Why hasn't Dechra updated the included literature

[Windhammer]

I realize Dechra has released updated starting dosage guidelines (actually this specific document eluded me until today after 2 weeks of visiting the site, it should probably be highlighted in the FAQ sections a little better). Why haven't they also updated the documentation that comes in the box, and goes to the vet? I feel like a human drug would require that update relatively soon after the change - would the FDA regulate this in any way?

[Squirt's Mom]

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[labblab]

Hello and welcome! First, I wanted you to know that I have manually approved your membership so you do not need to respond to an email confirmation notice.

Secondly, re: Dechra's dosing guidelines...Boy, we could write a saga about that! Let me state that I have no connection whatsoever to Dechra, so everything that I write about this subject is solely the product of my own speculation. However, let me start out by quoting a reply that I added elsewhere on the forum just yesterday. Hopefully, it will fill out a bit of the background to the issue.


Thanks so much for relaying the content of your conversation with Dechra's U.S. office. They have been very polite and helpful to many of our members (including myself!), and I am so glad you had a similar experience. However, their response to you regarding the 1-3 mg/lb initial dosing range [printed in the U.S. Product Insert] highlights an emerging "incompatibility" between the published guidelines issued by Dechra U.K. vs. those published here in the U.S.

Just to bore you with a little bit of history :o, back when I first joined this group in 2003, Vetoryl was a medication manufactured by a British company named Arnolds. Arnolds was subsequently bought by Dechra, and Dechra now has a worldwide presence, including a U.S. headquarters. However, Vetoryl is still made in the U.K. To be legally sold there, Vetoryl must be properly registered with their "VMD" (Veterinary Medicines Directorate). To be legally sold in the U.S., Vetoryl is regulated by the FDA. Both regulatory bodies require their own specific filings and published literature re: medication. Until recently, the published initial dosing recommendations for Vetoryl were similar in both countries. However, last year, the official "Summary of Product Characteristics" for Vetoryl filed in the U.K. was revised to reflect this new initial dosing recommendation:


The starting dose for treatment is approximately 2 mg/kg, [or approx. 1 mg/lb] based on available combinations of capsule sizes.

This is an official recommendation, and can be found here (just enter "Vetoryl" in the "Search" window, then click on the SPC for any dosage strength):

http://www.vmd.defra.gov.uk/ProductInformationDatabase/Default.aspx

Likewise, it is this revised "SPC" recommedation that is discussed in the U.K. publication, "Vetsonline," that we often highlight for our members:

http://www.vetsonline.com/news/product-news/140722-new-lower-starting-dose-for-vetoryl.html

This revised recommendation is based on accumulated worldwide research and experience during the past decade, and reflects the current thinking of the majority of the specialists treating Cushing's here in the U.S. as well as elsewhere. It also reflects experiences we have seen here on our forum during this past decade. Put simply, dogs seem to experience fewer unwanted side effects when they are started at lower doses and adjusted upwards if need be, rather than vice versa.

However, the U.S. Product Insert does not reflect language identical to Dechra's revised "SPC" in the U.K. So the folks in Dechra's U.S. office are obligated to verbally relay the original 1-3 mg/lb dosage range that remains published on the FDA-approved insert. However, as they did with you, I believe they usually make a special point in most conversations to also reinforce a newer sentence that immediately follows the stated range, "Start with the lowest possible dose based on body weight and available combinations of capsule sizes." So in truth, this is the same recommendation as that of the new U.K. revisions: start as closely as possible to the 1mg/lb formula.

I know that the U.S. Dechra office will be very happy to talk about the dosing guidelines and the accompanying research experience in great detail with any vet -- probably in even greater detail than they will normally discuss with an owner. So for any U.S. vet who has questions about the appropriateness of starting with a lower rather than a higher dose, I'd encourage the vet to call Dechra directly in order to discuss whether there are individual factors at play that make a higher dose more desirable for any given dog.

...I hope that what I've written above will give you and our other members a better understanding of our reasoning when we advocate for lower starting doses. My personal opinion is that the simplified U.K. literature more accurately represents the current dosing trends followed by most Cushing's experts, and I hope the U.S. literature follows suit before long.

Marianne

Since this is a long enough "intro" to the subject, I'll end this reply at this point and pick up with a second reply to follow.

[labblab]

OK, so to elaborate a bit on the above.

Yes, the FDA does indeed regulate all the printed information that accompanies approved prescription veterinary products here in the U.S., and I believe that is actually part of the issue in terms of speedily altering the printed literature. It is my understanding that no changes can be made to that language without conforming to some type of application/reapproval process. Exactly what that entails, I have no idea. And whether or not Dechra U.S. is actively pursuing reapproval for that dosing language, I also do not know.

However, as of yesterday (when I last checked), the online posting of the language re: initial dosing range on the official Datasheet that accompanies boxes of Vetoryl sold in the U.K. had not been revised, either. So right now, the only "official" place we are seeing this streamlined dosing recommendation is that "Summary of Product Characteristics" filed in the U.K. and revised last October (2014). So there may be similar issues with reprinting the actual package inserts in the U.K., as well.

I do want to point out that the current U.S. Product Insert does carry this specific language, however, in addition to and immediately following the 1-3 mg/lb dosing range:


"Start with the lowest possible dose based on body weight and available combinations of capsule sizes."

I wish the "range" could be ditched entirely. Because obviously, if you start with the lowest possible dose, you are aiming at 1 mg/lb and not 3 mg/lb :rolleyes:. However, at least every box sold here now includes that additional sentence. Dechra also now makes this same recommendation ("Start with the lowest possible dose") in articles and continuing education materials for vets. However, I personally agree that I wish their outreach efforts were even broader.

Your point about adding more clarification about this issue on the FAQs thread is well taken, and is actually something that we are already talking over.

Marianne

[Windhammer]

Thanks for the detail - I actually submitted a question to the FDA Center for Veterinary Medicine as well just to see if they had a comment on it, and will let you know if/what they respond. It seems like Dechra (and whoever makes Cortosyn) are the only ones profiting from the incorrect guidelines by selling twice as much to most people, without regard to possible additional harm to our pets.

I also noticed when looking at the FDA's web page that Dechra's exclusivity on this ends in December, 2015 which I would assume means we may have a chance at an actual "Generic" that could be even cheaper than the compounders can make! May be wishful thinking, but may as well hope for something positive.

[labblab]

I also noticed when looking at the FDA's web page that Dechra's exclusivity on this ends in December, 2015 which I would assume means we may have a chance at an actual "Generic" that could be even cheaper than the compounders can make! May be wishful thinking, but may as well hope for something positive.

Wow, thanks for noticing that exclusivity endpoint! At the time Vetoryl was FDA-approved, the endpoint seemed so far off that I've forgotten to even check on it :o. Yes, that will be great if and when a generic becomes available. However, I suspect pricing for a generic will fall between the current cost of Vetoryl and compounded trilostane. Since generics are mass-produced by pharmaceutical manufacturers, they must maintain FDA approval and meet all the same regulatory standards as the brandname product. I believe this will likely elevate the cost above the amount currently charged by compounding pharmacies who don't need to meet those same testing and regulatory requirements.

Also, generics may actually put an end to widespread compounding of trilo. Once FDA-approved generics are available, my guess is that vets will prefer writing prescriptions for generics instead of compounded trilostane. So it is one of those double-edged swords. Cost will likely be higher than for compounded products, but the medication will be subject to FDA regulatory oversight in the same manner as brandname Vetoryl.

[labblab]

Just wanted to add that as frustrated as I am by Dechra's product inserts, I am equally as frustrated by vets who persist in prescribing high starting doses of trilo even after they've had the newer recommendations brought to their attention. Even after owners have printed out the info for their vets to read, I can't tell you how many times we've had people tell us, "Yes, but my vet says we should still start out with this higher dose." And then the dog crashes, and the vet says, "Gosh, this is the first time I've ever had this happen!" :rolleyes: :rolleyes:

And all we can hope is that one time will be enough for him/her, and the next dog will be started on a lower dose...

Marianne

[Windhammer]

My vet was very up front about being relatively inexperienced with the disease and was completely willing to support the treatment method advised here (and published in the links here by other vets) once I brought it to her attention. Also went out of her way to call the lab to confirm that fasting would not be required based on their testing methods when I mentioned the guidance not to fast the day of the ACTH test also from here.

So thanks to everyone here sharing their experience, we're on day 5 and only noticing what may be small improvements, but hoping day 10 is a bright one!

[labblab]

We'd love it if you'd like to start a new "personal" thread and tell us more about your dog and your journey together! :)

[labblab]

Just wanted to pop back in again to let you and our other members know that we have followed your suggestion and added to our Trilostane FAQs section an expanded explanation re: revised recommendations to start with lower doses of the medication.

Thanks so much for the kick in the pants! We've been talking about this for a long time, and it feels good to finally have it in writing. ;)

http://www.k9cushings.com/forum/showthread.php?p=1251#post1251

Marianne