Transdermal Phenobarbital: Should we do it?
Okay, first I need to provide a disclaimer. My research projects was published a few weeks ago so I'm writing from a place of passion...and quoting myself! (Barnes Heller HL, et al. J Feline Med Surg 2019:21(12): 1181-1187.)
What makes a good transdermal drug?
Not all drugs are suitable for transdermal absorption. Please remember this! I have heard of lots (and lots) of drugs that are being prescribed that have not been tested, and are told that "they should be absorbed" without any validation. Please...don't!
Medications must be:
1. Small (Phenobarbital is 232 g/mole)
2. Given in doses less than 50 mg/dose (we've pushed this margin with another study)
3. Lipophilic
4. TESTED, even if they meet the above criteria, to ensure they're actually absorbed in the target patient. (Example: we needed a phenobarbital dosage 3x the standard oral dosage to achieve similar serum concentrations.)
So, should we give transdermal phenobarbital or not??
Short answer...with caution.
This study was designed as a crossover study in which 9 epileptic cats received oral phenobarbital for 14 weeks, followed by transdermal phenobarbital for 14 weeks. We found that the phenobarbital dosage did not correlate with the serum concentration, we had more break through seizures and significantly more dose adjustments in the transdermal phase when compared to the oral phase. Bummer, right? That said, I do prescribe it for epileptic cats as long as the owners are comfortable and made aware of the risks of failure.
Bottom line...
If you give a standard oral dose of phenobarbital ( 3 mg/kg) you can predict the serum concentration. If you give a standard transdermal dose of phenobarbital (9 mg/kg) you CANNOT predict the serum concentration. This is also true with dose adjustments. If the cat is showing clinical signs of sedation and the dose needs to be reduced you cannot predict the new serum concentration with a calculation, like you can with oral. This single fact was linked to why we had so many more breakthrough seizures and more dose adjustments during the transdermal phase.
If you use transdermal phenobarbital, prepare the owners that it might not control seizures. To quote myself " ...consistent monitoring of seizure control and serum phenobarbital concentrations, along with appropriate client counseling, is recommended when prescribing transdermal phenobarbital."
Despite the increased number of seizures, and greater number of trips to the vet office, clients preferred the transdermal administration MORE than the oral administration. I sympathized (who wants to give oral meds to a cat?) so my research team and I developed a novel phenobarbital formulation that is applied to the paw and licked off, instead of absorbed. Topical application (not oral...yay!) with oral absorptive pharmacokinetics. More to come on that later!
Have a great week and keep those consults coming!