Just diagnosed with cushing, unsure if I should start treatment

[dew_nay]

I am glad to find this site. My dog, Kooky, a 13yo chihuahua was diagnosed with cushing about 2 months ago. It was confirmed through LDDS test, and also on the ultrasound, my vet found her liver is enlarged and both adrenal glands too were large.

As for clinical signs, it is acceptable to me. She sleeps with me in the room and I don't even need to bring her out middle of the night to urine, she can hold her urine. Her daily water intake is not very excessive either (less than 1oz per pound per day). She doesn't urinate that much either. But she does have some signs like her skin is thin, slow growth of hair and potbelly.

Her ALP and ALT levels are elevated too. Two months ago, ALP was 507 u/l (range 20-150) and ALT 164 u/l (range 10-118). Today, both are even higher with ALP at 690u/l and ALT 203 u/l. Are these level way out of the charts?

I have been very very hesitant to put her on Trilostane which my vet recommended two months ago. The reason I am so hesitant is largely because of the very adverse side effect of the drug.

I am wondering what if I don't put her on Trilostane. Would her lifespan be roughly the same? Would the elevated ALP/ALT level lead to something even more serious than Cushing?

I am just confused. I guess my primary question is should I start her immediately on Trilostane or start her later when either the ALP/ALT level are so off the chart or when her clinical signs get a lot worst?

I am unsure what other information you need. As for the dosage my vet recommended, it is 3mg twice a day for my dog (she weighs 6.4 pounds).

[Squirt's Mom]

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[Roxie]

Hello sorry to hear about Kooky. I am in almost your exact position. My 15 year old dog was just diagnosed last week and I can't decide if we should start her on vetoryl or not. I've read of a lot of side effects and healthy dogs passing on in the trials. It seems most of the ones who died were on 3x and 5x the regular dose but this was in young healthy pups.

Do a lot of reading here there is quite a but of good information. And I am sure you will get some replies from the more knowledgeable members shortly. Good luck.:)

[labblab]

Hello and welcome to you and Kooky! I'm very glad that Roxie's parent has already greeted you because I think you two are in similar situations with similar worries. In fact, I am going to direct you to Roxie's thread for you to read through, because I think many of your same questions are addressed there:

http://www.k9cushings.com/forum/showthread.php?t=7282

As you will see, there are several considerations that can enter into the decision as to when, or if, to start treatment. Once you've read through Roxie's thread, go ahead and ask us additional questions that come to mind.

I do want to add this word of clarification to the worry about death caused by trilostane. It is true that, over time, there have been some deaths of Cushing's dogs associated with physical changes caused by the drug. But the data in the product literature that is given about deaths of healthy "test" dogs is associated with massive overdoses of the medication: 3-5 times the maximum original dosing range of 3 mg. per pound. This means those poor dogs were given between 9-15 mg. per pound of the drug daily for 90 days! :eek: The current recommended initial dose is only 1 mg. per pound. So at the recommended dosing level, that kind of gross overdosing that affected the healthy dogs would never occur.

OK, once again, take a look at Roxie's thread, and then get back with us for further discussion. ;)

Marianne

[dew_nay]

Hello and welcome to you and Kooky! I'm very glad that Roxie's parent has already greeted you because I think you two are in similar situations with similar worries. In fact, I am going to direct you to Roxie's thread for you to read through, because I think many of your same questions are addressed there:

http://www.k9cushings.com/forum/showthread.php?t=7282

As you will see, there are several considerations that can enter into the decision as to when, or if, to start treatment. Once you've read through Roxie's thread, go ahead and ask us additional questions that come to mind.

I do want to add this word of clarification to the worry about death caused by trilostane. It is true that, over time, there have been some deaths of Cushing's dogs associated with physical changes caused by the drug. But the data in the product literature that is given about deaths of healthy "test" dogs is associated with massive overdoses of the medication: 3-5 times the maximum original dosing range of 3 mg. per pound. This means those poor dogs were given between 9-15 mg. per pound of the drug daily for 90 days! :eek: The current recommended initial dose is only 1 mg. per pound. So at the recommended dosing level, that kind of gross overdosing that affected the healthy dogs would never occur.

OK, once again, take a look at Roxie's thread, and then get back with us for further discussion. ;)

Marianne
Marianne, I am so thankful for your reply. And I will be following Roxie's thread keenly. I have got some questions:

1) If I delay Kooky's treatment, would the liver enzyme (ALP and ALT) readings gets worse? Should I take into consideration these readings on when to start treatment?

2) My vet recommends to start her on 3mg Trilostane twice a day (i.e, 6mg daily for a 2.8kg dog). So it is about 2.14mg per kg, is it an appropriate level to start? I see you pointed out 1mg as a start (but you mention the basis is per pound, I suppose it should be per KG?). And from some of the recommended starting dosage by two vets (who seems to be quite prominent practitioners), both of them also have different recommendations. One of them recommended 2mg per KG daily as a start (source:http://www.endocrinevet.info/2012/12/low-dose-twice-daily-trilostane.html). The other vet recommended 1mg per KG daily (http://veterinarynews.dvm360.com/cushings-disease-and-other-adrenal-gland-disorders).

3) Can I know what are the considerations that make you decide to undertake the treatment for your dog when she/he was firstly diagnosed? Was your dog urinating a lot, drinking a lot, ALP/ALT levels are totally out of control that it will become fatal, etc?

4) And then my conviction to start treatment just got a big hit after coming across this thread (http://www.k9cushings.com/forum/showthread.php?t=7255). I know the starting dose is probably on the high side of what you consider it to be at 3.33mg per KG in this case. But then compared to the product insert, it falls under the lower-mid range of the original recommended starting dosage of 2.2mg - 6.7mg. I mean even 3.33mg per kg (which is a lot lower than the 3-5x maximum original dosing range you pointed out) can kill a dog so quickly after just a few days. I just hope this is a very rare case, not a common case. So I guess another question is have you come across often deaths for dogs who start dosage at 2mg/kg?

I am probably just thinking too much about all the bad things that can manifest itself such that the disadvantages are more than the benefits of treating cushing. I agree with you that treating cushing is a trade off against something else. The question is which is the best of the worst option.

[Squirt's Mom]

FYI - 1mg = 2.2kg ;) Also, the starting dose found in the literature has not all been corrected just yet by the manufacturer to reflect the new recommended starting dose of 1mg/lb or 2mg/kg.

[labblab]

Hi again! Thanks very much to Leslie for giving you the converstion of pounds to kilograms. And here are some answers to the questions you've asked (I'll type my answers in red :)):

1) If I delay Kooky's treatment, would the liver enzyme (ALP and ALT) readings gets worse? Should I take into consideration these readings on when to start treatment?

Yes, it is likely that the liver enzyme readings will continue to climb. Ongoing elevated steroid exposure produces fat accumulations in the liver that are associated with elevated readings due to the liver having to work harder to properly perform its functions. I am not a vet, and I am definitely not a liver expert. But my understanding is that these changes do not necessarily constitute overt liver damage, per se. Over time, I think it is possible that some dogs will proceed to experiencing problems with liver function as a consequence of these fatty changes. However, we see dogs here with extremely high enzyme readings for extended periods of time who don't seem to be experiencing any significant functional liver problems at all. So elevated liver enzymes, in isolation, may not necessarily push you into immediate treatment.

2) My vet recommends to start her on 3mg Trilostane twice a day (i.e, 6mg daily for a 2.8kg dog). So it is about 2.14mg per kg, is it an appropriate level to start? I see you pointed out 1mg as a start (but you mention the basis is per pound, I suppose it should be per KG?). And from some of the recommended starting dosage by two vets (who seems to be quite prominent practitioners), both of them also have different recommendations. One of them recommended 2mg per KG daily as a start (source:http://www.endocrinevet.info/2012/12/low-dose-twice-daily-trilostane.html). The other vet recommended 1mg per KG daily (http://veterinarynews.dvm360.com/cushings-disease-and-other-adrenal-gland-disorders).

Yes, 3 mg. twice daily would be a very reasonable starting dose for a dog weighing 2.8 kg. Here's a link to a post on our Trilostane FAQs thread on our Resource Forum that gives more info about the most current dosing recommendations:

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

3) Can I know what are the considerations that make you decide to undertake the treatment for your dog when she/he was firstly diagnosed? Was your dog urinating a lot, drinking a lot, ALP/ALT levels are totally out of control that it will become fatal, etc?

My dog did have moderate elevations in his liver enzymes and also low thyroid readings, but my decision to treat was 100% fueled by his overt symptoms. I now realize he had been suffering from Cushing's for 1-2 years prior to diagnosis. It started with bilateral hair loss on his sides and haunches. Then increased thirst and urination (he had always had a ravenous appetite so that did not really represent a change). Then seeking cool places (tile, hardwood) at all times of year and losing the muscle strength to climb stairs or jump on the couch or in the car. And then finally the non-stop panting, day and night. He Was Miserable!!!!!!! He was actually the first trilostane patient for my specialist and in my area, and I have to tell you, I could not get that first capsule into his mouth quickly enough once he was finally diagnosed. So my feelings about starting the drug were very different from many folks here. I felt as though, without treatment, his quality of life was zero and he was suffering. So I was eager to help him, and grateful that there was medication available. By the way, his liver enzymes never did normalize again, but they stopped worsening after we started treatment.

4) And then my conviction to start treatment just got a big hit after coming across this thread (http://www.k9cushings.com/forum/showthread.php?t=7255). I know the starting dose is probably on the high side of what you consider it to be at 3.33mg per KG in this case. But then compared to the product insert, it falls under the lower-mid range of the original recommended starting dosage of 2.2mg - 6.7mg. I mean even 3.33mg per kg (which is a lot lower than the 3-5x maximum original dosing range you pointed out) can kill a dog so quickly after just a few days. I just hope this is a very rare case, not a common case. So I guess another question is have you come across often deaths for dogs who start dosage at 2mg/kg?

Poor Ruffle's story is definitely a sad one, but it is very, very unusual. I am still not certain exactly what was going on with Ruffle to cause such a crisis in such a short time. It may have been the Vetoryl, or it may have been some other underlying condition. Ruffle's death is a tragedy, but not at all typical of the experiences reported by our members over the years.

I am probably just thinking too much about all the bad things that can manifest itself such that the disadvantages are more than the benefits of treating cushing. I agree with you that treating cushing is a trade off against something else. The question is which is the best of the worst option.

I definitely think it is important for you to know about the risks of treatment in addition to the benefits. But do bear in mind that there are many success stories here, and I hope you'll have the chance to read about them, too. Also, there are additional successes that you don't have a chance to read about here at all. That's because many folks who don't experience any problems with the treatment don't become members and publicly post. They may "lurk" and read, but then they leave us and go on about their normal lives once their dogs are stabilized. Having said all that, please do continue to ask questions and talk about your concerns. That's what we're here for!

Marianne

[dew_nay]

Hi again! Thanks very much to Leslie for giving you the converstion of pounds to kilograms. And here are some answers to the questions you've asked (I'll type my answers in red :)):

1) If I delay Kooky's treatment, would the liver enzyme (ALP and ALT) readings gets worse? Should I take into consideration these readings on when to start treatment?

Yes, it is likely that the liver enzyme readings will continue to climb. Ongoing elevated steroid exposure produces fat accumulations in the liver that are associated with elevated readings due to the liver having to work harder to properly perform its functions. I am not a vet, and I am definitely not a liver expert. But my understanding is that these changes do not necessarily constitute overt liver damage, per se. Over time, I think it is possible that some dogs will proceed to experiencing problems with liver function as a consequence of these fatty changes. However, we see dogs here with extremely high enzyme readings for extended periods of time who don't seem to be experiencing any significant functional liver problems at all. So elevated liver enzymes, in isolation, may not necessarily push you into immediate treatment.

2) My vet recommends to start her on 3mg Trilostane twice a day (i.e, 6mg daily for a 2.8kg dog). So it is about 2.14mg per kg, is it an appropriate level to start? I see you pointed out 1mg as a start (but you mention the basis is per pound, I suppose it should be per KG?). And from some of the recommended starting dosage by two vets (who seems to be quite prominent practitioners), both of them also have different recommendations. One of them recommended 2mg per KG daily as a start (source:http://www.endocrinevet.info/2012/12/low-dose-twice-daily-trilostane.html). The other vet recommended 1mg per KG daily (http://veterinarynews.dvm360.com/cushings-disease-and-other-adrenal-gland-disorders).

Yes, 3 mg. twice daily would be a very reasonable starting dose for a dog weighing 2.8 kg. Here's a link to a post on our Trilostane FAQs thread on our Resource Forum that gives more info about the most current dosing recommendations:

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

3) Can I know what are the considerations that make you decide to undertake the treatment for your dog when she/he was firstly diagnosed? Was your dog urinating a lot, drinking a lot, ALP/ALT levels are totally out of control that it will become fatal, etc?

My dog did have moderate elevations in his liver enzymes and also low thyroid readings, but my decision to treat was 100% fueled by his overt symptoms. I now realize he had been suffering from Cushing's for 1-2 years prior to diagnosis. It started with bilateral hair loss on his sides and haunches. Then increased thirst and urination (he had always had a ravenous appetite so that did not really represent a change). Then seeking cool places (tile, hardwood) at all times of year and losing the muscle strength to climb stairs or jump on the couch or in the car. And then finally the non-stop panting, day and night. He Was Miserable!!!!!!! He was actually the first trilostane patient for my specialist and in my area, and I have to tell you, I could not get that first capsule into his mouth quickly enough once he was finally diagnosed. So my feelings about starting the drug were very different from many folks here. I felt as though, without treatment, his quality of life was zero and he was suffering. So I was eager to help him, and grateful that there was medication available. By the way, his liver enzymes never did normalize again, but they stopped worsening after we started treatment.

4) And then my conviction to start treatment just got a big hit after coming across this thread (http://www.k9cushings.com/forum/showthread.php?t=7255). I know the starting dose is probably on the high side of what you consider it to be at 3.33mg per KG in this case. But then compared to the product insert, it falls under the lower-mid range of the original recommended starting dosage of 2.2mg - 6.7mg. I mean even 3.33mg per kg (which is a lot lower than the 3-5x maximum original dosing range you pointed out) can kill a dog so quickly after just a few days. I just hope this is a very rare case, not a common case. So I guess another question is have you come across often deaths for dogs who start dosage at 2mg/kg?

Poor Ruffle's story is definitely a sad one, but it is very, very unusual. I am still not certain exactly what was going on with Ruffle to cause such a crisis in such a short time. It may have been the Vetoryl, or it may have been some other underlying condition. Ruffle's death is a tragedy, but not at all typical of the experiences reported by our members over the years.

I am probably just thinking too much about all the bad things that can manifest itself such that the disadvantages are more than the benefits of treating cushing. I agree with you that treating cushing is a trade off against something else. The question is which is the best of the worst option.

I definitely think it is important for you to know about the risks of treatment in addition to the benefits. But do bear in mind that there are many success stories here, and I hope you'll have the chance to read about them, too. Also, there are additional successes that you don't have a chance to read about here at all. That's because many folks who don't experience any problems with the treatment don't become members and publicly post. They may "lurk" and read, but then they leave us and go on about their normal lives once their dogs are stabilized. Having said all that, please do continue to ask questions and talk about your concerns. That's what we're here for!

Marianne
Dear Marianne, I truly am thankful for your advice, you have been a great help. Am so glad to find so many experienced members here. Kooky and I will be so grateful to all of you. Now, I am waiting for the drug which will be compounded from the branded Vetoryl. Though I am unsure if I will start her immediately given that she is a happy girl. When I do start, I will update again. Thank you so much once again.

[labblab]

I just wanted to return and tell you that I fear I've given you an incomplete answer re: the mechanisms by which Cushing's causes elevated liver enzymes. You'd think that after as long a time as I've been here, I'd be able to correctly tell you all about cortisol and liver function :o. But after writing what I did earlier, I realized I truly don't have a great understanding, myself, as to the exact mechanism by which the various enzymes may end up with elevations. So I want to research that more on my own, and I'll definitely come back and share that additional info with you, as well!

So stay tuned...;)

Marianne

[dew_nay]

Marianne, I look forward to your findings. Meanwhile, I too asked Dr Peterson some questions on his blog here: http://www.animalendocrine.info/2013/09/working-up-asymptomatic-dog-for.html

Based on his answers, I have more confidence now in proceeding with the treatment.

Meanwhile, I would appreciate if you could advise me what are the things I should look out for and ask about for the follow up ACTH test on the 10th day of treatment with my vet. Any particular questions to ask the vet? Or things I should really note?

Do I have to give her the twice daily dosage exactly 12 hours apart? Or somewhere plus/minus an hour or so within the 12 hrs is ok?

Thank you once again.

[labblab]

Omigosh, that is wild that you posted that question on Dr. Peterson's blog because I actually read it yesterday in my Google search for specific explanations re: liver changes associated with Cushing's! Duh! I should have put it together that the question came from you! :p

Anyway, good for you for writing to Dr. Peterson. And that main blog posting was interesting, even though it didn't answer my specific questions, so my own search continues. :o

Regarding the monitoring ACTH testing, here's a link to a flowsheet prepared by Dechra that helps you know what to watch for:

http://www.dechra-us.com/files//dechraUSA/downloads/Client%20Literature/47902_VETORYL_10mg_Treatment_and_Monitoring_Brochu re_Update_3_2_ps.pdf

One hint: it helps to print out the flowchart because it makes it easier to read and to follow. What you will find is that Dechra generally recommends that unless the initial 10-14 day check reveals that the cortisol is dropping too low, the initial starting dose remains unchanged for the first 30 days. This is because cortisol levels tend to continue to drift downward throughout the first month even when the dose remains unchanged. Therefore, unless a dog shows little to no clinical improvement and a still very high cortisol level at the first testing, it's best to hold off on an increase until you know for certain what the maximal effect will be from the starting dose.

As for the timing, I don't think it is critical that the doses be given precisely at 12-hour intervals. Probably of greater importance is that every dose be given along with a meal. Trilostane needs to be given with food to be metabolized properly. For this reason, on the day of the ACTH testing, the dog should not be fasted and the trilo should be given along with breakfast. Dr. Peterson has another excellent blog piece that addresses that issue.

Marianne

[molly muffin]

Hi, Marrianne and Leslie have been giving you great information, so I just wanted to pop in and welcome you to the forum.

I think the key to preventing a bad episode is to be aware of how Kooky is reacting, any vomiting, diarrhea, wobbly, can't stand, won't eat, do not give the vetroyl and get an ACTH done.

You can also ask for a rescue dose of prednisone just in case.

[dew_nay]

You people are the best. Thank you for all the guidance.

Just a little history on Kooky. She is a survivor, a fighter. Back in 2012, she was diagnosed with chronic heart disease and is now taking 3 types of heart medications: Vetmedin, Forketor and Furmide. Then about 1/2 year later, she has pyometra, an immediate situation where she needs to undergo surgery. When she was first diagnosed with heart failure, the vet gave her 1/2 to 1 year more to go. But today, almost 3 years later, she is still going strong and good. I want her to win this round against Cushings too. And I have faith she will.

I mention the drug Fortekor, I read that Vetoryl has some contraindications with Ace Inhibitor drugs, and Fortekor is an AI drug. My vet wants to stop giving her Fortekor when I start Vetoryl on Kooky. Wonder if any of you came across others with the same situation of having to manage both chronic heart failure and cushings at the same time? And how is their experience like?

[labblab]

That is excellent that your vet is aware of cautions about combining trilostane with ace inhibitors. However, it may not be necessary to completely discontinue the Fortekor. I say this only because we have indeed had other members whose dogs continued taking ace inhibitors after treatment began. The combination may require some dosage adjustment, however, and closer monitoring of potassium and sodium levels.

Probably the technical representatives at Dechra could offer the best guidance in this regard. It may be the case that switching to a different ace inhibitor might be better, or, as your vet is currently thinking, it may be worth discontinuing that class of drugs altogether in Kooky's situation. I'm sure the Dechra reps are well familiar with this issue and would be happy to discuss it in detail with your vet.

Marianne

[dew_nay]

Just wondering, is once or twice dosing better?

[labblab]

Different vets have different preferences, so there is no conclusive answer. Many dogs see desired symptom relief when dosed only once daily, so for the sake of convenience, it is often much easier for owners to adhere to a once-daily schedule, especially since every dose should be given with a meal. For this reason, Dechra still recommends that dogs first be started on once daily dosing. However, some dogs may experience symptom rebound later in the day even when morning post-ACTH cortisol levels are within therapeutic range after the single dosing. So for them, the drug is exiting the body quickly enough that the dose needs to be split and administered at 12 hour intervals.

For diabetic dogs, twice daily dosing is usually always recommended in order to keep the endocrine system under as consistent control as possible throughout the entire 24 hours. Some specialists/researchers prefer twice daily dosing for all dogs for the same reason, hoping that more consistent cortisol control may offer better protection against long-term systemic damage. Plus, dogs being dosed twice daily often end up requiring lower overall daily totals of the drug.

On the flip side, however, we've been warned that dogs dosed twice daily may be at greater risk of seeing their cortisol drop too low, and therefore may require even more frequent monitoring testing. Also, some dogs seem to feel more energetic when their cortisol is actually allowed to increase a bit during the course of a day rather than being maintained at a more consistently flat level.

So as you can see, there is no set answer. The best advice I can give is to start with the regimen recommended by your vet, and then discuss changes down the road if your dog does not respond to the medication as you would wish, or if the dosing schedule presents problems for the owner in some way.

Marianne

[dew_nay]

This is the third day Kooky has started on Vetoryl. So far, she is doing well, appetite is still the same, drinking as usual, energy the same. The only thing I noticed is that her stools are soft, not watery or runny. Just soft. I won't say it is diarrhea, perhaps very mild. The shape of the stools is there, just soft.

Any advice if this is of major concern?

[dew_nay]

From time to time, she does gets soft stools even before treatment with Vetoryl. The first two days the stools were normal, but today, it gets soft.

[Squirt's Mom]

Watch her closely. Loose stools can mean the cortisol is dropping too low but since this is nothing new for her, just watch right now. If this becomes full blown diarrhea, she has nausea or vomiting, loses her appetite stop the treatment and call the vet to let them know what is going on. You are doing a good job of watching and noting changes! That is one of the most important parts of treating this disease. ;)

[molly muffin]

I mix a bit of food in that has a higher fiber content just because my molly too is prone to getting loose stools and even diarrhea at the least little change, even a car ride can do it.

I have found that helps.

[dew_nay]

I mix a bit of food in that has a higher fiber content just because my molly too is prone to getting loose stools and even diarrhea at the least little change, even a car ride can do it.

I have found that helps.
I too gave Kooky some carrots, broccoli, banana too. Her stools is almost back to normal.

[molly muffin]

I mix in some Fromms weight management food, which has a higher fiber content.

Veggies are good for fiber too though.

Poops good now?

[dew_nay]

I mix in some Fromms weight management food, which has a higher fiber content.

Veggies are good for fiber too though.

Poops good now?
Yes, her poops look normal now.

Also, she just gone through her first ACTH test and biochemistry.

There is improvement in her biochemistry numbers. But the ACTH test needs improvement.

ACTH: Basal - 96 nmol/l, post acth - 346 nmol/l

Biochemistry: ALP 611 u/l (previous 690); ALT 130 u/l (previous 203)

Her skin seems to be less thin now and her bruising on her skin also seems to be easing off.

[dew_nay]

I would like some advice. Currently, I am using the branded Vetoryl to compound into smaller dosage. I understand there is a cheaper option of using bulk ingredient to compound. Although, both are Trilostane, is there any difference using bulk ingredient versus branded Vetoryl?

[labblab]

That really is the million dollar question! The short answer is, the active ingredients should be the same and equally as effective as long as the compounders are purchasing their bulk trilostane from a reliable, verifiable source. Historically, the problem in this regard is that it has been up to the individual compounder to perform his/her own quality assurance on the raw chemicals they purchase since compounded products are not FDA-approved and have not been subject to outside testing or product verification. Unfortunately, from the results of general FDA inspections of some compounders, this internal quality assurance is not always performed by all compounders. This is why the FDA recommends that all compounded trilo products use Vetoryl as the basis because then the raw active ingredient will be known to have been supplied by an FDA-approved chemical manufacturer. However, in real life, we know that using Vetoryl as the base can make the compounded product very expensive -- and excessive cost is one reason why owners have turned to compounded products in the first place.

For what it's worth, here's a reply that I posted last year to another member that summarizes the concern that the FDA and certain researchers have regarding the comparable effectiveness of compounded products. Once again, I must emphasize that compounding can be a very helpful and necessary alternative. But these are the reasons why some vets prefer that their patients use Vetoryl when the dosing size and cost permits.


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. And 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...some new legislation has been 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 your vet wants to dose Gracie twice a day, it is true that you will likely need to turn to a compounder to either obtain the brandname 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 the compounder has obtained on their own.

However, 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. 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.

[dew_nay]

Thank you for your advice. I will stick to Vetoryl to play safe.

I asked Dr Peterson as well and here he goes:

"Dr. Mark E. Peterson said...
The brand name product is recommended. Who knows what's really in the bulk product? Sometimes it works and other times it doesn't."

[dew_nay]

Kooky just had her second ACTH test on her 30th day of medication. The results were worst than the first test.

On the first test, the base level was 96 nmol/l and post 346 nmol/l.

The second test done few days ago was 118 nmol/l for base and 566 nmol/l for post acth. The vet did not do a biochemistry test along with the second test because she thinks that it will be a waste of money. But a biochemistry was done during the first ACTH test whereby there is an improvement in her ALT/ALP levels. During both test, I fed Kooky her med with food about 4 hours before the test.

Now, my vet recommend to continue the current dose and do another ACTH test along with a biochemistry test in 50 days time. My vet do not want to increase the dosage yet because Kooky is improving clinically - 1) her bruise which was taking a long time to heal has healed since taking vetoryl; 2) her potbelly looks smaller now, 3) the thinning of the skin looks better, 4) less consumption of water daily (prior to vetoryl, her daily consumption is about 170 ml per day, now is about 140 ml per day).

I would appreciate your advice if any of you have encountered such cases before where the second ACTH on the 30th day is worst than the first. And any advice on what I should do, increase dosage even though there is clinical improvement, etc? If increase dosage, what is the recommended safe increment?

[dew_nay]

I would appreciate any advice what is the safest dosage increment for trilostane if my vet is to suggest an increment if the next acth test still suggest that her cortisol uncontrolled.

In fact, the second acth test on the 30th day of trilostane is worse than the first test on the 10th day. My vet suggests to maintain the current dosage and then see if her cortisol will trend down in 1.5 months time. Hopefully, it will come down on the next test. But if it doesn't, I think my vet may recommend a dosage increase but I wonder if there is any guideline to this increment (by what amount relative to her current dosage to increase)?

I am worried given the toxicity of the drug.

Thank you.

[deannah]

I am not an expert on this disease or the test but just wanted to tell you my experience with the ACTH test. My dog, Puckie's first test showed the following:
Reference Range
base cortisol level: 4.0 ug/dL 1.0 - 5.0
post cortisol level: 19.0 ug/dL 8 - 17

This test was done at around 12 days on 10mg daily of Vectoryl.

2nd test at around 30 days showed a decrease in cortisol so dosage was left at 10 mg daily. Don't have printout of test, only verbal results.

Base level: 1.4
Post level: 6.7

The 6.7 was in the normal range so levels can decrease with time on the same dose. Hope this helps in your decisions. This is such a terrible disease especially finding a knowledgeable vet willing to treat.

Deanna and Puckie

[Squirt's Mom]

Since the signs are improving I would stick with this dose she is on now for the next 2 weeks for sure. Then if the cortisol is still going up, a very small increase, if any. I would want the smallest possible increase tho. The signs count for just about as much as the numbers do. ;)

[dew_nay]

Thank you so much for all the inputs.

The clinical signs are better. Except that her appetite is just as good as before, not sure if it is because of the elevated cortisol or it is just her normal appetite to start with.

I am really worried if the cortisol level isn't controlled and if my vet recommend an increase at that time, I am wondering what increase is acceptable. Unlike the starting dose, I don't seems to be able to find much info on such increase by Dechra except that it says any increase should not be more than 50% of current dose.

I hope the level will trend down by the next test. If it isn't controlled and if my vet recommend an increase, I will make sure it is the smallest possible increase - perhaps no more than 10 or 20% of current dosage.

[labblab]

Hello again! For the benefit of our U.S. members, I am converting Kooky's test results into the units of measurement that are commonly used here.


Initial ACTH monitoring test:

Pre: 3.5 ug/dl Post: 12.5 ug/dl

Second test after 30 days:

Pre: 4.2 ug/dl Post: 20.5 ug/dl

I'm assuming Kooky is still taking 3 mg. of compounded Vetoryl twice daily, is that correct? I can see why you are concerned, because that is a pretty big increase again in such a short amount of time. With a post-ACTH result of 20.5 ug/dl, her cortisol level is again largely uncontrolled. So it is truly a puzzle that her outward symptoms seem to be improving at the same time that her cortisol level is going up. :confused:

In honesty, I don't really know what to make of her results. Since you are using a compounded product, there is always the chance that there is some inconsistency in the dosing. But are you using a new batch of medication, or have you just been continuing with medication from the original batch? If you are still using more of the same capsules that you started out with, then it seems less likely that a compounding inconsistency would be the cause of the higher test results. And again, regardless of the cause for the increase, if Kooky is now doing better with such a higher cortisol level, it makes you wonder whether Cushing's was really the cause of her problems in the first place...

As long as Kooky seems to be doing well, I guess I would just continue on as usual for the time being, too. But I would not wait for 50 days to retest. I would wait no longer than another 30 days, and I would want to recheck her regular bloodwork at that time, as well. It will be very interesting to see whether things have gone up or down at that point in time. And if you see her outward symptoms rebounding before then, I do think a dosing increase would be in order. With a post-ACTH as high as 566 nmol/L (20.5 ug/dl), I think you could probably even go as high as increasing from 3 mg. twice daily to 5 mg. twice daily. Or if you have many more 3 mg. capsules left, you could compromise and bump up to 5 mg. in the morning and stick with your existing 3 mg. in the evening. The makers of brandname Vetoryl now say that the total daily dose does not have to be split evenly in half, but if not, the larger dose should be taken in the morning.

Marianne

[dew_nay]

Hello again! For the benefit of our U.S. members, I am converting Kooky's test results into the units of measurement that are commonly used here.



I'm assuming Kooky is still taking 3 mg. of compounded Vetoryl twice daily, is that correct? I can see why you are concerned, because that is a pretty big increase again in such a short amount of time. With a post-ACTH result of 20.5 ug/dl, her cortisol level is again largely uncontrolled. So it is truly a puzzle that her outward symptoms seem to be improving at the same time that her cortisol level is going up. :confused:

In honesty, I don't really know what to make of her results. Since you are using a compounded product, there is always the chance that there is some inconsistency in the dosing. But are you using a new batch of medication, or have you just been continuing with medication from the original batch? If you are still using more of the same capsules that you started out with, then it seems less likely that a compounding inconsistency would be the cause of the higher test results. And again, regardless of the cause for the increase, if Kooky is now doing better with such a higher cortisol level, it makes you wonder whether Cushing's was really the cause of her problems in the first place...

As long as Kooky seems to be doing well, I guess I would just continue on as usual for the time being, too. But I would not wait for 50 days to retest. I would wait no longer than another 30 days, and I would want to recheck her regular bloodwork at that time, as well. It will be very interesting to see whether things have gone up or down at that point in time. And if you see her outward symptoms rebounding before then, I do think a dosing increase would be in order. With a post-ACTH as high as 566 nmol/L (20.5 ug/dl), I think you could probably even go as high as increasing from 3 mg. twice daily to 5 mg. twice daily. Or if you have many more 3 mg. capsules left, you could compromise and bump up to 5 mg. in the morning and stick with your existing 3 mg. in the evening. The makers of brandname Vetoryl now say that the total daily dose does not have to be split evenly in half, but if not, the larger dose should be taken in the morning.

Marianne
Hi Marianne, thank you for your inputs.

Kooky is indeed taking 3mg vetoryl twice daily and she weighs 2.8kg.

The drug is compounded from the branded vetoryl and both tests, Kooky was fed with the same capsules from the original compounded batch.

What other diseases besides cushing could cause elevated cortisol level?

I will call my vet tomorrow to see if I should get her checked in a month time instead.

[molly muffin]

The ultrasound only showed an enlarged liver and enlarged both adrenal glands right?

And the only abnormal test result was the ALT and ALKP, both elevated.

In light of that, it seems that the cushings is not being controlled on the dose Kooky is currently on. She is at her appropriately level, weighing 2.8kg and on 3mg twice a day, but she might need to be increased based on the last results. So, if at the next test, she is still elevated at what she was on the last ACTH, 20.5 ug post, or it has gone up, then I'd look into an increase.

[dew_nay]

The ultrasound only showed an enlarged liver and enlarged both adrenal glands right?

And the only abnormal test result was the ALT and ALKP, both elevated.

In light of that, it seems that the cushings is not being controlled on the dose Kooky is currently on. She is at her appropriately level, weighing 2.8kg and on 3mg twice a day, but she might need to be increased based on the last results. So, if at the next test, she is still elevated at what she was on the last ACTH, 20.5 ug post, or it has gone up, then I'd look into an increase.
HI Molly, thank you for your advice.

Yes, ultrasound shows both enlarged liver and enlarged adrenal glands prior to the treatment. ALT & ALP are both elevated as well, but show a reduction on the 10th day of treatment.

As for the dosage increment, any idea what is a safe increment to start with if the need arises?

[molly muffin]

Well I wouldn't go up very much, depending on what the results show, max I'd go up is 5mg am and 5mg pm which would be a total increase of 4mg daily, from 6mg to 10mg total.