Newly diagnosed - struggling with Trilostane dose

[sandersson]

Hi Everyone, So glad to have found this site!
Here's our story. Dolly is the oldest of our 3 girls. She turned 13 in August. Around the beginning of the year we began noticing that she suddenly became a "hungry dog" which she has never been before. Out of our 3 she would often just sniff her food and walk away, and often reluctantly eat just so the others couldn't steal it.
It started to become a real problem when she began stealing anything/everything off the counter, and eating things in the house that had never before been an issue...(a metal canister with tea bags in it; a dried star fish). Her other symptoms also began to show, drinking a lot, peeing a lot, panting a lot, her coat got very wirey, some patches of dry skin and she developed a pot belly. Since we had recently gone through the testing with out other dog (who has always been a hungry dog, drank a lot, peed a lot - but all tests came back negative) we guessed what we were dealing with.
I should mention Dolly did have elevated ALP in Oct 2016, but no other symptoms at that time.
They did a LDDS test in June, that came back inconclusive. (Her 8 hour value was not high enough to say she definitely had Cushings).
PRE-DEX 3.2 ug
4 hrs post DEX 2.1 ug
8 hrs post DEX 1.2 ug
In September we had the ACTH done (We live in CA, but had it done in ID where our daughter lives - much cheaper):
PRE 3.7 ug
POST 35.5
They recommended to start on 60mg Trilostane, and we got it from a compounding pharmacy in chew form.
She really didn't seem to show any improvement, and also her symptoms became worse including a skin infection which I know is common, and lost a lot of hair on her back.
We had a second ACTH test done at our local vet in October to see if there was any improvement.
PRE 6.8 ug
POST 12.5 ug
Based on these results our vet recommended we up her dose to 60mg Trilostane twice a day. Since we'd got the compounded chews previous we agreed it would be best to keep her on those in case there is any change in strength compared to the pills. However, when I received the new chews, I (luckily) noticed they were 120mg. the vet in Idaho had made the assumption she would still be on one chew per day. My vet wasn't comfortable with her getting 120mg all at once, and after discussing with the ID vet, he recommended 90mg once day rather than twice daily (he said everything he'd ever seen recommends a once daily dose) After discussing again with my vet, (and also with the compounding pharmacy who said they were comfortable with us cutting the chews in half and still getting the correct dosing) I began cutting the chews into quarters and giving her 90mg once a day.
Last week she was running low on her chews, and quite honestly is not showing much improvement, so we decided to switch to the capsules thinking that the compounded chews may not have the same strength (not to mention it was a pain to have to cut them up and concerned about the actual dosage she was getting).
My vet gave us 2 prescriptions, one with 60 mg capsules, and one with 30 mg capsules. The plan was to put her on 60mg for one month, and if we still don't see improvement, add in the 30 mg. She also said a second option would still be 60 mg twice a day.
I started her on the capsules on Wednesday, so she's had 5 doses up to today, however we have noticed the last couple of days that she is very week and can barely make a short walk to our local park (about 1/4 mile). My first thought was to up the dose to the 90mg, but in the back of my mind I'm also concerned the lethargy/weakness could be due to the trilostane? Did this get worse because we dropped her dose or is it because she is having an Addisons reaction? (I should mention that she is still starving/drinking/peeing...) I'm pretty sure she's ok, but know it can be very serious...so I haven't given her trilostane today yet....Her vet is out today, i could take her in to be seen by someone else but they are obviously not familiar with her case (and would do if she started having other symptoms). I'm going back and forth with this also since my vet is pretty young and I'm concerned that she doesn't have experience in dealing with this. she does consult with the other vets though.
Sorry to be so long winded, but wanted to give all the details.
Any advice is appreciated!

[Joan2517]

No! Don't up the dose. How much does she weigh? Someone more knowledgeable than I am will be along soon to answer your questions.

[sandersson]

I just weighed her, she's 64lbs

[labblab]

Hello and welcome to you and Dolly! I’m so glad you’ve found us although I’m also sorry for the problems you’re experiencing right now. Dolly certainly does exhibit a classic profile of Cushing’s symptoms, so the diagnosis itself seems reasonable. As you already know, though, the immediate issue seems to be the appropriateness of the trilostane dose. Compounded products can be a lifesaver when dogs require doses that can’t be easily accommodated using brandname Vetoryl, either due to size or expense. But it does seem as though there can be a greater risk for variability in actual dosage size or effectiveness in some of the compounded products. Since you’ve now been given 60 and 30 mg. capsules, are you actually using Vetoryl? I’m assuming you are, since compounded products are not legally allowed to duplicate Vetoryl capsule strengths.

Either way, it is possible that the shift to capsule form has altered the manner in which the trilostane is bring metabolized. In such a situation, the greater danger is associated with cortisol that has dropped too low in comparison to the previous dosing. So between your two choices, I think it is far safer to temporarily withhold the trilostane than it is to increase the dose. It’s true that Dolly’s cortisol was not being suppressed sufficiently previously, but right now it’s impossible to know without testing which way her cortisol has gone on the new medication. So to be safe, I’d withhold it for at least 24 hours and see whether you see any improvement. Of course, if she worsens and develops vomiting or diarrhea, she needs to be seen by the vet and re-evaluated immediately.

Just as a sidebar, both once and twice-daily dosing has advocates. Some clinicians prefer one protocol; some prefer the other. We can talk more about that later on. But first things first. And any time you see the sudden onset of weakness or lethargy in a dog taking trilostane, you must first rule out low cortisol as being the cause.

Marianne

[labblab]

Also, one more thought...are you giving the capsules at the same time and same manner as the chewables? Trilostane must be given along with a full meal in order to be optimally metabolized. So if, for instance, the capsule is now given with food whereas the chewable was not, Dolly’s cortisol may be dripping lower on the same dose of medication.

[sandersson]

Thanks so much Marianne, appreciate the info! Yes, giving it to her at breakfast. But...the compounded after cutting the chews up into 1/2's and 1/4's she should have been getting about 90mg per day, so now with the capsules we had dropped to 60mg per day. I just wasn't sure if I would see a change due to the drop that quickly (after just a couple of days). I didn't give her any this morning, and I'll see how she does on her walk today. Thanks again!

[labblab]

Hmmm...it does become a puzzle then, doesn’t it? You’re right, she may well be suffering because her cortisol is starting to spike again. The path forward would seem clearer to me if the weakness wasn’t involved — if it was only rebounding appetite/thirst/urination. But my own Cushpup was very lethargic when his cortisol was uncontrolled, too. So that may be the issue for Dolly, too. Well, let’s see what tomorrow brings and then go from there.

[molly muffin]

I want to say hello to you and Dolly. Marianne covered all the basis. I guess my concern is that with splitting the chews, it is hard to know for sure a consistent dose was being given as opposed to know that she is getting 90mg now? 60 and 30, or is she just getting the 60 mg now?

I would have withheld the trilostane too and see how she does throughout the day. It doesn't hurt to with hold and you can always start back up again.

[sandersson]

beginning last Wednesday I was just giving her the 60mg planning to up to 90 if we didn't see any improvement after 30 days. I didn't give her any this morning.
Thanks,
SallyAnne.

[DoxieMama]

Hello and welcome from me, too! So glad you've found us. Please keep us updated on how Dolly's doing.

Shana

[molly muffin]

Okay, yes I wouldn't up it till you see how she is doing and if removing the meds makes a difference
how is she doing now?

[sandersson]

She seemed much brighter this morning. I spoke to her vet today & she thinks it could be a mild reaction to the trilostane & recommended I try every other day for a week to get her used to it & see how she does. She thinks the capsules are likely more potent than the compounded chews. If she has any more symptoms she will test her electrolytes. If she does ok after a week then I’ll try daily again. She also said one if the side effects is “dull” & that is a perfect description of how she seemed. Thanks for all of your concern! I’ve really learned a lot reading through all of the forum.
SallyAnne.

[AngieB]

Hi, I'm working through getting the correct dosage for my pup too - so sending you encouragement. - Angie (Yogi, 60 lb flat coat currently on 50 mg Vetoryl 2 x per day)

[Squirt's Mom]

Vetoryl (Trilostane) has a very short life in the body - 2-12 hours. So using this drug any less than once a day is useless and a waste of money. I would rather see the vet giving your baby a very low dose every day then increase as needed. It is also possible she is one of those dogs who simply cannot tolerate Vetoryl and will need to switch to Lysodren. ;)

[labblab]

Hmmmm...yes, since you already also have the 30 mg. capsules on hand, it seems to me as though the more logical strategy would be to resume dosing with 30 mg. daily as opposed to 60 mg. every other day. And since Dolly is acting perkier while off the Vetoryl entirely, I’m not sure I’d rush back into treatment yet, anyway. It now seems more likely that low cortisol (rather than high cortisol) was the issue, and I’d probably want to wait at least another couple of days in order to see how she continued to do while off the medication. Ideally, you’d want to test her cortisol level to better judge exactly what’s going on. But in the absence of testing, I’d want to see more consistently normal behavior before restarting the Vetoryl at any dose.

Bear in mind that we are not vets, so I would talk with your vet further before altering her treatment plan. But if Dolly were mine, these are the concerns I would have.

Marianne