal seizures. Absorption following oral administration is felt to be rapid and complete. Elimination half-life is 4-5 hours in the dog. Plasma protein binding is limited at less than 10%. Levetiracetam undergoes minimal hepatic metabolism. Levetiracetam is excreted 65-75% unchanged in the urine through glomerular filtration and active tubular secretion. Clearance can be significantly reduced in patients with impaired renal function. Levetiracetam is relatively safe. Dogs given 1200 mg/kg/day developed salivation and vomition.

The management of recurrent cluster seizure patients remains a medical and economic challenge in Veterinary Medicine. Despite aggressive anticonvulsant therapy, cluster seizures can remain the pattern of the seizure patient. Failure to stop clustering events results in a costly, emotional and time-consuming visit to a local emergency facility. This only adds to the stress of owning and loving an epileptic pet.

The use of per-rectal Diazepam therapy (1 mg/kg if not receiving Phenobarbital therapy, and 2 mg/kg if receiving Phenobarbital therapy) or Clonazepam (0.2-0.5 mg/kg q8h) has been used with variable success in cessating continued cluster seizure activity within the home setting. Intranasal Midazolam(INMDZ) gel at 1 mg/kg appears to offer greater seizure control than per-rectal Diazepam. The mode of administration is also easier.

Keppra (Levetiracetam) is an effective as an oral, “pulse anti-epileptic” to control further seizures after the initial administration of INMDZ. Based upon the pharmacokinetics of Levetiracetam, therapeutic plasma concentrations are obtained within 1-3 hours following oral administration. Levetiracetam should be administered as soon as the pet can swallow, following the first noted seizure, and continued every 8h for a 24-hour seizure free period. A dosage of 20 mg/kg q8h is recommended.

In the short time we have begun utilizing this protocol in refractory, cluster seizure patients, we have seen a reduction in the number, frequency, and severity of seizures. We have also noted that these patients recover quicker following the cluster episode. The greatest benefit has been a reduction in the visits to an emergency facility for the owners. This economic benefit saves companion animal lives.

“The leading cause of death in recurrent seizure patients remains euthanasia.”