Vetoryl (Trilostane) FAQs

Trilostane is the chemical name for a medication that is being used successfully to treat Canine Cushing's Disease. Worldwide, the only licensed veterinary version of trilostane is manufactured in the U.K. by the Dechra Group under the brand name of "Vetoryl." Vetoryl is marketed in four dosage strengths: 10 mg., 30 mg., 60 mg., and 120 mg. capsules. It is widely prescribed in the U.K. and Europe, and Dechra has recently announced that 30 mg. and 60 mg. Vetoryl capsules have been approved by the FDA for distribution in the U.S. beginning January 2009. Dechra anticipates that 10 mg. and 120 mg. capsules will also receive FDA approval later this year.

It is our current understanding that 30 mg. and 60 mg. Vetoryl capsules are being sold in the U.S. by veterinarians. Also, through March 2009, it appears as though American residents with existing prescription refills are still able to import all four Vetoryl capsule strengths from a U.K. internet pharmacy named Masters Marketing (http://www.mastersmarketing.com). (Please see Post #4 below for the FDA's current policy regarding the importation of unapproved drugs for personal use). However, Masters is no longer accepting new prescriptions for 30 mg. or 60 mg. capsules from U.S. residents.

Additionally, several pharmacies in the U.S. are compounding and selling their own versions of trilostane for veterinary use. For members who obtain compounded trilostane, we encourage you to contact your pharmacy directly in order to determine the effect that FDA approval of Vetoryl may have upon the future availability of your compounded product. (Please see Post #5 below for additional discussion regarding compounded trilostane.)

Dechra's Recommendations Regarding Treatment and Monitoring

Dechra provides published information about Vetoryl, as well as guidelines for its use. For U.S. pet owners, here are links to Dechra's U.S. website and several very helpful diagnostic, treatment, and monitoring resources, as well as contact information in the event that you or your vet have questions.

Dechra's U.S. Website Homepage

Index of Resource Information for Veterinarians

Diagnostic Brochure

Treatment and Monitoring Flowchart

Technical Brochure

Dechra's U.S. Product Insert

Because these resources are in the form of "pdf" files, you'll need Adobe Acrobat reader on your computer to view them. 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

However, if you still have difficulty downloading or viewing these "pdf" files, 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+ani.../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.

Here is a link to Dechra's U.K. 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 will find "Data Sheets" for each available capsule strength, as well as Dechra contact information and other educational summaries, such as "Frequently Asked Questions" and "Living with Canine Cushing's Syndrome."

Dechra Veterinary Products, Vetoryl Information.

In order to convert laboratory values from the U.K. charts and literature (nmol/l) into U.S. lab units (ug/dl), divide the values reported on the U.K. charts by 27.59.

[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

Vetoryl 30 mg capsules

Vetoryl 60 mg capsules

Vetoryl 120 mg capsules

[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

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]

A decision regarding using a compounded version of trilostane is one that you must make in conjunction with your vet. Be aware that compounded versions of trilostane, while in widespread use, are not the equivalent of generics, and do not carry the same U.K./U.S. certifications as does Vetoryl. There are several pharmacies in the U.S. that are compounding and selling their own versions of trilostane for veterinary use. However, the FDA, various compounding pharmacies, and other interested parties are currently involved in ongoing litigation seeking to define the regulatory oversight associated with both human and veterinary compounding.

For additional information regarding the use of compounded medications in the U.S., here are some related links from the website of the American Veterinary Medical Association (AVMA).

"Veterinary Compounding" Brochure
Compounding FAQs
Pharmacology Basics
What are the rules?
Definitions
AVMA Policies

Included in the "Veterinary Compounding" brochure is the following explanation as to the difference between compounded and generic drugs:

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.