Trilostane dosage and initial responses?

[Callie's mom]

Thank you to all the knowledgeable people here, I have been reading threads for the last 2 weeks trying to get educated, prior to registering.

My 11 year old boxer, Callie was recently diagnosed with Cushing's after blood and urine lab by my Vet and then an ultrasound and DDST by a specialist. She was put on liquid trilostane from Diamondback beginning last Tuesday. She will see the specialist this coming Wednesday for her first ACTH.

Firstly, I was wondering how high or low her initial dosage is? I'm having trouble relating her liquid dose to the mg of Vetoryl that people talk about. She is 70 lbs and is getting .5 ml twice a day, so 1 ml a day. The bottle says 60mg, but I don't know if that refers to the total contents of the bottle or her daily dose? I see that Vetoryl comes in 10, 30 and 60 mg. Is her dose particularly high, low, or average?

Secondly, I'm trying to assess her response prior to her testing this next Wednesday. From last Tuesday night through Thursday, I saw no response and did not expect to as I have read it can take weeks, even months for the medicine to have optimum results. To my surprise, I started seeing differences on Friday. From Friday to today she seems less panting and probably less thirst and urination, but this is hard to assess because she is even more tired and lethargic (possibly less wanting to bother to get up to drink and pee) than she had been. She also seems very spacy, hard to get her attention. I know I've read of them getting "depressed" on the medicine and don't know if this is what it is. I certainly had hoped that eventually she would become more energetic than before and not less. She is either very tired or possible sore and/or weak. I have told she is arthritic and have read about the cortisol masking this.

Could anyone address what you think about her dosage level and her initial medicine responses? Thanks in advance

Callie's Mom

[celeste]

Hi Callie's Mom
I am very new to this site as well. But I can tell you, you could not have found a better place to be. These loving people are so supportive, it's like having you own personal vet/psychiatrist/ best friend available to you 24/7'. Although I am in no position to give you any answers, I would like to just say hi. My Frankie is an 11 yr old, 90# boxer boy. He was just officially diagnosed Thursday. I started him on 60 mgs of Trilo capsule Friday. I will transistion to 90 mg Tuesday. The first day after his initial dose, I wanted so bad to see a difference, that I perhaps influenced my brain to see something that I know now wasn't really there. From what I have read from these loving people here, some dogs respond quickly, others not so much. Maybe the bigger the dog the longer it takes? Don't know. I am impatient as well, as it is so hard to see out beloved pups suffer. Frankie's panting is driving me insane. He is restless, yet tired at the same time, and at night he seems to pace alot. But I try very hard to repeat what my Mom used to say: This too shall pass. Not much consolation I know. The experts here will fill you in on so much, more than your vet will. And to be armed with so much knowledge, gives you great power. I love my boxer boy so much, he has had a lifetime of illnesses, and I really feel if I hadn't rescued him he would not be here today. And....the love he has given me, well, I would not have known. And what a loss that would have been for me. I hope your Callie gets better soon and stay strong.
Celeste

[Callie's mom]

Yes, I saw of your 11 yr old boxer boy prior to posting this morning. I can attest to your praising of this forum as I have been using it to learn for a few weeks and fortunately from this, know where my vet is going before she gets there. Sounds like you have been a Godsend to your dog, bless you for that. Been with boxers for 56 years, they RULE;)

[addy]

Hi and Welcome,

My pup was on liquid antibiotic so I checked his bottle. On that label it states 25mg-1ml. Your bottle says 60mgs. I am not 100% positive but I think you are dosing at 30 mgs twice a day which is under the 1 mg per pound recommendation, that is good news. It would seem to be per your bottle 60mgs-1ml but, again, I am not 100% positive.

If I am wrong, hopefully, someone will correct me;):)

You can always ring up the vet tomorrow morning to double check the dosage. Never be afraid to ask your vet any questions. You are the best advocate for your dog.

[Callie's mom]

Thanks for the info, very helpful, that must mean that 1 ml is 60 mg, this is not written on the bottle, which would have been helpful. As far as I've learned that would be an average dose. I'm concerned because she seems to be getting too weak in her hind legs. She is slipping on my wood floors trying to sit up. Think I'll call the vet first thing in the morning, I'm worried maybe she needs less medicine.

[StarDeb55]

Welcome to you & Callie! Addy is spot on about the dosage you are giving. 60 mg /1ml of medication, since you're giving 0.5 ml twice daily, each dose should be 30 mg.

Debbie

[molly muffin]

Hi and welcome to the forum. I agree that contacting your vet is a good idea.

I am always a bit leery of the liquid trilostane as for some reason it does seem to be that dogs can get too large of a dose. Maybe go ahead and schedule your follow up ACTH test too.

Sharlene and Molly muffin.

[Callie's mom]

Thanks, my first ACTH is already scheduled for Wednesday, 8 days after first dose, I think today could be too early? I'm trying to figure out if the huge increase in her lethargy and not wanting to do anything but eat and then go back to laying sleeping is because of arthritic pain now intense as the trilostane has cut her cortisol or something else, and if it is arthritic pain, can Adequan or something else help the situation, someone here has said Rimadyl is not an option. Going to skip breakfast dose of trilostane until Vet opens and can talk to them.. .It is awful thinking that what I'm intentionally slipping into her food, unbeknownst to her, is seemingly so detrimental to her. Her quality of life was much better prior to the trilostane kicking in.

[Callie's mom]

I've just read elsewhere on this forum that dogs can have a radical kind of crash from cortisol withdrawal and wondering if that's what my dog is experiencing? Logic indicates a tad less dose of trilostane? Wouldn't a little less trilostane reduce the cortisol a little less to ease the crash? Also she had been on daily cosaqin which I withdrew just thinking something less would complicate things less, now I'm thinking that was a mistake and I should start giving her that again?

[labblab]

Good morning, and I'm sorry you and Callie are having a rough time of it right now. Yes, if it were me, I'd probably restart the cosequin. I'm unaware of any interaction between it and trilostane. And also yes, if arthritis is the culprit, there are some other interventions that can be tried, as well.

It could well be that Callie is suffering side effects from rapidly dropping cortisol and lowering the dose -- even if only temporarily -- may ease her discomfort. But it is definitely best to consult with your vet this morning. I also would want to definitely reconfirm the medication dose. Logic would imply that the 1 ml. amount equals 60 mg. But since the bottle doesn't explicitly state that, I suppose there is an outside chance that the stated 60 mg. amount equals one single 0.5 ml dose, and she is actually getting 120 mg. daily. According to the (unfortunately outdated) dosing chart included in Dechra's published Product Data Sheet, 120 mg. is the recommended starting dose for a dog of Callie's weight. So it is possible that she has been started off on that higher dose. I would reconfirm the actual dose with both the vet and also with Diamondback, just to make sure that there has been no confusion between them. The folks at Diamondback are very nice, and it would actually be helpful to alert them that more complete dosing info printed on the bottle or on an insert would be beneficial to an owner. When you talk to Diamondback, also confirm whether you need to handle the liquid med in any special way: do you need to shake it up before dosing to make sure the trilostane is evenly distributed, should it be refrigerated, are there any warning signs that the liquid may be going bad (like crystallization of the contents), etc.

Please do let is know what you find out and what you and your vet decide to do. Also, when you are able, it would be great if you can get your hands on the actual numbers and written summaries associated with Callie's diagnostic tests. That will give us a frame of reference for moving forward.

Marianne

[Callie's mom]

Thanks for all of that, I'm quite certain with all the help here that i am giving her 60mg a day. I did visit her specialist yesterday and she kept her all day as she had some dehydration and they wanted to give her fluids. They also did an ACTH even though she has only been on trilostane for 5 1/2 days. The vet didn't think even if her cortisol was low, that would account for her symptoms which were sleeping and not wanting to get up except for a total of 30 minutes for the entire day...two meals, 2 pees and poop and that is from making her get up and she is not drinking water and has some muscle weakness, but mainly extreme fatigue. Her panting, excessive drinking and peeing is gone, but replaced with much higher lethargy and not taking water. The vet called me today and said her cortisol was a little low, I believe she said around 4.5, but she could not see how 5 days of low dose cortisol could have made it that low and said she would have expected a reading in the 15s. She wanted me to stop the trilostane beginning tonight and take her in for observation tomorrow. She's suspicious something else is going on and wants to see if she comes back to her pre trilostane behavior. I am very much hoping that my dog is just very sensitive to the trilostane and we might find the sweet spot at a lower dosage. Her appetite is great and I have been putting a lot of water/broth in her food and she was happy to drink a bowl of unsalted chicken broth. Has anyone else seen these type of reactions after so few treatment days?

[Harley PoMMom]

Yes it can and does happen. According to Dechra's product insert,
Hypoadrenocorticism can develop at any dose of VETORYL Capsules. In some cases, it may take months for adrenal function
to return and some dogs never regain adequate adrenal function. You can find this excerpt and the full article here: Dechra's U.S. Product Insert (http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf)

The 4.5 is Callie's post number, right? And the units of measurement for the 4.5 is ug/dl, correct? If so, Callie's post number is not of indicative of Hypoadrenocorticism but it sure did drop fast, and it could just be that Callie is having cortisol withdrawal syndrome.

Hugs, Lori

[labblab]

It is also possible that even though Callie's cortisol technically did not drop too low, some of her blood chemistries may be imbalanced (specifically sodium and potassium). In addition to lowering cortisol, trilostane can also have an effect on aldosterone, too, and it is aldosterone that regulates the balance of those two blood chemistries. I am assuming, however, that the specialist checked her blood chemistries in addition to performing the ACTH?

Also, if you haven't actually done so, I would still double-check the actual dosing that Callie was receiving. We are all just making assumptions based on what seems logical, but we could be wrong. If she was getting a larger dose than expected, that could account for the rapid lowering of her cortisol.

I am surely sorry she is feeling so poorly!

Marianne

[Callie's mom]

Dead on, on the sodium and potassium...u very smart :D I was told about that yesterday, that was the first thing they did and then asked me to leave her for the day for fluids. When I go tomorrow I will take her medicine and show the Vet what I've been giving her to make sure I'm doing it right. Thanks everybody, this is such a great place...a little personal stuff, I had Callie and an 8 year old, my dear Gladys. I got Shirley, our 3rd boxer, now 10 months old, because I knew Gladys couldn't make it once Callie was gone. Then Gladys up and had a big inoperable internal tumor in March and died in April. So I had the odd couple of an 11 year old and 8 month old. I am hoping so much to get some more wear off of old Callie's tires as Shirley started having behavioral issues once losing her playmate and mentor, Gladys. Furthermore in less than 4 weeks I have a 2 week out of the country trip, mostly already paid for, and I so want Callie well enough and stable to be with my live in petsitter:confused:

[lulusmom]

Hi and a belated welcome to you and Callie.

I've just had a minute to read your thread and would like to add my two cents worth of comments.

Firstly, based on the information you provided, Callie is getting 30mg twice a day. When you get liquid meds with a 1ml syringe, 1ml equals the dose stated on the bottle. Therefore, if the dose on the bottle says 60mg, .5ml on the syringe is equal to 30mg. Most experienced vets do start their patients on 1mg per pound so with Callie weighing 70 pounds, her dose of 60mg a day would be considered a good starting point. However, according to a Trilostane Dose Versus Body Weight study conducted by Dr. Edward Feldman and Dr. Philip Kass of UC Davis, they did see a trend that suggests as body weight increases, the amount of trilostane (mg/kg/dose as well as mg/kg/daily dosage) required to control clinical signs decreases. Big dogs in this study, like Cassie, weighed more than 30kg (66lbs). UC Davis' experience with Trilostane has dictated that their treatment protocol be more conservative than most specialists. Their recommended starting dose is lower than 1mg per pound. I have included the url to the abstract of the study below, which you may want to share with Cassie's specialist.

http://www.ncbi.nlm.nih.gov/pubmed/22708554

It is known that dogs are very sensitive to the drug in the first week or two. Dr. Edward Feldman describes sensitivity as being anywhere from the first two weeks to two months. Cortisol can drop like a rock in just a few days, which is why cortisol withdrawal is not uncommon. This alone could explain Cassie's lethargy. Couple that with arthritis being unmasked and you've got a dog that feels pretty crappy. With Cassie's post stim being 4.5 ug/dl at only 5 1/2 days into treatment, you should expect her cortisol to continue to drop at the current dose. As Lori mentioned 4.5 ug/dl is not indicative of hypoadrenocorticism but I believe if you continue with the current dose, Cassie could very well end up in an Addisonian crisis. You have little to no wiggle room at this point and if Cassie were my dog, I would not continue treatment at the current dose.

Your specialist's remark that she would have expected the post stim to be closer to 15 ug/dl at 5 1/2 days is perplexing, especially since I didn't see where an acth stim test was done prior to treatment to establish a baseline. No two dogs respond the same to the drug, including those on lower doses and even with a baseline starting point, there is no way to speculate on where pre and post stimulated cortisol will be at any given point this early in treatment. Is your specialist a board certified internal medicine specialist?

To answer your question, yes, we have seen dogs crash on Trilostane within a few days of starting treatment.

I hope your girl starts to feel better real soon.

Glynda

[addy]

I agree. If Callie were my dog, I would cut that dose in half. Callie's cortisol has no where to go but down.

[Callie's mom]

All I can think of is...knowledge is power!!!, all thanks so much, and aren't we all so blessed to live in this new google age of enlightenment! Great stuff re higher weights and dosages...my partner and i were just discussing how it is still the wild west with professionals using this drug. I can now admit, I starting cheating a day or two ago and cutting the dose by a .005 to a .01 less. Since it is my first instinct to go rogue, I try to control this. I should have a baseline for her cortisol, I just don't know it right now, but will find out tomorrow. Callie had a DDST last Wednesday and her first ACTH on Monday, so I will discuss that with Vet tomorrow. She had no trilostane tonight as vet wanted me to take her off of it and I saw several more energetic signs which made my heart flutter...joining the puppy to bark at our exercise walkers on street...a favorite activity! Vet initially said, let's take her off for 3 days and she wants to eyeball her tomorrow. I am inclined to ask vet why don't we just move her down to .6 or .8 ml a day instead of the 3 days off and see what happens. All of this must be very shocking to their systems and this seems to make more sense to me?

[molly muffin]

You can either reduce dosage, or he might be planning to restart at a lower dosage after a 3 day break?

If I had to guess, it is because the electrolytes were a mess and they had to address that, and he wants her off completely till they know for sure how she is doing.

Sharlene and molly muffin

[Callie's mom]

Electrolytes were I think a little off on Monday, they were fine yesterday. Callie had perked quite a bit and Vet said leave her off of trilostane til Saturday and then restart at 1/4 dose....25ml a day. Last night, it seemed to me, Callie's Cushing's symptoms came back with a vengence, more panting than ever. This was after being off for 1 1/2 days. I proceeded to give her a late meal with .15 ml, which I also gave her this morning. She is good now. I hate to disobey vet, but vet just can't see in theory how such small amounts of medicine could be having such a large effect. I just know what I see.

[addy]

Sometimes what we see may trump the vet :):)

How is Callie today? It can take some tweaking to come up with the right dose.

[Callie's mom]

Thanks for asking! I'm giving her I guess the dosage of a Chihuahua and she (a 70lb dog) is doing really great. Right now I'm giving her .1ml twice a day so 12mg a day. I'm monitoring closely, but this may be her sweet spot dosage

[molly muffin]

So,some big dogs end up on small doses and little dogs on big doses. It all depends on the dog.

Glad she is doing well.

Sharlene and Molly muffin

[Callie's mom]

I think she'd be dead by now if I'd stayed on what she was prescribed, 60mg a day, which the vet says is really low, her cortisol dropped far and fast.

[molly muffin]

It could have been a bad situation but you caught and addressed before that happened. :)

How is she doing?

Sharlene and Molly muffin

[addy]

Trilostane can be a bit unpredictable and I am glad you are ever watchful.:)

We have seen large dogs be super sensitive, small dogs need much bigger doses and some dogs become sensitive to it after a time and need a lower dose. My girl was about 17-18 pounds and was on 50mgs- 30/20 split. So we just never know.

You are doing really well.

[Callie's mom]

Callie, my 70 lb. 11 year old boxer began Trilostane a couple of weeks ago. She is currently getting 15-18mg a day in two doses. She had been started on 60mg a day, but her cortisol crashed and we radically reduced the dosage. She is doing very well, virtually no Cushing's symptoms and good energy, etc. She will get her second ACTH next Monday.

Here is my only current issue. She will not on her own drink hardly any water. Most days I have to make up what I call "chicken water" (a couple of small pieces of cooked chicken, liquified in the blender with a lot of water, given a little more flavor with a dash of store bought unsalted chicken broth, vet said straight broth would be too much) and she will drink that if I sit with her with a bowl. I should be doing this at 5-6 times a day, but have been doing it more a bowl at a time. It is kind of high maintenance. But then she is having in house "accidents". Today I am looking into switching her to can food to help with hydration. Upon discussing this subject with the vet a week ago, she had no ideas about this, she was busy processing why Callie was so sensitive to the Trilostane. Has anyone else here had this problem with Trilostane where there dog has no interest in drinking or have any ideas why she won't drink?

[Squirt's Mom]

MODERATOR NOTE: I have merged your post about hydration with Trilostane into Callie’s original thread. We normally like to keep all posts about each pup in a single thread as it makes it easier for members to refer back to the pup's history when needed. Thanks!

[addy]

As Vetoryl Capsules control the hyperadrenocorticism, there should be a decrease in food and water consumption to normal levels. There should also be resolution of excess urination. If, however, there is a dramatic decrease in appetite or the dog stops drinking water, it could be an indication of a side effect requiring treatment

I'm sure others can speak to this side effect but this quote is from Dechra's literature.

If your vet is unsure how to proceed perhaps your vet could call them. We have the number, I'll go find it. Some of us have also called without waiting for our vet.

I think I would want an ACTH test asap and electrolytes checked.

I'm sorry Callie is having problems.

found it

Here is the phone number 866-933-2472

[Callie's mom]

Thanks, I'll call my vet now

[molly muffin]

What did vet say? Not drinking might indicate that the cortisol is too low. Usually after a crash the safe option is to wait for symptoms to reappear and then test to verify levels are at indicative of needing meds then restart at the lower dose if it is needed. Wondering if she never really bounced back enough.

Hugs
Sharlene and Molly muffin

[Callie's mom]

Vet didn't get back with me yet... I haven't been that (maybe not enough) concerned for her health as I have been making sure she has in one way or another getting fluids. Funny story, for whatever bizarre reason she will not drink from her water bowl by her food, but on good days will go upstairs and drink from a toilet. I bought a toilet base and put a bowl of water and it is in my dining room near her food...hasn't worked:mad:Last week vet had told me to stay off of Trilo for 3 days after she crashed, but after 1 1/2 days Cushing's symtoms returned and I started the lower dose. She is really doing great, just won't drink much on her own, I have to make her water appetizing. Will be interesting next Monday to see ACTH results. I will talk to Vet in AM, early using my indignation that they didn't get back with me today, and make sure they don't want to see her sooner.