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Thread: Trilostane Questions for Dr. Bruyette

  1. #11
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    Default Re: Trilostane Questions for Dr. Bruyette

    Quote Originally Posted by David Bruyette View Post
    I think its because pet owners in the United States dont want to handle dog urine

    Dave Bruyette DVM DACVIM
    I'll tell you what....the quick fix for that phobia is to get yourself a cushingoid dog. Why in just a few short months, I guarantee that handling dog pee becomes second nature.....and if you are really lucky like me and have a dog whose PU/PD never resolved with either Trilostane or Lysodren, you'll become quite proficient at catching pee in whatever you can find...even your favorite soup ladle; mopping up pee, even with your good towels if it means getting to it before the other dogs have time to traipse through it and track it everywhere; sliding in pee in your favorite socks or worse yet, the pair with holes in the soles; and last but not least, cussing at pee.

  2. #12
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    Default Re: Trilostane Questions for Dr. Bruyette

    Dr Bruyette:

    Kira is on 40mg of trilostane, twice a day. She has pretty severe arthritis (has a lot of trouble going up and down stairs and getting up). Occasionally, when she appears to be in severe pain, I give her 20mg of metacam. In the past 2 months, I've only given it to her twice, because I just hate giving her a lot of medication. Is there something relatively safe that I can give her when she's having a lot of problems that won't interact with the trilostane?

    thanks,
    Heidi

  3. #13
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    Default Re: Trilostane Questions for Dr. Bruyette

    Dr. Bruyette,

    Another follow-up question has come up regarding the 3-day pooled UCCR analyis. Our experience here has been that our U.S. vets who perform UCCRs typically test using only a single day's sample. If we, as owners, wish to bring in pooled samples for analysis, would the laboratory ranges that our vets normally rely upon still be accurate? Or are the "norms" different for pooled samples than they are for single samples?

    Marianne

  4. #14

    Default Re: Trilostane Questions for Dr. Bruyette

    There should not be a specific issue with trilostane and NSAID's. I would also look at things like glucosamine/chondroiton, adequan, acupuncture, etc for the arthritis.

    Dave Bruyette DVM DACVIM

  5. #15

    Default Re: Trilostane Questions for Dr. Bruyette

    There reference range would be the same.

    Dave Bruyette DVM DACVIM

  6. #16
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    Default Re: Trilostane Questions for Dr. Bruyette

    Dr. Bruyette,

    First let me say that I am very happy to have you as a member of our community and I thank you for agreeing to answer some of our questions. I hope I don't make you regret your decision.

    There have been very few things in my life that have compelled me to look past my nose for a resolution to any crisis but when my first dog was diagnosed with PDH, almost five years ago, I went on a mission to learn absolutely everything I could about the disease. I live, eat and breathe cushing’s and my friends are now loathe to invite me out anymore as they are afraid their eyes may roll back in their head and stay there the next time I start talking about my dogs. I also have a problem with brevity at times so I'll apologize up front for that now.

    Quote Originally Posted by Squirt's Mom
    1. Trilostane is too new, has a much shorter track record than Lysodren, and vets are not as familiar with it.
    Quote Originally Posted by David Bruyette
    While that may be true in the US it is not worldwide and there are numerous publications showing it to be safe and effective. Some bias I think since it was no initially developed in the US.
    The bias you mention is very interesting. I’ve never really thought about that as being a possible factor for a veterinary professional in making his or her decision as to an appropriate treatment. As the developer of the only other drug approved by the FDA for the treatment of cushing’s in dogs, have you noticed a geographical bias with respect to Anipryl?

    As a layperson who spends a great deal of time broadening her backside in front a computer reading members’ threads, I’ve noticed that Trilostane is being prescribed with greater frequency, even before it was approved by the FDA. With the recent FDA approval, I suspect that we will see this trend continue. When I first became a member, almost two years ago, the majority of dogs were treating with Lysodren; however, I believe that is no longer the case.

    In my observations, it looks as though vets with limited experience, with the disease and its treatment, tend to lean toward the one with the least amount of side effects, that being Trilostane. I’ve also noticed that a lot of experienced vets have made a shift toward Trilostane because of its efficacy and safety claims. Then there are others that will probably always prefer Lysodren as they have prescribed it for many years and are comfortable with it.

    As an owner of two cushingoid dogs, a past foster mom to a cushingoid dog and a voracious reader of case studies here, I’ve come to realize that when electing a treatment for our dog(s), it is hugely important that we educate ourselves and consider our vets’ experience and comfort level with whatever drug we are contemplating. It seems to me that an inexperienced vet and an ignorant pet owner are a bad combination for a cushingoid dog and it doesn’t matter if the treatment of choice is Trilostane or Lysodren. We’ve seen it time and time again.

    Would you be willing to tell us which treatment you are more likely to prescribe in the majority of your uncomplicated patients?

    Before moving on to the next subject, I'd like to bring up a question that many of us members have had regarding adrenal tumors. Trilostane is approved for treatment of both pituitary and adrenal cushing's. However, at least anecdotally, we've heard that some specialists believe that Lysodren is the better medication choice for adrenal cushing's because of its direct action on the tissue of the adrenal gland and the associated potential for tumor reduction.

    The Mantis and Lamb study involving 13 or 19 (not sure of the #) dogs with PDH treated with Trilostane, showed enlargement of the adrenals in all cases. While there is no proof that Trilsotane actually facilitiates the growth of a tumor, one would think that this could be a distinct possibility. Are you aware of any additional studies that have been done on this subject?

    Long term and continuing research done by the University of Tennessee shows that Trilostane, over time, will always increase one or more of the intermediates steroid/sex hormones. That doesn't bode well for dogs with functional tumors. With functional adrenal tumors having random secretory patterns involving one or more of the adrenal steroid/sex hormone, wouldn't it be ill advised to treat with Trilostane? We would be very interested in hearing about your experience in this area as well as whether you prefer one medication over the other for treatment of ADH and if so, can you tell us your reasons?

    Quote Originally Posted by Squirt's Mom
    2. Pups on Trilo seem to have inappetence issues; some fairly quickly, some after being on it for a time.
    Quote Originally Posted by David Bruyette
    If you look at the data with respect to op-DDD and trilostane inappetance can occur with both and is usually less frequent, less severe and more rapidly reversed with trilostane.
    I do understand that inappetance can occur with both drugs but honestly, we members have seen a disproportionate number of dogs on long term Trilostane treatment that have unexplained loss of appetite and accompanying weight loss. Have you ever run across this phenomenon in your practice?

    Quote Originally Posted by Squirt's Mom
    5. Shaking and muscle weakness either increases or suddenly appears after starting Trilo.
    Quote Originally Posted by David Bruyette
    Again the data does not support this.
    I believe there is data that may support this. There were dogs that were withdrawn from initial studies (See Nada 141-291) and labeled as treatment failures due primarily to collapse, lethargy, inappetance, and trembling. The number of dogs labeled as failures may have been small in comparison to the study group, but these side effects didn't sound like the normal side effects that quickly resolve by withholding treatment. Per Arnolds Veterinary Products "Summary of Product Characteristics" for Vetoryl (paragraph 4.6 - Adverse reactions) states that Lethargy, vomiting, diarrhea and anorexia have been seen in dogs treated with trilostane in the absence of evidence of hypoadrenocorticism. We have had a number of members who have or are treating their dogs with Trilostane who could attest to this. They report these symptoms after longer term use and with post stimulation numbers being within acceptable range. Trembling is also included in the Dechra package insert as being a common side effect and we have had many, many members who report constant tremors, especially noted during times of rest.

    With reference to dogs with PDH being treated with Lysodren, Dr. Johnny Hoskins (Geriatrics and Gerontology of the Dog and Cat) cites that decreasing plasma cortisol levels may allow the pituitary growth to proceed without inhibition. Is this true in your experience? Some of us here do wonder if perhaps some of the adverse reactions, particularly the inappettance, weakness and tremors, aren’t due to an enlarging macrotumor as opposed to a drug reaction. Can we have your thoughts on this?

    Quote Originally Posted by Squirt's Mom
    6. The attitude that Trilo is a "safe" drug with no side effects.
    Quote Originally Posted by David Bruyette
    It is safe. Thats it was approved. Does it have side effects? Yes, and those are clearly listed on the package insert and in scientific publications.
    I believe that Leslie’s observations are representative of many here that have seen an increasing number of members who have reported a variety of side effects. I am one of those members. I have two cushingoid dogs, one with PDH involving elevation of all intermediate steroid and sex hormones. She is a wee 4.5 pounds and we started her treatment with Lysodren. Although she did very well on Lysodren, I decided to switch her to Trilostane after reading much about it having less side effects. A year into treatment on Trilostane, she lost the re-growth of coat attained with Lysodren and after another a year, a UTK adrenal panel showed a remarkable and very frightening increase in elevation of all intermediate steroids/sex hormones. Do you have concerns about prescribing Trilostane for dogs that have significant elevations in intermediate steroid/sex hormone levels? In those instances, do you recommend an alternative treatment?

    Quote Originally Posted by Squirt's Mom
    Finally, why are Trilostane and Anipryl the only drugs approved to treat canine Cushing's? Lysodren has been around and in use much longer, yet has not been approved.
    Quote Originally Posted by David Bruyette
    No one has tried to get op-DDD approved for use in the dog. I doubt anyone will as there would be huge hurdles to overcome given its derivation (op-DDT), manufacturing issues, safety profile and the availability of other drugs with equal efficacy and higher safety.
    Since op-DDD (Lysodren/Mitotane) is a legitimate off label drug and since it was the government’s extensive testing of op-DDD on dogs that paved the way for approval of the drug for use in humans, would anybody be motivated to seek approval, regardless of the hurdles? With respect to efficacy, is there any other drug, besides Trilostane, that is as effective as op-DDD?

    Thank you for your time.

    Glynda

  7. #17
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    Default Re: Trilostane Questions for Dr. Bruyette

    Bumping this up.

  8. #18
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    Default Re: Trilostane Questions for Dr. Bruyette

    Quote Originally Posted by lulusmom View Post
    Bumping this up.
    Quote Originally Posted by lulusmom View Post
    Dr. Bruyette,

    First let me say that I am very happy to have you as a member of our community and I thank you for agreeing to answer some of our questions. I hope I don't make you regret your decision.

    There have been very few things in my life that have compelled me to look past my nose for a resolution to any crisis but when my first dog was diagnosed with PDH, almost five years ago, I went on a mission to learn absolutely everything I could about the disease. I live, eat and breathe cushing’s and my friends are now loathe to invite me out anymore as they are afraid their eyes may roll back in their head and stay there the next time I start talking about my dogs. I also have a problem with brevity at times so I'll apologize up front for that now.





    The bias you mention is very interesting. I’ve never really thought about that as being a possible factor for a veterinary professional in making his or her decision as to an appropriate treatment. As the developer of the only other drug approved by the FDA for the treatment of cushing’s in dogs, have you noticed a geographical bias with respect to Anipryl?

    As a layperson who spends a great deal of time broadening her backside in front a computer reading members’ threads, I’ve noticed that Trilostane is being prescribed with greater frequency, even before it was approved by the FDA. With the recent FDA approval, I suspect that we will see this trend continue. When I first became a member, almost two years ago, the majority of dogs were treating with Lysodren; however, I believe that is no longer the case.

    In my observations, it looks as though vets with limited experience, with the disease and its treatment, tend to lean toward the one with the least amount of side effects, that being Trilostane. I’ve also noticed that a lot of experienced vets have made a shift toward Trilostane because of its efficacy and safety claims. Then there are others that will probably always prefer Lysodren as they have prescribed it for many years and are comfortable with it.

    As an owner of two cushingoid dogs, a past foster mom to a cushingoid dog and a voracious reader of case studies here, I’ve come to realize that when electing a treatment for our dog(s), it is hugely important that we educate ourselves and consider our vets’ experience and comfort level with whatever drug we are contemplating. It seems to me that an inexperienced vet and an ignorant pet owner are a bad combination for a cushingoid dog and it doesn’t matter if the treatment of choice is Trilostane or Lysodren. We’ve seen it time and time again.

    Would you be willing to tell us which treatment you are more likely to prescribe in the majority of your uncomplicated patients?

    Before moving on to the next subject, I'd like to bring up a question that many of us members have had regarding adrenal tumors. Trilostane is approved for treatment of both pituitary and adrenal cushing's. However, at least anecdotally, we've heard that some specialists believe that Lysodren is the better medication choice for adrenal cushing's because of its direct action on the tissue of the adrenal gland and the associated potential for tumor reduction.

    The Mantis and Lamb study involving 13 or 19 (not sure of the #) dogs with PDH treated with Trilostane, showed enlargement of the adrenals in all cases. While there is no proof that Trilsotane actually facilitiates the growth of a tumor, one would think that this could be a distinct possibility. Are you aware of any additional studies that have been done on this subject?

    Ok this has me concern. How do I find out what medication do I give Tessie. I thought it would be Vetoryl, but the more I find out about cushings the more confused I get of what to start her on.


    Long term and continuing research done by the University of Tennessee shows that Trilostane, over time, will always increase one or more of the intermediates steroid/sex hormones. That doesn't bode well for dogs with functional tumors. With functional adrenal tumors having random secretory patterns involving one or more of the adrenal steroid/sex hormone, wouldn't it be ill advised to treat with Trilostane?
    I really want to know about this question being asked.

    We would be very interested in hearing about your experience in this area as well as whether you prefer one medication over the other for treatment of ADH and if so, can you tell us your reasons?



    I do understand that inappetance can occur with both drugs but honestly, we members have seen a disproportionate number of dogs on long term Trilostane treatment that have unexplained loss of appetite and accompanying weight loss. Have you ever run across this phenomenon in your practice?


    I believe there is data that may support this.

    There were dogs that were withdrawn from initial studies (See Nada 141-291) and labeled as treatment failures due primarily to collapse, lethargy, inappetance, and trembling.

    The first day Tes was on Vetoryl, 8 hours later the trembling at rest, standing, lethargy (I didn't know what lethargy dog looked like at the time I do now) Tess had this less then 8 hours later on Vetoryl. How am I going to but her back on this, what drug do I use.

    The number of dogs labeled as failures may have been small in comparison to the study group, but these side effects didn't sound like the normal side effects that quickly resolve by withholding treatment.

    Per Arnolds Veterinary Products "Summary of Product Characteristics" for Vetoryl (paragraph 4.6 - Adverse reactions) states that Lethargy, vomiting, diarrhea and anorexia have been seen in dogs treated with trilostane in the absence of evidence of hypoadrenocorticism. We have had a number of members who have or are treating their dogs with Trilostane who could attest to this. They report these symptoms after longer term use and with post stimulation numbers being within acceptable range. Trembling is also included in the Dechra package insert as being a common side effect and we have had many, many members who report constant tremors, especially noted during times of rest.

    There should be a big sign on the internet when you start looking for answers about cushings and if I should stop the medication even after one day. NOTE TO ME. Stop the medication if you see tremors or your dog shaking at rest if on one does of Vetoryl.

    With reference to dogs with PDH being treated with Lysodren, Dr. Johnny Hoskins (Geriatrics and Gerontology of the Dog and Cat) cites that decreasing plasma cortisol levels may allow the pituitary growth to proceed without inhibition. Is this true in your experience? Some of us here do wonder if perhaps some of the adverse reactions, particularly the inappettance, weakness and tremors, aren’t due to an enlarging macrotumor as opposed to a drug reaction. Can we have your thoughts on this?

    Enlarging macrotumor as opposed to a drug reaction.
    Ok how do I test for this before I but Tes on any drug for cushings?


    I believe that Leslie’s observations are representative of many here that have seen an increasing number of members who have reported a variety of side effects. I am one of those members. I have two cushingoid dogs, one with PDH involving elevation of all intermediate steroid and sex hormones. She is a wee 4.5 pounds and we started her treatment with Lysodren. Although she did very well on Lysodren, I decided to switch her to Trilostane after reading much about it having less side effects. A year into treatment on Trilostane, she lost the re-growth of coat attained with Lysodren and after another a year, a UTK adrenal panel showed a remarkable and very frightening increase in elevation of all intermediate steroids/sex hormones. Do you have concerns about prescribing Trilostane for dogs that have significant elevations in intermediate steroid/sex hormone levels? In those instances, do you recommend an alternative treatment?

    Also would like to know the answer to this.


    Since op-DDD (Lysodren/Mitotane) is a legitimate off label drug and since it was the government’s extensive testing of op-DDD on dogs that paved the way for approval of the drug for use in humans, would anybody be motivated to seek approval, regardless of the hurdles? With respect to efficacy, is there any other drug, besides Trilostane, that is as effective as op-DDD?

    Thank you for your time.

    Glynda
    Thank You DR Bruyette. I am having a crash course in Cushings. Every one here has been so helpful. I have know idea how I found this site, but I am so lucky that I did. Looking forward to your answers. Dottie
    Last edited by Sammie; 07-12-2009 at 01:17 AM.

  9. #19

    Default Re: Trilostane Questions for Dr. Bruyette

    All good questions

    This is what I recommend and there are geographical/personal issues with regards to what drugs to use in dogs with PDH.

    1) For dogs with mild symptoms or for owners where cost is an issue we start with Anipryl for 2 months. If that fails to resolve the symptoms we move on to another drug.
    2) For dogs that failed Anipryl initially or that have moderate to severe symptoms and we dont want to wait 2 months to see improvement we use trilostane.
    3) We only use op-DDD when everything else fails. We and others have approached the FDA in the past about getting op-DDD approved in the dog and there is about zero chance of that happening. Too many side-effects and manufacturing isssues and the drug will probably come off market soon in the US since very few people take the drug.
    4) Any adrenolytic agent or enzyme blocker can raise steroid intermediates to some degree. Whether this is an issue clinically depends on the given dog, the dose of medication used, the duration of treatment and concurrent diseases and/or medications.
    5) Any drug that lowers cortisol levels below normal will raise ACTH levels. In man, this has been shown to accelerate pituitary tumor growth (Nelsons syndrome). Not clear this is an issue in dogs as we see large tumors at the time of initial diagnosis and in dogs on long term therapy.
    6) We recommend that all dogs have a MRI when they are diagnosed with PDH and at anytime they develop a decreased appetite, increased thirst and behavior changes.
    7) In general adrenal tumors are best treated with surgery as medical treatment is palliative only.

    Dave Bruyette DVM DACVIM

  10. #20
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    Default Re: Trilostane Questions for Dr. Bruyette

    Quote Originally Posted by David Bruyette View Post
    7) In general adrenal tumors are best treated with surgery as medical treatment is palliative only.

    Dave Bruyette DVM DACVIM
    Dr. Bruyette, I just wanted to ask a follow-up question in response to your reply re: adrenal tumors. In those situations where surgery is not advisable (due to age, other complicating medical issues, etc.), do you have a preference as to medical treatment? We have been told that some specialists prefer Lysodren for treatment of adrenal Cushing's due to the drug's effect on the adrenal tissue (and possible tumor reduction). Do you have similar thoughts, or is trilostane your first option for adrenal Cushing's as well as pituitary?

    Also, a second question...we have had a few members here who have treated their dogs with trilostane in a compounded liquid suspension. Often, these are wee ones for whom "standard" prepared doses have been inappropriate. Have you had experience with "liquid trilostane," and if so, do you have any hints to offer in that regard?

    Thanks!
    Marianne

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