Open‐label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures

Abstract

Background Treatment options for at‐home management of cluster seizures (CS) and status epilepticus (SE) are limited. The pharmacokinetics of levetiracetam (LEV) after rectal administration in both healthy and epileptic dogs has been investigated recently. Hypothesis/Objectives To investigate the clinical efficacy of rectally administered LEV in preventing additional seizures in dogs presented for CS and SE. We hypothesized that rectal administration of LEV in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone. Animals Fifty‐seven client‐owned dogs with CS or SE. Methods Prospective open‐label clinical trial. Patients included in the study were assigned to receive either a standard treatment protocol comprising IV/rectal diazepam and IV phenobarbital q8h (control group) or a standard treatment protocol in association with a single dose of 40 mg/kg LEV rectally (rectal LEV group). Dogs that experienced no additional seizures were defined as responders, whereas those that showed additional seizure activity were classified as nonresponders. Results Twenty‐one dogs were assigned to the rectal LEV group, and 36 to control group. Given the small number of cases of SE, statistical analysis was performed only on patients with CS. The response rate was 94% in the rectal LEV group and 48% in the control group ( P < .001). Conclusions and Clinical Importance Rectally administered LEV combined with a standard treatment protocol provided good control of seizure activity in patients with CS. The validity of these results should be confirmed in a double‐blinded, placebo‐controlled clinical trial.

Comparison of Certain Intrarectal versus Intramuscular Pharmacodynamic Effects of Ketamine, Dexmedetomidine and Midazolam in Cats

“…Different routes of administration could elicit different pharmacokinetic and pharmacodynamic responses of the same drug mixture. A decreased uptake of drugs is already known for benzodiazepine in dogs for IR; as suggested by [ 11 , 17 ], similar clinical effects occur with a range dose of 0.5–2 mg kg −1 in IR and 0.2–0.3 mg kg −1 in IV administration of diazepam. This consideration would seem valid for midazolam: IV and IR at the same posology present lower bioavailability in the second case [ 18 ].…”

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

“…After the exclusion of duplicates, 87 (SE) and 28 (CS) studies remained and entered stage 2 screening. Of these, 38 clinical studies 2,3,37‐40,43‐74 (SE; dogs, n = 36; cats, n = 5) and 12 clinical studies 37,40,48,49,57,64,75‐80 (CS; dogs, n = 12; cats, n = 0) as well as 37 pharmacokinetic studies 49,57,65,81‐114 (dogs, n = 33; cats, n = 4) fulfilled stage 2 criteria and were selected for review. Some clinical studies included a mixed populations of dogs and cats.…”

“…Pulse treatment has been recommended instead of long‐term continuous treatment, because it might prevent the development of tolerance associated with the drug's chronic use 77 . In the out‐of‐hospital setting, PO levetiracetam can be used as a first‐choice; R administration also can be used in dogs, especially when PO administration is not possible 49,76,77,101 . In dogs that are receiving chronic phenobarbital treatment, a higher dose of levetiracetam may be needed 77 .…”

The standards of reporting trials in pets (PetSORT): Explanation and elaboration

“…"Given the small number of patients admitted with SE (status epilepticus) in both groups, statistical analysis was performed taking into consideration only patients affected by CS (cluster seizures)." (119) "The possible confounding effects of the intraoperative administration of hydromorphone on recovery were evaluated. Twelve dogs in group P and 10 dogs in group KD did not receive hydromorphone at any time during the anesthetic period.…”