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Comparing transdermal with oral phenobarbital administration in epileptic cats

Barnes-Heller HL et al.  “Prospective crossover clinical trial comparing transderma with oral phenobarbital administration in epileptic cats.” J Feline Med Surg, 2019: 21(12); 1181-1187. 

Phenobarbital is the most commonly prescribed antiepileptic drug for cats with epilepsy and other forms of non-metabolic seizures. Though effective and generally well tolerated, oral phenobarbital administration can be a significant challenge, resulting in stress for both the cat and owner, and occasionally owner injury. Transdermal drug administration has been shown to be better tolerated and easy to administer, and may represent a practical alternative to oral administration. Previous investigations of transdermal administration of drugs such as methimazole have demonstrated that owner compliance was improved, and effective disease management was achievable.

The objective of the present study was to compare serum phenobarbital concentrations as well as adverse effects and owner satisfaction during 14 weeks of transdermal versus oral phenobarbital administration to cats with epilepsy. The authors aimed to determine whether serum phenobarbital concentrations correlated with dosage by both routes of administration. The authors hypothesized that more owners would prefer transdermal administration over the oral route.

The study was designed as a prospective, fixed-order, crossover study, whereby client-owned cats with idiopathic epilepsy were administered oral phenobarbital for 14 weeks, then all cats were transitioned to transdermal phenobarbital for an additional 14 weeks. Serum phenobarbital concentrations were measured at weeks 2, 14, 16 and 28. Client satisfaction questionnaires and serum biochemistry panels were evaluated at 14 and 28 weeks.

Overall, 9 client-owned cats with presumptive or confirmed idiopathic epilepsy were included in the present study. Cats being treated with corticosteroids or other medications such as methimazole were excluded from the study, and cats presently receiving phenobarbital were eligible for inclusion. Phenobarbital was administered orally at a median dose of 3.8 mg/kg (2.0-5.4 mg/kg) every 12 hours for weeks 1 to 14. Afterward, phenobarbital was administered transdermally at a median starting dose of 18.8 mg/kg (17.6-24 mg/kg) every 12 hours for weeks 15 to 28.

Results indicated that phenobarbital concentrations were significantly associated with oral dosages at week 2, and few dose adjustments were needed. Transdermal dosages were poorly correlated with serum phenobarbital concentrations, and more frequent dose adjustments were required compared to oral administration. Moreover, there appeared to be greater variability among individual cats, whereby transdermal dosage adjustments were not as predictable as oral dosage adjustments in reaching target serum concentrations. One cat in the study even had undetectable serum phenobarbital concentrations after 2 weeks of transdermal phenobarbital administration at an accidental 1.3 x intended dose increase (24 mg/kg/day). This individual was returned back to oral administration, due to a marked increase in seizure activity.

Overall, 6/9 (67%) owners preferred transdermal to oral administration, even taking into account the need for more frequent bloodwork to measure serum drug concentrations and dose adjustments compared to the oral group. The remaining 3/9 owners preferred oral administration because of the requirement for fewer dose adjustments (n=2) and ease of administration for their cat (n=1).  The adverse events reported were infrequent (approximately 22% of cats during transdermal phase), mild and comparable for both groups. The most commonly reported adverse effects were ataxia, weakness and lethargy.

Several potential limitations of the present study exist, including its small sample size and non-randomized crossover patient distribution. Prior treatment with phenobarbital was permitted to increase the eligible pool of subjects, which may or may not affect results based on previous hepatic enzyme activation. However, the owners remark that enhanced biotransformation of phenobarbital secondary to hepatic enzyme activation has not been previously reported or found with chronic oral administration in cats, therefore this mechanism was considered unlikely to have influenced results. Moreover, a theoretical risk of dosage alterations exists due to the fact that transdermal formulations are only available through compounding pharmacies, which could potentially lead to variations in drug concentrations between batches.

Based on the study’s results, the authors concluded that serum phenobarbital concentrations were achievable with transdermal administration but required more dosage adjustments compared to the oral route, as serum concentrations did not reliably correlate with the transdermal dose. This implies that consistent and frequent monitoring is indicated, and owners should be warned of the likely need for more frequent dose adjustments before the beginning of treatment. Overall, client satisfaction was greater and fewer doses were missed with transdermal administration compared to the oral group. (HM)

See also:

Hazenfratz M, Taylor SM. “Recurrent Seizures in Cats: Treatment – Which Antiepileptic Drugs Are Recommended?” J Feline Med Surg. 2018 Sep;20(9):825-834.