Adverse reaction to low dose trilostane

[BarnabysMum]

Hello everyone!

I've been eavesdropping on this wonderful group for several days now and just registered. I'm hoping you may be able to help with my question.

My foster dog, Barnaby, is an ancient Beagle x aged probably about 17 - he's a rescue dog so the vet is guessing.

He was diagnosed with Cushing's after a LDDS test, and possibly other tests - I've been unable to confirm (it's complicated). He has all the classic symptoms. As far as I can tell, there were blood tests done about 2 months ago. I asked to see the results but the vet practice has lost them. I understand there are more tests required for a definitive diagnosis, but for the purposes of my question I'm assuming that he does indeed have Cushing's, so hoping you can please bear with me on that for the moment.

I started him on Trilostane on Friday night, 27 December. Barnaby weighs 17kg. The vet prescribed 60mg twice a day. I refused to give him that dose and went to a compounding pharmacy. I gave him 15mg twice a day, i.e. 0.09 mg/kg twice a day, which is slightly less than the recommended lowest dose... yet it appears it was still too much. he had an immediate reaction: drinking much less water and less interested in food. The next day he became very lethargic and decidedly picky about food and slight diarrhoea (no cautions AT ALL about this from the vet). I scoured the internet. When he vomited at 3am on Sunday night I stopped the trilostane.
Since then over the last week he has slowly regained his appetite and energy - and his Cushing's symptoms. But he once again has quality of life - he is living for his walks and his mealtimes. I am endeavouring to get him to the vet for monitoring within the next day or so...still waiting for a reply to my emails!

Without the old blood tests I can't say what state his liver and kidneys were in but assume the vet would not have proceeded with trilostane if the results were bad. (?!) So my question to the group is: Have you encountered such adverse effects with such a low dose of trilostane? What might be the cause? And, subsequent to him stabilising and relevant testing done, should an even lower dose be even considered? I'd like to be pre-armed before I meet with the vet. I feel that at his age quality of life is paramount and would not want to put him through the trauma of unnecessary testing, cage confinement and more medications unless really warranted.
Many thanks for your consideration.
Linda

[frijole]

Linda .... oh how I wish they hadn't lost the test results! You did the absolute right thing by NOT listening to the vet who would have had you give 120 mgs a day to a 17 kg dog (37 lbs) Given the fact that the cortisol lowered immediately as in a day and then you had every single sign of overdose/low cortisol... you can only assume that either that dose is too high OR your dog does not have cushings... which leaves us back to... how the heck did they lose your test results?!

I assume you have not given any more trilostane? The way this is supposed to work is you have a test done so you know where the cortisol is when you start. Then you start and you go back in for testing to see how it is working. :) Well you know the reduced dosage you were on was too much. What you do not know is what the current cortisol level is. You did say that your dog is acting more normal now? Normally you would have to do another acth test prior to making any dose changes.

I guess I would have the acth test done and assuming that cortisol is still high I would see if giving only a morning dose at 15 mg does the trick. (half of where you were). You would do that for a week or two (obviously stop giving it if he becomes ill) and do another acth test.

YOu need to come clean with the vet and tell them you refused to give that high dosage and so they know that your dog went low even on 30 mgs a day! You did the right thing so don't feel guilty! :)

Kim

[BarnabysMum]

Hi Kim and thank you so much for your quick and helpful reply.

Yes I stopped the trilostane and haven't resumed.

Yes in one of my emails to the vet I included the manufacturer's low dose recommendation, plus links to a couple of journal articles discussing the latest regimen. He did not get back to me but told the rescue group contact that he still thinks the dose he recommended was correct. (!)

I will follow up with a phone call to try to get in to see the vet today or tomorrow. Despite my rather pointed emails to him, I need to be reasonably diplomatic with the vet as the rescue group deals daily with the vet practice for their much-needed discounted sterilisations etc. without which they could not manage....we have to tread carefully.

I do have a print out of the LDDS results:

Baseline cortisol: 234 nmol/L
4 hour post low dose dex: 254 nmol/L
8 hour post low dose dex: 261 nmol/L

I gather this is consistent with Cushing's. The vet suspects an adrenal tumour but either way we would not want to operate...... and for the purposes of treatment I understand trilostane would be appropriate - in theory!

Thanks for the advice re halving the dose. I wonder if this low a dose is unusual??
Thanks again.

Regards
Linda

[BarnabysMum]

Hi again
Another quick follow up question, please.
To test Barnaby's current cortisol levels, (10 days after starting, and 7 days after stopping trilostane) should it be a baseline (resting) cortisol level test, OR an ACTH stimulation test? The vet has said to bring him in, the test will only take an hour. Do I assume from that he intends just a baseline test?
Thanks
Linda

[frijole]

Interesting results on the ldds test... I can tell you it is NOT pituitary cushings. I have to go so can't look up to see if it is adrenal cushings but hopefully someone else can check it later. Note this test is prone to false positives so usually there is additional testing done.

I always had the full acth test done. Again I will defer to someone that has just done the baseline to see if they think that is sufficient in your case.

I understand the need to be diplomatic but at the same time that dosage could have killed your dog. Not to be blunt but I am totally serious! I am so glad you did your own thing and am confident you will manage just fine. Good luck! Kim

[doxiesrock912]

Hello,

17 years old! Good for Barnaby!!!

I also suggest that you do the full ACTH test please. It's more accurate and you really need accuracy at this point, not maybes.

How is Barnaby now?

[BarnabysMum]

Hello Valerie and Kim

I've booked an ACTH test for tomorrow.

Yes I agree that the full dose recommended by the vet might well have killed poor old Barnaby. I'll be seeing the vet tomorrow prior to the test and will make clear my concerns, as there are all the other dogs in the future to be considered too.

Barnaby is almost his old pre-trilostane self. Still not drinking as much nor eating quite as enthusiastically (i.e. not inhaling his food :-)) but is enjoying his walks - rather doddery but that's usual - and seems alert. He has improved every day.

The test results will be interesting. I will also ask for full blood tests.

Linda

[doxiesrock912]

Linda, I'm so glad that Barnaby has improved!
Please insist that the vet follow the links that you have provided. There is no room for error when it comes to these medications.

It is especially important to be honest with your vet because the optimum test result ranges are different for a dog being treated with meds to one that is not.

[labblab]

I do have a print out of the LDDS results:

Baseline cortisol: 234 nmol/L
4 hour post low dose dex: 254 nmol/L
8 hour post low dose dex: 261 nmol/L

I gather this is consistent with Cushing's. The vet suspects an adrenal tumour but either way we would not want to operate...... and for the purposes of treatment I understand trilostane would be appropriate - in theory!

Hello and welcome from me, too! For the purposes of our U.S. readers, here are the LDDS results converted into ug/dl:

Baseline: 8.5
4-hour: 9.2
8-hour: 9.4

These are very high numbers in comparison to many we've seen. I wonder whether Barnaby was very highly stressed at the time the testing was performed and that may have skewed the results? On the face of them, though, they are consistent with Cushing's, and actually they could be associated with either the pituitary or adrenal form of the disease. There is no way to distinguish between the two based on these results. To know for certain, you would need to pursue some additional testing, such as an abdominal ultrasound. However, I understand why that may be a moot point since surgery is not an option, regardless. And you're right that trilostane is prescribed for both types of the disorder.

I do think it is surprising that Barnaby had such an immediate reaction to that dose of trilostane. The only suggestion I would have for moving onward is to try even a much lower dose to begin with -- say, maybe 15 mg. just once a day. To be honest, if it were me, I would probably want to try using brandname Vetoryl this time around -- probably starting at just 10 mg. once in the morning ( that's their smallest capsule strength). I am always a bit leery when I hear about extreme reactions to compounded products. A recent study conducted here in the U.S. demonstrated that some compounded products here varied considerably from the dosage for which they were labelled. If Barnaby still reacts poorly to such a small dose of Vetoryl, I think you'd have pretty strong confirmation that, for whatever reason, he cannot tolerate the drug.

Marianne

[labblab]

Just wanted to add, here's a link that will help you interpret those LDDS diagnostic results:

http://veterinarymedicine.dvm360.com/vetmed/Medicine/ClinQuiz-Interpreting-low-dose-dexamethasone-suppr/ArticleStandard/Article/detail/580093

Marianne

[molly muffin]

Hello and welcome from me too.

Just a quick question, did the vet rule out diabetes and thryoid? They both can present with the same symptoms as cushings and if there is any other kind of nonadrenal illness present, that might affect the LDDS results too.
If he doesn't Have cushings, then an immediate reaction to the trilostane might be seen.
What to the rest of you (marianne, kim, glynda) think?
Of course if these and kidneys have been ruled to all be fine and in normal limits then we are back to him having a sensitivity to the trilostane. A low dose can be beneficial if you are looking for Just enough control and good quality of life.
Important to know what the cortisol is at now though.

hugs,
Sharlene and Molly Muffin

[BarnabysMum]

Hello Marianne!

Thank you SO much for your very helpful response.

Barnaby may well have been stressed, although it's hard to tell...he's a very stoic little dog who never complains, never makes a sound...but I can hear the emotion gurgling away in his throat when I cuddle him.

That is interesting information about the compounded products. I started off with one (donated) box of Vetoryl, 30 x 30mg capsules; the compounding pharmacy gave me back 50 x 15mg capsules, with one 30 mg capsule left over - that makes a total of 780mg. So there's 120mg unaccounted for. I assumed the manufacturer's measurements were out (is that unlikely??).....but now from what you've said I'm thinking it would more likely be the compounding pharmacy. However, even if so, it means that that missing 120mg divided amongst the 50 capsules equates to only another 2.5 mg per capsule, so each capsule would have measured about 17.5 mg - which is still a relatively low dose for a 17kg dog. But good to know about!

Thanks so much for your valuable input.

Linda

[BarnabysMum]

Hello Sharlene and Molly Muffin!

Apparently diabetes has been ruled out in the past but I don't know how far back the testing was done. And as the more recent blood tests have been lost I don't know anything else at all. I'm hoping that in today's meeting with the vet I will at least find out what is written in his notes.

What's really interesting is that if it's NOT Cushing's, that would be consistent with an extreme adverse reaction to the trilostane, is that correct?
L.

[molly muffin]

It Could be, but the other option is sensitivity too, or more in the compounded pills than should have been in there, is another option.

I'm hoping your vet has some good notes on little Barnaby. That is so sweet that you can hear the emotion in his throat when you cuddle him.
Beagles just live to be loved and give love. They are quite adorable .
(we have a couple on the forum too) :)

hugs,
Sharlene and molly muffin