Please help - bad reaction with Trilo - don't know what to do next?

[matea]

Hi,

My 13 year old Sheltie was diagnosed with Cushings a little while ago. She also has a mild heart problem, and is taking phenopropalamine every day for slight incontinence she had a while back.

We began her on trilostane last week - 60mgs once a day in a liquid capsule. She began taking it on Friday, did okay Sat but by Sunday and Monday was really lethargic, shaky and unstable and refused food. At her worst, she was hardly moving, couldn't stand up on her own and refused all food - even her favorites like cheese.

We contacted the vet and picked up a bottle of prednisone. After the first dosage she perked up, drank water and ate some, and now after a couple of days on it, she's very perky, energetic and walking better than she has in months. She's also eating quite a bit, which I know is a side effect of prednisone.

She's slowly weaning off the prednisone this weekend and we're talking with our vet again on Monday to discuss options. She suggested maybe giving the trilo every 2 days, as the liquid capsules can't be split up.

I'm hesistant to put her back on it, because of her reaction. Was this a sign of overdosing?

She's 13.5, has arthritis in her joints, and at this point I'm wondering if it's worth it to continue her on any Cushings treatment. She's been taking Cushex drops just for therapy (I know they don't 'cure' anything, but provide some relief). The vet has also prescribed her metacam for her joints.

Anything else I can do for her to make her feel more comfortable? Should we try the trilostane every second day? Would it even work like that?

Any opinions would be great.

Thanks so much!

Matea

[k9diabetes]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi Matea,

How much does your dog weigh?

What testing was done to diagnose the Cushings?

Do you have the results so you could post them?

What you described is a pretty classic looking "too much trilostane" sending the cortisol too low. The pred basically is cortisol and by giving it your bring the levels back up into a healthy range. Glad she responded so quickly and so well!

There is a link here on the forum re Trilostane dosing and that may give you some insight into whether this seems to have been a proper starting dose. But please do post answers to the above questions as it will help people better reply and offer suggestions.

Natalie

[matea]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi Natalie,

She's 17kg - a pretty big Sheltie - so the dosing seems to be in line with what is recommended.

I do have her test results, but I won't be able to get them until this weekend. Basically we had bloodwork done, and it confirmed that she had cushings - and pretty high levels.

Any idea why she's doing 'so well' with the prednisone though? I mean she's better than she has been in weeks/months. I know she can't keep taking it, but it's just nice to see her sort of back to normal.

[frijole]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi - I have never used trilostane, I used lysodren HOWEVER it is my guess that the dosage is too high. Don't worry we have plenty of experts here that can help you. Not all dogs go by "the book". Mine didn't. Its been 3 yrs of treatment and she is doing just fine. So hang in there. Others will chime in soon I am sure.

Glad you found us. And yes - go get the results etc for us. We need it.

Thanks and hugs
Kim

[k9diabetes]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Cushings is not always easy to diagnose and I have seen many times when the diagnosis is wrong. One possibility is that she doesn't have Cushings.

The steroid may also be helping her other problems, like her arthritis, if it's bumping her cortisol levels up above normal. And that would make her feel better. But that too suggests that she wouldn't have Cushings...

That's why seeing the results of her testing and what testing has been done will be very helpful.

Natalie

[matea]

Re: Please help - bad reaction with Trilo - don't know what to do next?

I'll be able to get her results this weekend, they're at my parent's office, so we'll have to go and grab them from there.

I think they performed a full panel on her. I will definitely get the full results ASAP.

She does have some of the other cushings's symptoms such as hair thinning on both sides of the body, pigmentation of the skin, dry coarse coat, and drinking a lot. She also gets shaky in her back end and has trouble getting up at times.

She used to have accidents at night or when she was sleeping/resting, but after taking phenopropalamine, that hasn't happened since.

I'm assuming the steroid is helping her arthritis, she's gone up and down the stairs by herself for the first time in a while.

I'm hoping Metacam will help with that as well, she starts taking that next week.

Thanks so much for your help

[gpgscott]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi Matea,

There are contraintications of Trilo and heart meds.

Trilo is a complicated med.

I really think you need to ask your Dr. why they are prescribing Trilo. esp, with the other conditions/meds.

The right med will make the dog better, not worse.

Scott

[AlisonandMia]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi and welcome from me too.

It does look like the problem could well be too high a dose of Trilostane. Both the symptoms you described and the way the problem appeared around day 3 really suggests that. Although the dose (60mg for 17kg dog) is within Dechra's recommended range, individual sensitivity to the drug does vary and quite a few dogs need more or less than the recommended dose. Some authorities have recently suggested a considerably more conservative starting dose.

From what I've seen here, dosing every second day or for a couple of days and then a day off seldom, if ever, works well. It is vastly preferable to get lower-dose capsules. Very often you can get the caps you have re-compounded into smaller doses. A lot of people who are using 60mg or 30mg capsules also find it really useful to have some 10mg caps on hand for tweaking purposes.

With regards treating her arthritis - Metacam and other NSAIDS (non steroidal anti-inflammatories) can be a bit of a problem in a Cushing's dog - particularly if the Cushing's is not fully controlled. This is because both NSAIDS and cortisol tend to cause inflammation or even ulceration and bleeding in the stomach and the combination can cause serious problems. Often something else such as Tramadol is used for arthritis pain in Cushing's dogs for this reason.

Here's a link to some info on Trilostane: http://www.k9diabetes.com/forum/showthread.php?t=745

Alison

[ventilate]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Hi;
I have to agree with Scott, Kim and Natalie; If your dog is on any heart meds Trilo is contraindicated for some of those meds, I believe it is the ACE inhibiters, as well the signs you saw in your dog does look like it could have been to much meds either to high a dose or possibly the wrong diagnosis so we are anxious to see the test results that diag cushings. There are other conditions out there that mimic cushings the hair loss could be hypothyroid, my dog has Diabetes insipidus in which she drinks tons of water, DI is not Diabetes mellitis the sugar one, DI is when they do not have enough anti duiretic hormone so she drinks and pees and can not concentrate her urine. As the pred helped it appears that it was to low of cortisol causing the problems as well the pred will help the arthritis so that maybe why your pup appears tobe feeling wayyyyyy better.
Hope all stays well and I would hold the trilo for a while, trilo people can give you more info on that. I would also be cautious with the medicam as I believe it is and NSAID and they along with a highcortisol can cause a GI bleed.
How much trilo were you giving?
Sharon

[zoesmom]

Hi and welcome -

What the others have said is right on target. Once we see the test results, it will be easier to tell if it's just too much trilo or a matter of a wrong dx, although her symptoms sure sound like they fit the bill. But those test results are crucial.

I can tell you that my Zoe had the same problems when she first started trilostane - in fact, she got to the point of vomiting and diarrhea, after only two days, even though her dose was in the range for a dog her size. (She also was/is on PPA for incontinence so I don't think that's the problem. PPA is not a heart med, but in humans I know it can affect the heartbeat/heartrate. It's a stimulant.)

Two or three times, we had to stop Zoe's trilostane and after a few days wait each time, we reintroduced at a lower dose. The first couple of reductions weren't enough and within 2 days, she'd start getting sick again. She was started on 180 mg sid, and ended up taking only 45 mg bid, before she could tolerate it. (She weighed 80lbs at the time) It took about 2 or 3 mos. to gradually increase her dose back up to 120 mg. sid because I wanted to be extra cautious, after the rough start. Luckily, I had 15 and 45 mg. tablets at the time so was able to make several different adjustments. (Did you know you can order the exact dosage needed from compounding pharmacies?? I get Zoe's from pethealthpharmacy.com in AZ and it's a great price, compared to what I initially paid 3 years ago.)

Anyway, Zoe did fine, once we took that slower approach. But it's impt. to take several days off before restarting at a lower dose (Dechra recommends 7 - we did 4 or 5, I think.) We have seen some big dogs who needed a much lower dose than normal, and some little guys who wind up on a much higher than standard dose. Each dog is different, so there can be a lot of dose tweaking in the beginning. Zoe is past 3 years on trilostane now, and takes twice the dose that originally made her so sick (she gets 180 mg bid at the present, although she's taken even higher single doses - having been all over the board with trying to find what works best for her.)

So for now, the pred, then when she comes off of that, I'd wait 5 - 7 days before trying a lower dose. Maybe 30 mg would work for her. Even if you have to order some new trilo, hang onto those 60 mg. capsules because you never know if she may end up taking that eventually. Actually, until you can post those original test results, I wouldn't restart the trilo at all, just in case it's a case of misdiagnosis. Sue/Zoe

[matea]

Re: Please help - bad reaction with Trilo - don't know what to do next?

Thanks so much for all your info. First off here are the results that I have:

Endrocrinology test:

Urine Cortisol - 704
Urine Cortisol - Creatinine Ratio - 221.1

I've attached the others as images:



She's not currently on any heart medications.
Currently she's weaning off the prednisone, and we're thinking of trying a lower dosage of Trilo after about a week or so. I have an appt to talk to our vet on Wednesday about it.

So Metacam could be hard on her stomach? I'll have to look into that as well. I just want her to be pain free and comfortable.

Please let me know what the results tell you. I know the cortisol is high.

Thanks,

Matea

[k9diabetes]

Re: Please help - bad reaction with Trilo - don't know what to do next?

So it looks like the only test they did for Cushings was the UCCR urine test?

Do the results you have show the normal range for urine cortisol?

Did they collect the urine for the test at the vet or did you bring it from home?

This is very important for an accurate test - it has to be taken stress-free.

I would never want a dog diagnosed solely on a urine test! It can be used to help rule out Cushings but is not diagnostic for it. So I hope they did an ACTH or, preferably, an LDDS.

Until we can sort this out, I would not give any more trilostane even if the vet wants you to until the Cushings folks here weigh in her diagnosis.

Metacam, like all NSAIDS, can be hard on the stomach. And like most of the NSAIDS, it seems like some dogs have no problem and others have big problems. Our Chris was on Metacam daily for more than four years and tolerated it beautifully. It seems like a bad reaction either happens right away or never happens, not much in between.

Natalie

[matea]

Re: Please help - bad reaction with Trilo - don't know what to do next?

The endocrinology lab report actually says:

Ratios > 60 are supportive of a diagnosis of Cushings.

She also has almost all the symptoms of cushings.

[k9diabetes]

Re: Please help - bad reaction with Trilo - don't know what to do next?

When was the urine sample for that test taken?

[k9diabetes]

Re: Please help - bad reaction with Trilo - don't know what to do next?

From: http://www.kateconnick.com/library/cushingsdisease.html

Diagnosis:
Initially, Cushing's may be generally suspected based on the typical clinical picture described above: a middle-aged or older, potbellied, hungry, thirsty dog with a sparse haircoat. Routine bloodwork may reflect elevated liver enzymes (especially serum alkaline phosphatase), cholesterol, and blood glucose. Some white blood cells may be elevated (neutrofils), and others decreased (lymphocytes, esinophils). A urinalysis may reflect high levels of protein and low specific gravity (dilute urine). X-rays or ultrasound may show an enlarged liver or either enlarged or atrophied adrenals. 50% of adrenal tumors may appear mineralized. Although one could do a CT scan to search for a pituitary tumor, this is not a common diagnostic procedure. All of the above suggest the presence of Cushing's, but specific lab tests can help to further pinpoint a diagnosis. These tests include a urine cortisol/creatinine ratio test, an ACTH stimulation test, and low and high dose dexamethasone suppression tests. There is no single test to diagnose Cushing's, and Cushing's disease is often difficult to accurately diagnose.

Urine Cortisol/Creatinine Ratio Test:

Considered a screening test, this cannot diagnose Cushing's, but it can rule it out. A urine sample is examined for the relative amounts of cortisol versus a normally excreted protein metabolite, creatinine (the latter is used to control for the degree of dilution of the urine). The greater the ratio, the higher the cortisol level. High cortisol in urine is suggestive of high cortisol in the bloodstream. Many conditions other than Cushing's disease can cause false positives, so this test is not considered diagnostic. Nonetheless, if the cortisol/creatinine ratio is okay, the dog is not likely to be Cushingoid, so this is a good screening test.