Pharmaceutical evaluation of compounded trilostane products [Archive] - Canine Cushing's Information and Support Forums

labblab

05-06-2014, 06:34 AM

Hello Monique, and welcome to you. You will see that I have shifted your thread to our "Everything Else" forum. This is because we reserve our main Questions forum for threads containing discussions of specific dogs who are actively facing treatment.

First off, I am so sorry for your loss of Jewel. It is so commendable that you are still maintaing an informative blog. I lost my own Cushpup many years ago, but I feel as though my ongoing participation here is a living memorial to him, and I'll bet you feel somewhat the same. Also, we have another active Dutch member whom I bet will soon be stopping by to welcome you.

Turning to the issue of irregularity in compounded trilostane, we are familiar with this article and have discussed it here previously. If you use our "Search" option with "Audrey Cook" as the keywords, you will find other posts related to this study. For what it is worth, here's a copy of a related reply that I, myself, posted to another member:

I just wanted to add a few thoughts as to why some vets may have a legitimate preference for using brandname Vetoryl over a compounded version of trilostane that is prepared from raw ingredients. It is important to know that compounded drugs are not the same thing as generic equivalents of brandname drugs. And I believe that more vets have become cautious about prescribing compounded trilostane subsequent to news of this 2012 study conducted by Dr. Audrey Cook of Texas A & M University. This study was funded by Dechra, so that may raise the eyebrows of those who are cynical. But Dr. Cook is highly respected internationally both as a researcher and a clinician. These are the study results:

Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from eight pharmacies and assayed for content and dissolution characteristics. Capsules made in-house containing either inert material or 15 mg of the licensed product and proprietary capsules (30 mg and 60 mg) served as controls. Findings were compared with regulatory specifications for the licensed product. Altogether, 96 batches of compounded trilostane and 16 control batches underwent analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance criteria for content. The average percentage label claim (% LC) for each batch ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the controls was 96.1–99.6% (mean, 97.7%). The variance in content of the purchased compounded products was substantially greater than for the controls (234.65 versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for dissolution, but 19 of 96 batches (20%) of purchased compounded products did not. Mean percent dissolution for the purchased compounded products was lower than for controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane content of compounded capsules may vary from the prescribed strength, and dissolution characteristics may not match those of the licensed product. The use of compounded trilostane products may therefore negatively impact the management of dogs with hyperadrenocorticism.

Here's the link for the abstract of this article published in the Journal of the American Animal Hospital Association:

http://www.jaaha.org/content/early/2012/05/18/JAAHA-MS-5763.abstract

The compounding pharmacies that were sampled in the study were not named. So on the face of it, there's no way to know from this study whether any individual compounding pharmacy was problematic in the past, or will be in the future. Historically, there has been no mechanism in place to validate the testing of any compounding pharmacies in terms of efficacy or contents. Validation has not been performed by the FDA, state pharmacy boards (other than Missouri), nor any other regulatory body. This issue has been the focus of congressional concern during this past year, and at the end of 2013, some new legislation was passed by Congress that will affect the regulation of certain large-scale compounders of drugs for human use in the U.S., but not the entire compounding profession.

There are definitely circumstances when there is simply not an available dose of brandname Vetoryl that is suitable given the size or needs of the dog. For instance, if a dog is very small or a vet wants to dose a dog twice a day, you may need to turn to a compounder to either obtain the licensed product to package into alternative capsule strengths (which is what the UC Davis researchers did in their most recent trilostane dosing research study), or else rely on the raw chemical trilostane that compounders have obtained on their own.

Also, the high cost of brandname Vetoryl simply makes it unaffordable for some owners. In that case, they would be left with no treatment option at all in the absence of the less expensive compounded alternative.

Given the results of Dr. Cook's research study, my own personal opinion is this: if I could not afford brandname Vetoryl to treat my dog, or he/she needed a dose or form (liquid) for which Vetoryl is not available, then I would definitely go the compounded route rather than not treat at all. But if I could afford to pay the price for the brandname drug, I would buy it (or at least until my dog had been stabilized on a specific dose of the drug and I could directly compare the results after making a switch). In the long run, that might save money anyway, because I wouldn't run the risk of scratching my head and performing multiple ACTH tests because I couldn't figure out why my dog was having rebounding symptoms or suddenly crashing while supposedly being maintained on the same dose of compounded drug.

Marianne