Dosage Dilemma - now Muscle Weakness/Atrophy

[jenglishsr]

My vet recently prescribed Trilostane for my 18 lb (due to Cushings) mini-dachshund. I am suspecting that he erred in setting her initial dosage. First of all, he said that the dosage that he would recommend was so small that a pill could not be halved in order to equate to the correct dosage. He therefore had the medication compounded and put in liquid suspension form. The suspension ratio is 2mg/ml. He then goes on to prescribe a dosage of .45 ml twice a day. If my math skills are serving me correctly, this would equate to a twice a day dosage equivalent of .22 mg of Trilostane twice daily. This hardly seems to comport with the minimal recommended twice daily dosage of around 8 mg per day. Since I took Isabella off of the homeopathic medicines she was taking (about a week now) and switched her to my vet's recommended dosage of Trilostane, she has regressed considerably. I suspect that it is due to her actually taking an almost negligible dose of Trilostane for over a week now. Can anybody help me out here?

Thanks,
JE

[labblab]

Hello and welcome to you and your girl! You will see that I have moved your thread to our main "Questions and Discussion" forum -- this way, more people are likely to view it and reply to it. ;)


The suspension ratio is 2mg/ml. He then goes on to prescribe a dosage of .45 ml twice a day. If my math skills are serving me correctly, this would equate to a twice a day dosage equivalent of .22 mg of Trilostane twice daily.

Actually, I think your math is incorrect and that Isabella is receiving nearly 1 mg. of trilostane twice daily, or a 2 mg. daily total (if she gets two .45 ml doses, that would be just shy of one full ml in total). However, you are totally correct in that even 2 mg. is a tiny, tiny amount of the drug and unlikely to have any therapeutic effect. The most widely accepted initial dosing formula worldwide is a daily total of 1 mg. per pound. So at her weight of 18 pounds, she could easily be dosed with two 10 mg. capsules of brandname Vetoryl (either two capsules once daily or one capsule twice daily). If your vet wanted to be even more conservative, Isabella could be started off with only one capsule given once daily.

So the dosing prescribed by your vet is totally puzzling. Do you know if he has much experience with treating Cushing's dogs? Also, it will help us a great deal if you will share more details about Isabella's overall health history, her current symptoms, and also the diagnostic testing that pointed to Cushing's. In the meantime, here's a post on our "Resources" forum that gives more specifics about the most current initial dosing recommendations.

http://www.k9cushings.com/forum/showthread.php?p=1251#post1251

Marianne

[jenglishsr]

A bit more on Isabella, other than her Cushings, she has had some skin allergies in the past. Other than this, she has been a rather spunky; very smart and interactive dog.

The vet caring for her has been practicing for over 30 years; he has seen more than his share of dogs with Cushing. He made a calculation error, in my opinion. When he told me that the smallest pills on the market for Cushings was too small to give an equivalent pill dosage, I was a bit perplexed. I had read a good deal on this and other sites regarding Cushings and I had never saw a post that talked about administering the dosage via an oral suspension.

Again, I appreciate any and all input regarding my dilemma.

JE

[labblab]

I think you will need to contact your vet first thing tomorrow and clarify his dosing intention. It seems as though miscalculation would only be part of the issue since the only reason why you could not give Isabella 10 mg. capsules is if your vet wants to start at a twice daily dose even lower than the formula recommended by Vetoryl's manufacturer. On the face of it, giving an 18-pound dog 20 mg. of medication would have seemed to be pretty straightforward. So you will need to find out what dosing protocol he is wanting to adhere to in addition to the correct calculation.

Throughout time, we have had a few other members who have used liquid suspensions. The advantage is that you can easily manipulate dosages. However, I am not sure whether the drug remains as stable for as long a time as when it is administered in capsule or tablet form. You will want to confirm the shelf life with the pharmacist who compounded the liquid if it is not already listed on the bottle. However, in this situation, you may end up using up the liquid very quickly in order to actually arrive at a therapeutic dose. :o

Just so you'll know, if you opt to continue using a compounded version of the medication, capsules/tablets can be made up in any dosage amount other than the 10, 30, 60, and 120 mg. doses of brandname Vetoryl. So if you prefer not to be measuring out a liquid, you can obtain a custom dose in solid form.

Marianne

[Budsters Mom]

My dog weighed 15.5 - 16 lbs. He was started on 20 mg. compounded Trilostane once per day. His cortisol was controlled well on that dosage. He had other issues, but the problem was not with managing his cortisol. His dosage was compounded in capsule form. He did not require liquid suspension.

I don't understand much of what your vet is doing, but I would seek clarification as soon as possible.

The more you learn. The better advocate you will be for Isabella. Don't assume the vets know proper protocol because they don't always and their mistakes can be life-threatening. I have dealt with this before, so I know firsthand that it happens. It's your job to protect Isabella.

You are off to a good start because you are asking questions. Keep asking.;)

Kathy

[flynnandian]

your liquid suspension is 2mg/ml.
your vet prescriped .45 ml twice a day.
your dogs weight is 18 pounds.
i think your vet meant 4.5 ml twice a day, then it would be 18 mg a day and that is exactly the recommended starting dosage! [1mg/pound or 2 mg kilo]

[labblab]

Wow Iris, thanks so much for working out that calculation! Hopefully that is indeed what the vet envisioned, but if so, for sure the error has got to be clarified with the compounder ASAP.

For what it's worth however, if it were me and that is really the strategy, I would prefer to dose with Vetoryl capsules than with a compounded liquid considering that the dosing discrepancy is so minor (18 vs 20 mg.). The way in which the drug is "delivered" via the brandname drug in capsule form has been researched and established; that is not the same case with a compounded liquid suspension. But I am neither a vet nor a pharmacist, so you can take my opinion with a grain of salt. ;)

Marianne

[lulusmom]

Iris' explanation of 4.5ml is definitely one possibility but it would be somewhat odd to have a client give their dog 4 1/2 syringes of meds. I think a more plausable explanation is that there may be a typo on the bottle and it's not really 2mg/ml but 20mg/ml. If so, .45ml would be 9mg which is spot on for an 18 pound dog. I would recommend you call your vet to confirm.

Glynda

[flynnandian]

yes glynda, i thought about that too. a typo indeed.
JE, can you give us more info on the test numbers of your dachshund?
maybe the regression means that 18 mg is too much for her.
is she still eating, drinking, walking fine? normal stools etc.?

[jenglishsr]

Thanks everyone for your reply. I went to the vet early this morning; unfortunately, the vet is trying to stand by his dosage saying that he got it from an endocrinologist; not stopping to think that he might have gotten this entirely wrong. I am going to a specialist on Wednesday and hoping to get some clarification on this. I am certain that the vet made a mistake and it galls me that he is not open to the idea that he did in fact err. No where on the web, including a manufacturer of Vetoryl, does it call for such a low dosage.

Meanwhile, I put Izzy back on the homeopathic meds that had arrested her symptoms in the first place. I only switched to Trilostane because I felt that she had plateaued with the homeopathic meds (Drenamin, Adrenal Gold and Pituitrophin).

[Budsters Mom]

What kind of specialist are you going to see? Is it and IMS(internal medicine specialist)?

[jenglishsr]

My wife and I have made a decision to stop going to the vet for the treatment of Isabella for Cushings. The Trilostane regimen with the ever present testing and retesting is simply the straw that broke the camel's back; we were looking at about another $2000 in vet bills after spending well over $3,000 thus far. And most likely well over a $100 per month for the Trilostane.

Izzy does well with the homeopathics Adrenal Gold, Pituitrophin, Drenamin and 4 Gentlemen Tea Pills. We can get all of these at our local health foods supermarket and/or online.

Izzy weighs about 18 lbs now (due mostly to the Cortisol). Can anybody help with some tips on dosages. We are presently giving her 1 Drenamin per Day, 1 Pituitrophin twice a day, 1/4 tsp of 4 Gentlemen's Tea (granulated) twice a day and 30mg of Adrenal Gold twice a day. All of the meds are given with meals. We are anxious to hear from other forum participants as we try to treat our 11-year old Dachshund in cost-effective manner.

[Squirt's Mom]

I personally cannot help you with dosages on any of those things. I beg you, if you do not want to follow the traditional way to treat Cushing's, get with an Holistic vet and do not try to wing this yourself. You can easily do much more harm than good.

[labblab]

Just a quick note to let you know I've merged your newest post into your original thread about Izzy. It helps us give you our best feedback when a dog's treatment history is consolidated in one place. ;)

I'm afraid I cannot comment on the homeopathics because I am unfamiliar with their ingredients and/or the manner in which they may interact with one another.

I have to say, though, that I am very sorry that your vet's peculiar dosing protocol did not allow you the chance to see whether an appropriate dose of trilostane would have been helpful to Izzy. That would not alter the expense of testing, but it sure would have been nice to see whether or not she responded positively to the medication. If you do ever decide to return to trilostane, I am willing to bet you could get a 30-day supply of solid compounded capsules or tablets from one of the compounders regularly used by our members here for less than the $100 you are fearing.

Marianne

[jenglishsr]

Thanks for your input. For the record, I have had Isabella on Trilostane and the Homeopathics for two weeks now. However, I cannot get another two weeks approved unless I bring her in for testing. She is very stable and is feeling rather perky and some of her more obvious symptoms (panting and water intake) seem to be abating. I am willing to stay with the 10mg dosage for another month but the vet will have none of it.

[Renee]

She may appear stable, but you really have no idea of her cortisol without that testing. My own pug appeared just fine, but when we tested her cortisol, it was low enough to scare me and we backed off her dosage for a while.

It sounds like you are stopping because you don't agree with your vets protocols for testing? Testing after 2 weeks on a new dosage is standard. These protocols are for her own safety on this drug.

[labblab]

One testing compromise that you might consider discussing with your vet is to check Izzy's resting cortisol alone at the two-week mark, and reserve the full ACTH for the 30-day testing. The resting cortisol is less expensive, and provides some limited information. You cannot make decisions re: increasing a dose using the baseline alone because a higher baseline is subject to too many variables aside from medication dose alone. But you can gain some info as to whether the cortisol is dropping too low, which from a safety standpoint is the chief reason for performing the two-week check, anyway. As long as the resting cortisol is higher than 2.0 ug/dL and the dog is behaving normally, you have some assurance that the cortisol is not being oversuppressed at that time. A few noted clinicians have adopted this interim testing protocol for two-week checks, but of course there are others who prefer that the complete test be done at all times. Your vet might be interested in considering this option, though, especially since Izzy is taking a conservative dose of trilo based upon her weight. Just a thought for you to consider, because it seems a bit of a shame to discontinue the trilo if you are seeing improvement even on this initial dose.

Here are the stated results of a related research study which supports the use of the baseline cortisol in certain decisions re: oversuppression. You'll note that the study had even a lower cut-off than 2.0. But from what I've read, 2.0 seems to be a more commonly accepted threshold.


Results of 103 and 342 ACTH stimulation tests before and during [trilostane] treatment were evaluated. In this population, baseline cortisol concentrations ≥ 1.3 μg/dL accurately excluded excessive suppression (defined by cortisol concentration after ACTH stimulation < 1.5 μg/dL) in 254 of 259 (98%) dogs.

Marianne

[Barb]

I do understand your frustration but I don't think what you have her on now will help with Cushings.
I know selegine is not used much anymore but maybe you could ask your vet if that would help. Our vet at the time put my little doxie on this when she was diagnosed at age 10 and she lived a healthy life of over 16 years. With selegine you don't need as much testing and it is not expensive at all.
I think it may help your dog if it's pituitary cushings.
It's worth a try.

[labblab]

Yes, that's true, Barb's suggestion might also be something to discuss with your vet. Unfortunately, selegiline (brandname "Anapryl") only seems to help a small percentage of dogs -- those who have pituitary tumors located in a specific spot. But if it works, it can indeed help relieve symptoms and as she says, monitoring testing is far less extensive. So that might be another option to consider if you don't want to continue with the trilostane.

Marianne

[Squirt's Mom]

Anipryl helped Squirt for about 9 months in the beginning. But the drug itself DID cost more each month than her Lysodren did; her Selegiline was compounded. However, the testing for Lyso was WAY more expensive than for Anipryl. ;) And Marianne is right - the dog must have PDH (it will do nothing for the adrenal based form) and the tumor must be on the pars intermedia portion of the pituitary gland. About 20-25% of dogs with PDH have the tumor in that spot but this drug is still worth a shot in my mind.

[Barb]

Wow, that price has gone up. I order my meds from Allivet because I found them to be one of the lowest.
They sell Selegiline 5 mg Capsule #60 for $55.99.
Vetoryl 10 mg, 30 & 60mg. Depends on dosage. The 10 mg is $41.99 #30.
Just to give you a comparison.
I'd ask your vet about it and if they can tell you the location of the problem and if this would be an option because the testing was much cheaper as I remember going back to 2002 when my dog was diagnosed.

[Squirt's Mom]

Lysodren, not Vetoryl; Vetoryl is given every day for life, Lysodren is not. Squirt took 2 tablets a month of Lyso. A 3 month supply cost around $70 last time I bought it in 2014. A one month supply of her liquid compounded Selegiline was around $90 in 2008-9.

[Gwenny6]

When I purchased Lysodren it was $200 for 40 tablets of 500mg. That was through Stop and Shop Pharmacy and with a coupon that I found online.

Thanks for the info on Allivet. Clavamox is much cheaper on there!!!

[Squirt's Mom]

yeah I don't use credit cards so I was limited to those who would take PayPal. I got something like 6-8 pills each time but that would do her for a couple of months at least. EDITED TO ADD - she only took 1/4 pill at a time.

[jenglishsr]

Our mini-dachshund, Isabella, has finally had her Trilostane dosage honed-in (15mg - twice daily). Her urination frequency and water intake have returned to near normal levels. We are pleased with these results. However, she has recently began experiencing acute muscle weakness and atrophy well beyond what she used to exhibit when she first began to show Cushing's symptoms. We appreciate the insight and input from forum members with respect to Isabella's dilemma.

[labblab]

Hello and welcome back, although I'm sorry Isabella has sprouted this new issue. You'll see that I've merged your new post into your original thread so that we'll have all her history consolidated in one place.

We do have a few other folks who have battled increasing atrophy even after supposedly therapeutic treatment is in place, and I hope they will be stopping by to talk with you further. But first, I just want to get up-to-date re: Isabella's trilostane dosing history in order to make sure that it's not contributing to the problem. When we first met Isabella, she was taking a tiny amount of liquid trilostane that was likely having no effect at all. When you last wrote to us about a month ago, it sounded as though you had increased her to 10 mg. (once daily?) about two weeks prior to that. But just within this past month she has been given quite a large increase to 15 mg. twice daily (30 mg. total)?

This is quite a big jump in a very short amount of time, and I'm fearful that you may have gone from giving her too little medication to giving her too much. If so, the muscle weakness may be the result of overdosing and a cortisol level that has dropped too low. How long has she been taking the 30 mg. daily total, and when was her last monitoring ACTH test? Can you describe the muscle weakness in greater detail, and are you seeing any other negative changes?

Sorry for so many questions, but your answers will help us in trying to sort things out.

Marianne

[jenglishsr]

Marianne: Thanks for your reply and continuing concern. As for the dosage issue. You have correctly noted that she was started, by mistake, on a dose .45 mg of Trilostane twice daily; less than a full mg. After taking her to a fairly well known Vet Endo specialist in San Diego, she was started on 10mg twice a day. This initial dosage was based upon her original ACTH Simulation Test. After abut 3 weeks, we had another ACTH Simulation Test and her dosage was increased by the specialist to 15mg twice a day. We had a test taken about 2 weeks ago and the specialist indicated that 15mg twice daily was right on target. I have been told to get her tested again "one month later," which will be about 2 weeks from now. Given this background, I am fairly certain that we are administering the correct dosage; however, we will certainly know more in 2 weeks.

I will keep the forum informed as to the results. Thanks again for your help and support.

JE

[jenglishsr]

Marianne: I forgot to describe the type of atrophy/weakness. It is more pronounced in her hind legs. Her hind feet simply do not support her when she attempts to walk. When she is able to walk it is very laboriously and she has no traction (or very little) on our hard wood floors. Her pot belly stomach has increased a bit (after several weeks of trending downward). I hope that this information helps other forum members to join this discussion and help us out.

[My sweet Ginger]

Hi,
We'd really like to know the actual pre and post numbers from last ACTH test and how long she was on this 30mg. Thank you, Song.

[labblab]

Yes, as Song says, we'd really like to know the actual monitoring test numbers. Also, can tell us exactly how long she had been taking the 15 mg. twice daily before this most recent ACTH was performed? The thing is, cortisol levels can continue to lower for several weeks even though a dose is unchanged. So, for instance, if she was tested two weeks after the dosing increase and her cortisol at that time was fine, it is still possible that her cortisol has subsequently dropped even further.

I think you need to call your IMS tomorrow and alert him to this sudden change in Isabella's behavior. Whether or not low cortisol is the culprit, it is a worrisome development and I think he needs to be alerted. Given Isabella's weight, I do think it was reasonable to start her at 10 mg. twice daily, and the increase to 15 mg. twice daily may also have been totally appropriate. So it's not that I am criticizing the dosing decisions up to this point, but I am just wanting you to know that it is possible that Isabella's cortisol may have fallen lower since that last test. That's why it's so important to note any behavioral changes and report them to the vet, so that necessary adjustments can be made sooner rather than later.

I'm not sure we know how old Isabella is, but another possibility is that her cortisol level remains in therapeutic range but the lowering of her cortisol may have unmasked other inflammatory problems, like arthritis, that are now bothering her. My nonCushpup Lab is having a lot of mobility problems right now that are likely stemming from arthritic pain in her hip. She has trouble standing up and maintaining herself on our wood floors, too. But we think pain and stiffness are the primary problems for her, and not necessarily muscle weakness. If Isabella is having similar problems, your IMS may be able to help with pain relief options. So once again, regardless of cause, I think you'd best let him know what is going on.

Marianne

[jenglishsr]

Marianne/Song:

I don't have the pre-post numbers; however, I will check-in with the endocrinologist first thing tomorrow morning. As for her age; she is 11 years old. Since the onset of Cushing's she has ballooned up to 19.4 lbs; this even though I am feeding her a grain-free maintenance diet and keeping the per meal servings down to a minimum. Our other doxie, is slim and trim and he is eating the same amount.

JE