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Use of extended release levetiracetam for seizures in cats

Barnes Heller H, Granick M, Van Hesteren M, Boothe DM. Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats. J Vet Intern Med.2018 Apr 19. doi: 10.1111/jvim.15129.

Seizures are one of the more common neurologic conditions in cats, and are recognized and treated with increased frequency. Whether due to structural disease, epilepsy, or other conditions, anti-epileptic drugs (AEDs) form the backbone of disease management. While a wide variety of drugs are present on the market, many of them have limited utility in cats either due to their intolerable side effects (such as potassium bromide), their short half-lives (such as phenytoin), lack of efficacy as a sole agent (gabapentin, pregabalin), or are not widely available in many countries (zonesamide, imeptoin). As such, phenobarbital has remained the mainstay of seizure control in many cats, with levetiracetam a commonly used alternative. Both of these drugs require 2-3 doses to be given per day, which may be untenable for many cat owners.

Levetiracetam has a proven record of efficacy in dogs and cats, and may be preferred to phenobarbital in some conditions (such as audiogenic reflex seizures). It also has a minimal adverse effects profile and requires less careful monitoring than phenobarbital. The traditional drug has a very short half-life and requires dosing at an 8h interval. An extended release version of levetiracetam is commercially available, and preliminary kinetic studies have suggested once-daily dosing to be appropriate in cats. However, the smallest tablets commercially available are 500mg.

The purpose of this study was to determine the peak and trough levetiracetam concentrations in the blood of cats after 10 days of dosing, and to monitor for any adverse biochemical or clinical effects of dosing. The study was designed as a prospective clinical trial. 9 clinically and biochemically normal cats were enrolled into the study. Cats enrolled had no history of neurologic or other medical issues, weighed at least 5kg, and were on no medications other than flea/heartworm control. Baseline biochemistry was analyzed prior to study enrollment

Cats were administered one 500mg tablet by mouth once daily in the morning for 10 days. The median dosage per cat was 94.3mg/kg PO. During this period, owners kept a log of appetite, behaviours, and adverse events.  On day 11, blood was collected prior to the dose of levetiracetam (time 0) and then at 4, 6, and 8h after administration. Biochemical analysis was performed at the time 0 sample, and serum levetiracetam levels at all time points.

All cats were successfully administered the medication. No change to physical or neurologic exam were seen in any cat on day 11. No biochemical changes were noted. One cat experienced mild ataxia for one day, which resolved with no change in medication. One cat experienced sedation, which similarly resolved. A final cat experienced two episodes of vomiting. These adverse events were considered mild and self-limiting.

Serum levels greater than 5ug/mL of levetiracetam are considered to provide good seizure control in humans. The median trough concentration seen in this study was 8ug/mL. Serum levels at 4, 6, and 8 hours post dosing were 82.6, 92.3, and 7umg/mL respectively. Mean time to maximal serum concentration was 5.2h.

Some drawbacks to this study exist. These include the lack of a verified reference range for serum levetiracetam levels in cats, as well as the restriction of the study to cats weighing more than 5kg. The study was also not designed as a toxicity study, and so the possibility of adverse effects associated with the high serum levels cannot be ruled out. Due to the short half-life of levetiracetam in the blood, it is unlikely that longer courses of dosing would alter serum levels, however it is possible that a more prolonged trial may reveal other side effects of this drug. Finally, this study was in healthy cats, and so while measurement of serum levels was performed, this may not correlate with actual seizure control.

Despite these drawbacks, this study successfully demonstrated that extended release levetiracetam at 500mg/5kg cat may be a safe and effective method of seizure control in cats. If further studies can demonstrate long-term safety and clinical efficacy of this formulation, it shows potential to be a very useful method of seizure control in cats. (MRK)

See also:

Lowrie M, Thomson S, Bessant C, Sparkes A, Harvey RJ, Garosi L. Levetiracetam in the management of feline audiogenic reflex seizures: a randomised, controlled, open‐label study. J Feline Med Surg. 2017;19:200–206.