July 25, 2018

Managing Feline Epilepsy With Extended-release Levetiracetam

A new study evaluated the serum concentrations and adverse effects of once-daily dosing of extended-release levetiracetam in healthy cats.
By Rebecca A. Packer, MS, DVM, DACVIM (Neurology/Neurosurgery)
Feline EpilepsyAdministering oral medications to cats can be difficult for owners, and stressful for both owners and patients. In the case of patients with epilepsy, this difficulty and stress could lead to poor compliance and uncontrolled disease.

The pharmacokinetics of levetiracetam in cats have been previously reported. Due to the half-life of regular-release formulations, 3-times-daily dosing was recommended. Investigators from the University of Wisconsin School of Veterinary Medicine recently evaluated the concentrations and adverse effects of once-daily dosing of extended-release levetiracetam. The results were published in the Journal of Veterinary Internal Medicine.

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Study Design
Nine healthy owned cats were enrolled in the study. All cats received 500 mg (median, 94.3 mg/kg; range, 75.7-98.0 mg/kg) of oral extended-release levetiracetam once daily for 11 days. The medication was administered in the morning. On day 11, a trough blood sample was collected from each cat prior to medication administration and 4, 6, and 8 hours after dosing for pharmacokinetic analysis. Serum biochemical profiles were performed on days 0 and 11. Throughout the study period, owners kept daily logs describing any adverse events, appetite, as well as timing of meals and medications.

Results and Discussion
Whole tablets were administered successfully to all cats to preserve the extended-release properties of the medication. Peak concentration (Cmax) could only be calculated in 5 of 9 cats. Two cats failed to reach Cmax by the 8-hour blood sampling, so data were not available for peak concentration; and 2 cats were uncooperative and samples could not be obtained. Due to these missing samples, samples from 8 of 9 cats were available for analysis at times 4, 6, and 8 hours.

Based on the available data, mean Cmax was 102.5 mg/mL (range, 92.7-125.3 mg/mL). Although sample sizes were very small, cats that ate at the time of medication administration had higher Cmax (n = 2; mean, 114.45 mg/mL; range, 103.6-125.3 mg/mL) compared with cats that did not eat (n = 3; mean, 94.6 mg/mL; range unavailable). Whether this is consistent among a larger population of cats is unknown and requires additional study. Mean trough concentration was 8.0 mg/mL (range, 2.3-14.1 mg/mL) based on data from 9 cats.

Adverse effects were transient or sporadic, and mild. One cat exhibited ataxia on day 1 only. One cat exhibited sedation on day 2 only. One cat vomited or regurgitated on days 3 and 7 only. No dose adjustments were necessary. In all cats, no significant changes in serum biochemical profiles were identified between days 0 and 11.

Clinical Impact
Once-daily dosing of extended-release levetiracetam (500 mg, administered orally, for cats > 5 kg) in healthy cats was well tolerated and did not result in drug accumulation based on serum concentrations. Although not discussed in this article, cats with renal insufficiency may be at greater risk of drug accumulation, and monitoring serial trough concentrations in such patients may be indicated. Peak concentrations were higher, and trough concentrations were lower, than most published human therapeutic ranges; however, therapeutic ranges for cats remain unknown. As with any antiepileptic drug, monitoring for signs of long-term toxicity and breakthrough seizures remain important components of thorough patient management.

 
Dr. Packer is an associate professor of neurology/neurosurgery at Colorado State University College of Veterinary Medicine and Biomedical Sciences in Fort Collins, and is board certified in neurology by the American College of Veterinary Internal Medicine. She is active in clinical and didactic training of veterinary students and residents and has developed a comparative neuro-oncology research program at Colorado State University.

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