Levetiracetam in the management of feline audiogenic reflex seizures: a randomised, controlled, open-label study

Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as “epileptic” and “nonepileptic” based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage‐gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.

Section: Treatmentsupporting

confidence: 65%

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

Lowrie¹,

Garosi

2017

“…The C max was higher than the maximal reference interval for humans (45 μg/mL) in all cats, but adverse effects were minimal and neurologic examination findings remained normal in all cats, indicating tolerance of the increased C max . Reported adverse effects in cats after PO levetiracetam administration include lethargy, anorexia, ataxia, polydipsia, and hypersalivation . After multi‐dose administration of IRL, a reported 18% of cats developed adverse effects, but all signs resolved within a 2‐week period without dose adjustment .…”

Section: Discussionmentioning

confidence: 99%

“…Levetiracetam is an AED approved for use in humans. Its novel mechanism of action coupled with minimal reported adverse effects makes it an appealing drug for seizure control in cats . Pharmacokinetics of intermediate‐release levetiracetam (IRL)‐administered PO in cats support a 20–25 mg/kg dosage, but the short elimination half‐life of 2.95 ± 0.95 hours necessitates a q8h dosing regimen, decreasing owner compliance .…”

mentioning

confidence: 99%

Pharmacokinetics of Single Oral Dose Extended‐Release Levetiracetam in Healthy Cats

Barnard

Heller

Boothe

2017

BackgroundRepeated PO dosing of anti‐epileptic drugs may contribute to poor compliance in treated cats. Intermediate‐release levetiracetam has been used safely in cats, but must be given q8h to maintain serum concentrations in the therapeutic interval for humans (5–45 μg/mL). Approved extended‐release levetiracetam (XRL) for human use may require less frequent dosing, but the large dosing unit has limited its use in cats.HypothesesIn healthy cats, serum levetiracetam concentration will remain above 5 μg/mL for at least 24 hours after administration of a single dose of XRL PO and will be well tolerated.Animals7 healthy cats.MethodsExtended‐release levetiracetam (500 mg) was administered PO. Blood was collected and neurologic examination findings recorded at scheduled times over 30 hours. Serum levetiracetam concentration was quantitated by an immunoassay validated in cats. Data were subjected to noncompartmental analysis. Descriptive statistics were reported.ResultsThe median dosage of 86.2 mg/kg, (range, 80–94.3) achieved a mean maximum concentration (C max) of 89.8 ± 25.8 μg/mL at 4.9 ±1.57 hours. Serum levetiracetam was >5 μg/mL in all cats by 90 minutes. Mean concentrations were 43.7 ± 18.4 and 4.9 ± 3.4 μg/mL at 12 and 24 hours, respectively. The half‐life was 4.1 ± 1.0 hours. The drug was well tolerated.Conclusions and Clinical ImportanceA single 500 mg PO dose of XRL safely maintained serum levetiracetam concentration ≥5 μg/mL in healthy cats for at least 21 hours. Clinical efficacy studies in epileptic cats receiving XRL are indicated; however, monitoring should be implemented for individual cats.

“…Epileptic seizures are the most common reason cats are presented to veterinary neurologists and often antiepileptic drugs (AED) are recommended for long‐term seizure control regardless of the etiologic diagnosis. Although many cats have favorable seizure control with PO administration of phenobarbital and intermediate‐release levetiracetam (IRL), administration 2–3 times daily long‐term may be difficult for owners, leading to poor compliance.…”

Section: Introductionmentioning

confidence: 99%

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats

Heller

Granick

Hesteren

et al. 2018

BackgroundMultiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats.ObjectiveEvaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats.AnimalsNine healthy privately owned cats, body weight ≥ 5 kgMethodsExtended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats.ResultsMedian dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3‐14.1), 82.6 (7.8‐125.3), 92.3 (13.3‐97.3), and 72 (22.8‐96.4) μg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (C max) by 8 hours (n = 2). Median time of maximal concentration (T max) for the remaining 5 cats 5.2 (range 4‐6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment.Conclusions and Clinical ImportanceMean trough serum levetiracetam concentrations were ≥5 μg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate‐release levetiracetam for epileptic cats.