Vetoryl (Trilostane) FAQs

[acushdogsmom]

Trilostane is the chemical name for a medication that is being used successfully to treat Canine Cushing's Disease. Worldwide, the only currently licensed veterinary version of trilostane is manufactured in the U.K. by the Dechra Group under the brand name of "Vetoryl." Vetoryl is now widely prescribed in the U.K. and Europe, and can be obtained directly by U.S. residents (limited amount for personal use only) through a U.K. internet pharmacy named Masters Marketing (http://www.mastersmarketing.com). Since Vetoryl (trilostane) has not yet received FDA approval, please see Post #4 below for the FDA's current policy regarding the importation of unapproved drugs for personal use.

[IMPORTANT UPDATE: On 12-15-08, Dechra announced that Vetoryl has been approved by the FDA for distribution in the U.S. beginning January 2009. The remainder of this thread will soon be revised to reflect this new development.]

Dechra's Recommendations Regarding Treatment and Monitoring

Dechra provides published information about Vetoryl, as well as guidelines for its use. At the bottom of this post, you will find an attachment for Dechra's prescribing brochure. This attachment contains helpful general information about the drug, as well as specific treatment and dosing recommendations (special thanks to Jenny ["BestBuddy"] for providing this brochure).

Please make special note of the Treatment and Monitoring Flow Chart on the last page of the brochure -- it provides revised guidelines for treatment goals and dosing changes. In order to convert lab values on the chart from European units (nmol/l) to U.S. units (ug/dl), divide the values reported on the chart by 27.59.

Because the Vetoryl Brochure is in the form of a pdf file, you'll need Adobe Acrobat reader on your computer to view it. Here is a free version of Adobe Reader to download if you don't already have it on your computer:

www.adobe.com/products/ac...dstep.html (http://www.adobe.com/products/acrobat/readstep.html)

However, if you still have difficulty downloading or viewing this Vetoryl Brochure, there are additional resources listed in subsequent posts that contain similar treatment and dosing information, so just keep scrolling down to find them :).

Treatment and Monitoring Recommended by University of California at Davis

Based on their clinical experience with trilostane, the Veterinary School at the University of California at Davis ("UC Davis") has modified some of Dechra's specific treatment and monitoring guidelines. Since there are differences in the two approaches, we suggest you ask your vet whether he/she will be following the guidelines of Dechra, or those of UC Davis. If your vet is following UC Davis protocol, here is a summary of their recommendations. These recommendations are found on page 3 of the following article (special thanks to Glynda ["LulusMom"] for providing it):

http://www.dvmnews.com/dvm/Small+animal+Medicine/Comparing-therapies-for-canine-hyperadrenocorticis/ArticleStandard/Article/detail/460965


The UC-Davis current recommendation is to initiate trilostane therapy at 1 mg/kg once daily. That dose is continued for about one week until a veterinary re-check can be completed.

Owners are instructed to collect a small urine sample from their dog before leaving home the morning of the scheduled re-check prior to trilostane administration. Trilostane should then be given and the dog should be seen by the veterinarian two to three hours later.

The goal of therapy is an owner who is completely pleased with the response. As aids in achieving this goal, both urine and blood tests are indicated. The urine should be checked, at a minimum, for specific gravity, glucose and urine cortisol-to-creatinine ratio (UCCR). An ACTH stimulation test should be started at the time the dog is seen, again about two to three hours after trilostane administration.

The UCCR result should be within the reference interval and the post-ACTH serum cortisol concentration should be between 1.5 and 5.5 mcg/dl.
If the serum-cortisol concentration is within that goal and the UCCR is abnormal, the medication should be given BID [twice daily].
If the serum-cortisol concentration is too high, the trilostane dose should be increased. But if the serum-cortisol concentration is too low, the dose should be decreased.

This approach should be used at each re-check until the dog is doing well.



Attached below is Dechra's prescribing brochure for Vetoryl. It is viewed most easily if you print it out. This is especially true for the two-page Treatment and Monitoring Flow Chart at the end of the brochure.

[acushdogsmom]

Here is a link to Dechra's own Vetoryl website (for those of you who previously obtained Vetoryl and/or related information from "Arnolds Veterinary Products," you will see that Arnolds is now part of the broader Dechra Group). Upon entering the website, you can click on "Data Sheets" for each available capsule strength, as well as other informational summaries, such as "Frequently Asked Questions" and "Living with Canine Cushing's Syndrome." The Data Sheets themselves are in the form of pdf files. If you experience difficulty reading the Data Sheets, you can scroll down to the next post for similar information in "non-pdf" form that may be easier for you to read:

Dechra Veterinary Products, Vetoryl Information (http://www.dechra-uk.com/viewproductdetails.asp?ID=89).

Here is a direct link to Dechra's "Contact Us" page if you have specific questions about Vetoryl or its use:

http://www.dechra-uk.com/contactus.asp.

Also, here is Dechra's page describing how veterinarians can legally import Vetoryl into the U.S. from the U.K. for resale to their patients. Since trilostane has not yet been approved by the FDA for use in the U.S., veterinarians who import Vetoryl for resale must first obtain an "import waiver" (the process is described on this link):

http://www.dechra-us.com/page/vetorylreg.

[acushdogsmom]

The Veterinary Medicines Directorate (VMD) in the U.K. maintains an "Electronic Summary of Product" (ESPC) for all veterinary medicines authorized for use there. Here are links to their summaries for each available capsule strength of Vetoryl. These summaries are not in the form of pdf files, so they do NOT require Adobe Reader in order to view them. However, they DO contain the same dosing and monitoring information found in the Dechra publications listed above :).

Vetoryl 10 mg capsules (http://www.vmd.gov.uk/espcsite/Documents/183023.DOC)

Vetoryl 30 mg capsules (http://www.vmd.gov.uk/espcsite/documents/143065.doc)

Vetoryl 60 mg capsules (http://www.vmd.gov.uk/espcsite/Documents/125773.DOC)

Vetoryl 120 mg capsules (http://www.vmd.gov.uk/espcsite/Documents/125772.DOC)

[labblab]

Excerpted below is the FDA's stated policy regarding the importation of unapproved drugs for personal use. Please note that the full text can be found at:

FDA Information on Importation of Drugs (http://www.fda.gov/ora/import/pipinfo.htm)

The United States Federal Food, Drug, and Cosmetic Act (Act) (21 U.S.C. section 331) prohibits the interstate shipment (which includes importation) of unapproved new drugs. Thus, the importation of drugs that lack FDA approval, whether for personal use or otherwise, violates the Act. Unapproved new drugs are any drugs, including foreign-made versions of U.S. approved drugs, that have not been manufactured in accordance with and pursuant to an FDA approval...

That said, FDA's guidance for coverage of personal importations of unapproved drugs identifies several factors that should be considered by FDA personnel when determining whether to exercise enforcement discretion and refrain from taking action against the importation of unapproved drugs. The General Guidance Section states that FDA should consider not taking enforcement actions against such importation:

"when 1) the intended use [of the drug] is unapproved and for a serious condition for which effective treatment may not be available domestically either through commercial or clinical means; 2) there is no known commercialization or promotion to persons residing in the U.S. by those involved in the distribution of the product at issue; 3) the product is considered not to represent an unreasonable risk; and 4) the individual seeking to import the product affirms in writing that it is for the patient's own use (generally not more than 3 month supply) and provides the name and address of the doctor licensed in the U.S. responsible for his or her treatment with the product or provides evidence that the product is for the continuation of a treatment begun in a foreign country."

The above guidance does not specify that a U.S. citizen may import an unapproved drug only with a prescription from a U.S. licensed physician, or that a foreign citizen may import an unapproved new drug only with a foreign prescription. Rather, to ensure that the importation is for personal use only (and not for resale), and to ensure that the use of the unapproved new drug sought to be imported into the U.S. is supervised and does not represent an unreasonable risk, the guidance provides that the individual affirm in writing that the drug is for his or her personal use, and provide either the name and address of the U.S. licensed physician who will supervise its use or some evidence that the treatment was begun in a foreign country and that the drugs are being imported to continue/conclude the already begun treatment. Thus, while not the only documentation, either a U.S. or foreign prescription, along with an affirmation of personal use, could be supplied as evidence that this factor exists.

The guidance also provides that the importation should generally not represent more than a 3 month supply of the unapproved products. The purpose for this provision is in keeping with the intent that the guidance relate to only drugs for personal use, not commercial distribution. As the document sets forth only guidance, the 3 month limitation is not a "requirement" or a "restriction." If an individual presents evidence that he or she requires more than a 3 month supply for the full treatment of his or her illness, and it appears that the reordering of a one or two month additional amount may be inappropriate, FDA may consider the release of the full amount. Similarly, if a foreign traveler to the U.S. seeks to import unapproved drugs during his or her stay in the U.S., the amount sought to be imported should represent the amount needed for personal use during the U.S. visit. Where the evidence appears to indicate that the drugs may be imported for commercial distribution, the guidance provides that FDA should refuse admission of such drugs.

It must be emphasized that the intent of the personal use importation guidance is to save FDA resources and to generally permit, through the exercise of enforcement discretion, medical treatments sought by individuals that are not otherwise available in the United States (where such treatments are not promoted/commercialized in the U.S.)...

drafted: Marvin A. Blumberg, HFC-170, 4/3/98

[labblab]

There are at least two pharmacies in the U.S. that are compounding and selling their own versions of trilostane for veterinary use. However, the legality of compounding drugs for animals from bulk ingredients is in dispute. It is the position of the FDA that this practice is not legal. However, a recent Texas federal court ruling has challenged some aspects of the FDA's position (the ruling is currently under appeal by the FDA). Other aspects of compounding are also being hotly debated, both in the courts and also in the public arena. Indicative of the high level of interest and concern was the introduction this spring of the draft version of a bill known as the "Safe Drug Compounding Act of 2007" in the U.S. Senate (not yet acted upon). Listed below are three links to help you better understand the basis for the current controversy over veterinary compounding.

A decision regarding using the compounded version of trilostane is one that you must make in conjunction with your vet. However, whenever possible, encourage your veterinarian to prescribe Vetoryl (the licensed veterinary product). Since Vetoryl is manufactured under government oversight in the U.K., it has been subjected to specific testing for safety and efficacy, and is the product upon which all the recommended treatment protocols are based.

1. The first link is to the "Compounding FAQs" (http://www.avma.org/issues/drugs/compounding/faq_compounding.asp) page on the website of the American Veterinary Medical Association (AVMA). Included in the "Veterinary Compounding Brochure" on this same website is the following explanation of the difference between compounded and generic drugs. The Brochure and other AVMA compounding links can be accessed by clicking on the menu bar at the left side of the FAQs page.

Compounded drugs are not the same as generic drugs. Generic drugs are FDA-approved. To receive FDA approval, generic drugs must demonstrate bioequivalence to the "pioneer brand name" drug. Generic drugs can be identified by the ANADA number on their label and by cross-checking with a drug reference, e.g. the FDA Green Book of Approved Animal Drug Products. In contrast, compounded drugs are extemporaneously prepared products that lack FDA approval. The concept is that compounded drugs with their possible flaws are better than no drug at all and suitable for a small patient population.

2. The second link offers a news summary of the current status of related court proceedings: "Despite court ruling, FDA still warning compounders." (http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=394828)

3. The third link is to the FDA's stated position regarding their concerns and the legalities associated with veterinary compounding: FDA Compliance Policy Guide. (http://www.fda.gov/ora/compliance_ref/cpg/cpgvet/cpg608-400.html)

[AlisonandMia]

This thread is soon to be updated in the wake of FDA approval of Vetoryl.

Meanwhile for the latest, see this thread and in particular the last post on that thread (which is where this link will take you): http://www.caninecushings.net/forums/showthread.php?p=87927#post87927

Please note, though, that the info on that thread may not be as accurate as we would like at this early stage - which is why this thread has not been "officially" updated yet. Further things may come to light in the next little while.

Alison