Daphne (couldn't tolerate Trilostane) now rests in peace

[AvileeG]

Hello everyone – I am new here and looking for a voice of experience…

Daphne, our 12-1/2-year-old small-dog mix (Shih tsu? hairy hairless Chinese Crested?) was definitively diagnosed with Cushing’s over the summer (we had tested her three years ago, but both the ACTH Stim test and the ultrasound were borderline/inconclusive, so we did not start treatment at the time. She has been on insulin for the past three years for diabetes, assumed to be secondary to the incipient Cushing’s).

We started her on trilostane at the presumably low dose of 1 mg/kg (compounded to 5 mg/ml, so for an 11 pound dog, 1 mg/kg = 1 ml), BID, three weeks ago -- she had a fairly severe reaction after two doses, extreme lethargy (nearly immobile) and trembling/shaking, so we took her off for a day and restarted at half the dose; after one dose at 0.5 ml, she again had a severe reaction. She had been taking a Chinese herb to help with the incipient disease since three years ago, which we figured might have been interacting with the trilostane, so we discontinued the herb, waited a week, and then started again – figuring she is just exquisitely sensitive to this medication, so starting really low. We were shooting for one-quarter of the original dose, but creeping up to it by tiny bits – we started at 0.05 ml and planned on adding 0.05 / day until we got to 0.25 ml (BID).

We ended up going a little slower, because her blood sugar was affected more than we had anticipated, but other than that she had no bad side effects – until yesterday, her second day on 0.2 ml, when she began to have nosebleeds. They would not last very long (fortunately) -- not even long enough to get an ice pack to her nose before they stop on their own -- but in the last 24 hours she has had five nosebleeds, which is something she has never had in her life.

Other than that she seems fine – energy level is pretty good (as good as it gets, considering how much the Cushing’s has wasted her muscles), no appetite problems; only one odd effect of smelling like garlic.

So – what I wonder is if the nosebleeds are something that we could attribute to her body adjusting to the trilostane? Or is it something associated with Cushing’s? Right now we’ve temporarily discontinued the trilostane, because we’re afraid of the nosebleeds getting worse, and we’re waiting to hear back from the doctor… but I would love to know if anyone out there has had any experience with this symptom. (and if you’ve experienced this weird garlic smell, I’d love to know, too).

thank you for any advice!

[labblab]

Hello and welcome to you and Daphne, although I am very sorry for the problems that have brought you here to us. I wish I could offer some answers as to what might be causing these new issues, but neither nosebleeds nor a garlic odor are common or even known reactions to trilostane of which I am aware. A possible link between nosebleeds and Cushing's itself would be high blood pressure -- hypertension can result from effects of elevated cortisol, and hypertension can cause nosebleeds. I have no idea what could be causing the garlic odor.

But it does seem awfully coincidental that all of Daphne's ill effects have coincided with the new trilostane treatment. In honesty, I am a bit worried there may be a problem with your compounded med. I am wondering whether perhaps there is a mistake in the base chemical that was used, or in the concentration, or in some contaminant. I definitely would not give her any more of the liquid at this point. And these reactions are odd enough that if they should worsen -- especially the nosebleeds -- I believe I would seek emergency care if your own vet is not available. Can you check her gums to see whether they seem pink and healthy, or are they blue or mottled in any way?

Is there any chance at all that Daphne could have gotten into any type of poison (like rat or insect poison?). Some of those poisons act by disrupting blood coagulation, and the combo of the nosebleeds and the odd garlic odor would have me worried about that possibility, as well.

Please do update us as to how she's doing, and I certainly hope you'll hear back from your vet promptly.

Marianne

[mytil]

I do agree with Marianne - it could be a coincidence about the Trilostane and the sudden onset of nosebleeding and the garlic odor.

I would seek immediate attention for your pup.

There are numerous things that can poison a dog and cause nosebleeds and the smell of garlic in a garden. Possibly there is something in your garden that contains arsenic (like slug and snail baits and even ant bait).

Please keep us posted
Terry

[labblab]

Terry, now that you mention it, I am wondering about arsenic, too, because it does have a garlic odor and could also cause all the initial problems that Daphne experienced. Thanks for mentioning that!

I wonder if there is any chance that the the compound liquid could be contaminated with it, because the timeline sort of makes sense. There were acute problems when the dose was higher, and then subacute problems that manifested more slowly at the lower dose. I think that's kind of the way that arsenic poisoning works.

For sure I would not give any more of the liquid right now and I would keep it on hand for the possibility of lab analysis if need be.

Marianne

[mytil]

At least it should be looked at. Unfortunately, arsenic is also found in "trace amounts" in a lot of poultry etc under the name of 3-Nitro (Pfizer agreed to withdraw it from the market just this year). http://www.fda.gov/AnimalVeterinary/.../ucm257540.htm.

Please let us know where is your Trilostane compounded! I would contact them to see what the ingredients of the suspension are.

Please keep us posted

Terry

[Squirt's Mom]

How is Daphne this morning? I am worried along with others, concerned this might be a case of poisoning. Praying she is much better!

[AvileeG]

Hello everyone,
Since so many of you here have been so kind and concerned when I posted about Daphne's nosebleed crisis, I figured that now that crisis is ameliorated I ought to more generally introduce her to the forum. Sorry if this is really long, it's been a bit of a saga with her that I'm writing down all at once...

She is a now 12-½-year-old little dog, we have no idea what but we always assumed part shih-tsu or lhasa, lately thinking more toward hairy hairless Chinese Crested (her hair was always pretty thin, even before the Cushing's).

We started testing her for Cushing's in spring 2012, when her liver values started to rise (AlkPhos 890 in April, 1800 in July; ALT 140 in April, 244 in July), at the same time as she was drinking and peeing a lot and we noticed the pot belly. Both the SCTH Stim test and the ultrasound were borderline /inconclusive, so our vet was not ready to start treating her with the usual heavy-duty treatments. At the time, we had an amazing (and amazingly perceptive) holistic doctor (western medicine plus traditional Chinese medicine) who had treated all our babies for many years -- she started her on Si Miao San, hoping that would keep her mild, incipient pre-Cushing's at bay, as well as Denamarin to help her liver.

During that fall she lost a lot of weight while eating everything in sight, then her blood glucose spiked and she was diagnosed diabetic (presumed secondary to the incipient Cushing's) in December 2012, started on insulin January 2013. We started with just a half-unit and worked up from there, so it took a while to get her to her current dosage of 7-½ units, but once we did her liver values came down a lot (though not normal, sill a lot better -- AlkPhos in the 500s, ALT down as low as 99) and things stabilized for a couple of years. It was definitely a relief to see her gain the weight back and get some energy back once we got her blood sugar stabilized — although diabetes can definitely drive you crazy, we get a lot of good advice from our neighbor who is a type-1 diabetic.

In the summer of 2014, we noticed her liver values rising a bit, so our doctor added another liver-support herb, but we didn’t really see her symptoms progressing at the time. We do think now that probably the Si Miao San and other herbs managed to keep the pre-Cushing's at a low level for a while... It wasn't until early this year that we noticed how much her hair was thinning out, and that she was getting steadily weaker and weaker as her muscles deteriorated. This unfortunately coincided with our trusted holistic doctor having to give up her practice and move away (long story); we stayed with the the second doctor, who had also occasionally seen Daphne over the years, for our summer checkups. She took a look at her and advised us to have her re-tested for Cushing's, for which we are grateful (her ACTH Stim test came back 5.1 pre-stim, 30.5 post-stim, which combined with her now-accelerating symptoms looked like enough to start treating) -- but since she is not a holistic practitioner she couldn't advise us on the Chinese herbs and how they might interact with any conventional treatment.

We started her in late August on trilostane at the standard low dose of 1 mg/kg BID (easy, since she’s an 11 lb / 5 kg dog), compounded to 1 mg/ml because they were out of 5 mg pills. After two doses, she had an intensely severe reaction — shaking and extreme lethargy (nearly immobilized), so we stopped the drug for a few days, then restarted at 1/2 the dose (0.5 ml). This time she only had one dose before developing the same severe reaction; and this time we took her to the clinic where they tested her and found her electrolytes way off (potassium high, sodium low, what you might expect with too much trilostane). So we figured she was just immensely sensitive to this stuff...

The impression we got from the doctor was that it was trilostane or nothing, that Selegiline wasn’t even worth trying — and since she is aging fast with this disease, not treating her felt like just giving up on her. So we tried the trilostane again (after more than a week off, and after stopping the Si Miao San), starting at 0.05 ml to work up to 1/4 ml. We had gotten her up to 0.2 ml, seemingly fine — when on the 2nd day at that level she started having sudden and very frightening nosebleeds. We ended up taking her to the emergency room, where they did more blood tests but never found an explanation, aside from ruling out any toxicity.

We had stopped the trilostane, and the nosebleeds diminished and then stopped, about two days after they started... She did also have diarrhea (very severe at the time of the nosebleeds), which started about the time we started that last bout of trilostane.

So last week we did what we should have done months ago, and made an appointment with a holistic doctor recommended by our previous doctor. We saw her last weekend,and she advised us on some strategies for the diarrhea as well as how to go forward with treatment for the Cushing’s. She agreed with us that the nosebleeds must have had something to do with the medication — the timing was just too much of a coincidence — and that since the blood-work showed no sign of toxicity, even though nosebleeds are not a known side effect of trilostane, it is just too much of a risk to try it again.

So we are going to try Selegiline/Anipryl, along with a new herb formula for support. Although it feels a little odd to change doctors while we’re trying to deal with such a difficult disease process, the amount of time she spent with us, closely observing Daphne, felt much more like what we’ve been used to, and we feel like we made the right decision... I do so hope the Anipryl will work, I know it doesn’t with all dogs — but after that episode with the nosebleeds I would be afraid to try trilostane again even if the doctor recommended it (although, heartbreakingly, I did see some signs of increased energy with that extremely low dose). Right now we are still dealing with the lingering effects of the shocks to her system, with the diarrhea still very gradually improving — we would like to get her closer to her "normal" before starting a major new medication, but it looks like we are figuring on starting the Anipryl tomorrow or Saturday at least.

Again, sorry this is so long — thank you so much for reading this, if you've gotten this far!

[Squirt's Mom]

MODERATOR NOTE: I have merged your post giving more detail of her health history into Daphne’s original thread. We like to keep all posts about each pup in a single thread as it makes it easier for members, and parents, to refer back to the pup's history when needed. Thanks!

[molly muffin]

Those nosebleeds where very strange indeed.
Anipryl works in a small percentage of dogs so I hope that it helps Daphne.

Let us know how it goes.

[Squirt's Mom]

My Squirt used Anipryl with success for about 9 months - much longer than it usually works when it does. For Anipryl to have any effect at all, the pup MUST have the pituitary form of Cushing's (PDH) - Anipryl will do absolutely nothing for the adrenal based form (ADH). In addition, the tumor on the pituitary MUST be in the pars intermedia portion of the pituitary gland. 85% of cush babies have PDH; of that 85%, about 20-25% of those pups will find Anipryl is effective. We were extremely lucky with Anipryl that it worked as well as it did for as long as it did. Squirt was not the typical cush pup. Because of our experience with this drug, I always support it's use tho many don't. In this case with the apparent sensitivity to the Vetoryl (Trilostane) I think trying the Selegiline (Anipryl) is worth a shot. If it works, it will give you a few months to look into other options.

Anipryl does have side effects. It can make them nauseated; keep Pepcid AC (NO OTHER FORM OF PEPCID) on hand as she may need that daily or another antacid approved by the vet. It can make the very restless, especially in the beginning - it is metabolized into something similar to speed in dogs. But this aspect fades with use - digestive upsets do not. I am glad that her blood pressure was checked before starting this drug and recommend it be monitored after starting just in case. BP can spike causing problems yet be normal when checked - the spikes have to be caught. With the nose bleeds, the BP should be monitored anyway I would think to make sure there isn't something going on causing extreme spikes. Here is a link on Anipryl - http://www.drugs.com/vet/anipryl-tablets.html

Unless you are in the UK, you do have another option - Lysodren. Some folk, including some vets, are afraid of this drug. But I am much more afraid of Vetoryl myself and will always choose Lyso first if faced with other cush babes. Lysodren has been around for a very long time and we KNOW what it is doing in the body. Vetoryl is the new kid on the block and we are still learning exactly what all it does and how to use it. BOTH drugs have the exact same warnings, up to and including death. Neither drug is safer than the other. BOTH are life-savers for our babies. It is not uncommon to find that a pup simply cannot handle one or the other and needs to switch. Some can't handle the Trilo, some can't handle the Lyso...but do wonderfully on the other when switched.

Are you a member of our sister site, K9Diabetes? If not, go register. They are THE experts on canine diabetes. http://www.k9diabetes.com/forum/ That does NOT mean you get to leave us, tho - nope, not at all. You and Daphne are family now but we do want you to have the best of both.

Hugs,
Leslie and the gang