Sarah & Max: Trilo not resolving symptoms [Archive] - Canine Cushing's Information and Support Forums

Sarah&Max

04-05-2010, 10:22 PM

Hi there,

I have no idea if I'm posting this in the right spot, so I apologize if I'm not!

We (me and my husband Adam) adopted Max, our wonderful beagle, in April 2008 from our local humane society. He is now 11 years old, as far as we know.

He's a very sweet, mellow dog--not vocal at all (strange for a beagle!) and is a great, lovable companion. He is VERY low key--pretty disinterested in other animals and doesn't play--he sleeps a WHOLE lot and is really only interested in cuddling, food, bones, and sniffing around outside.

He was diagnosed with Cushings last September--we were out of town and a friend was watching him, and said he was obsessively drinking water (over the year+ we had him, his thirst had increased) and peeing inside the house, which he had never done with us. I'm not sure if
his Cushings is pituitary dependent or not. At the time of diagnosis, our vet suggested that with his age and his other "health" problems (crutiate injuries that he healed without surgery through rest and activity restriction), we should try the generic of
Anipryl first.

He's been on this since then (on the name brand now, because the generic isn't being made anymore? anyone who has info on this--please let me know!), and has increased to 30 mg a day. It *has* definitely helped him. His coat is beautiful and shiny now, he has less accidents, is less sleepy all the time, etc. He still has a real big appetite and drinks a lot of water, though it's really hard to tell how different that is, because now we restrict it (he gets 2 liters per day now, so we aren't being unreasonable or anything). He was having about 2 accidents a month up until recently. In the past week, he's had a handful, so I took a urine sample in and it turns out he has a UTI, so the antibiotics will hopefully clear that up and help with the accidents. His back legs are still pretty weak (we didn't realize the cruciate injuries were probably the result of the Cushings because they happened before he was diagnosed) but now we just know that he can't attempt to jump on the bed, etc.

I am having a hard time, though, trying to decide if I should keep him on this, or if we should try Trilostane. I would say the Anipryl has improved the quality of life he would have had if we had done nothing, but it's hard to think that maybe there's something better out there too. The extra money for testing isn't the main concern I have--I just don't want to run the risk of putting him through something that could make him really sick, when he lives a pretty good life right now.

I can tell you for sure that I can't answer any questions about testing/levels/etc. because on Anipryl, you don't have to test them. I know that he does not have diabetes, and when they did bloodwork when he was first diagnosed, everything looked fine (kidneys functioned normally, etc.)...

It seems as if the people in this group are really knowledgeable, so I'd love to hear what you think. However, I can also tell you that I'm not the type who is going to go out and see a specialist and drop thousands of dollars. We adopted Max at 9 years old to give him the best life we could--he would have been put down if we hadn't taken him in. So far, I think we've done a great job of giving him a final chance at a good life (he was adopted twice before us!) I just wanted to be forthcoming about that.

Max is my first dog--I grew up with a VERY allergic/asthmatic brother, so this is my first experience with a serious medical problem in an animal. I love him so much... I really want to be doing the right thing!

Thanks again for reading,

Sarah

StarDeb55

04-05-2010, 10:42 PM

Sarah, I would like to welcome both you & Max to our group. We will be asking you a lot of questions, but that simply helps us to give you the best feedback we can from the group's collective experience.

First of all, it's good to hear that anipryl has helped to alleviate some of Max's symptoms. The down side to anipryl is it's only effective in about 15-20% of dogs who have a lesion in a specific location in the pituitary gland, the pars intermedia. I'm a little confused here as to how the Cushing's diagnosis was reached. Were any Cushing's specific diagnostic tests done such as an ACTH or low dose dexamethasone suppression? Was the diagnosis simply made based on Max's symptoms & general bloodwork such as a chemistry panel? Even though you don't have copies of Max's labwork, could you give a little more detail on what was done to get a Cushing's diagnosis?

The goal of treatment is stop the adrenals from the overproduction of cortisol which is what does the long term damage to a pup's internal organs. There really are only 2 effective drugs that will do that lysodren & trilostane. I know it's very hard to make a decision about treating a senior pup. I was faced with the same decision when my Shih Tzu, Harley, was diagnosed 2 years ago at the age of 13. He is 15, now, has been on lysodren for 2 years, & is doing well.

because now we restrict it (he gets 2 liters per day now, so we aren't being unreasonable or anything).

I must comment on this statement. It is extremely dangerous to restrict/limit water for a Cushpup. They are not peeing buckets because they are drinking gallons. It is quite the opposite, their kidneys are working overtime leading to excessive urination, & the pup must drink an adequate amount of water because of this or they can dehydrate very quickly, & get very sick, very fast. Please do not restrict the amount of water that Max can drink. This is a recipe for disaster.

We are here to help you & support both you & Max in any way we can. Looking forward to hearing more.

Debbie

frijole

04-05-2010, 11:10 PM

Sarah,

I can't offer much in terms of advice re anipryl because I use lysodren. We don't see it used a great deal anymore. In terms of "old age" my dog was 12 1/2 when diagnosed and she is now 16 and 3 months!!! I can thank lysodren for that. And the people here.

I ended up using lysodren because my vet was familiar with it and back then trilostane was pretty new. Over the years I'd guess its about 50/50 now. Trilo/lysodren users.

Obviously trilo appears easier to administer etc. but in some cases, over time owners have had to switch from trilo to lysodren due to an increase in sex hormones caused by the trilo. That is the short version.

Please tell us more about the diagnosis and Max's tale so we can best help you. Glad you found us!! Kim

marie adams

04-06-2010, 01:23 AM

Hi Sarah and Max,

Welcome....

I am fairly new to Cushings myself--Maddie was diagnosed in February. I had noticed changes, but thought she was getting old--11 yrs last Dec. At least that is what the vet kept telling us. I finally found a site that link to Cushings and I knew that is what she had because all her symptoms were there to review.

Anyway, I treat with Lysodren. It scared me to death to put her on this drug, but everyone here has been so supportive and helped me along the way. I am in the process of changing vets because the last one--not so much help with the whole situation. If not for all the GREAT advice I have received here I would be totally nuts.

I too do not want to make someone's yacht payment, but get the best help I can for Maddie. I want a partnership with a vet, one that will listen not yell at me, and understand me questioning them if I do not agree. :D

Since she has started her treatment the ravenous eating has stopped, the panting, water comsumption, etc. has decreased so I feel this is good. We are working on the energy level and getting back her hind leg strength. So this drug has been very helpful to getting back quality of life. At some point her fur will grow back in the bald spots.

Good luck with everything and remember you are not alone in this adventure. :)

Sarah&Max

04-06-2010, 11:29 AM

Thanks for all of the feedback already!

The doctor did do an ACTH stim test to determine it was Cushings. That was back at the end of August/early Sept. He hasn't had any tests since then.

In terms of the water "restriction"--I should have said monitor rather than restrict. We give him as much as he wants, which ends up being about 2 liters per day, we just give it to him when he goes into the kitchen to look for it, rather than leaving the bowl out. If we left the bowl out, he'd pee all over the house all day long. I know how to check for dehydration (gums, etc.) and I've been doing this for 8 months now, so I feel confident that I'm not doing anything terrible.

I've gotten two separate opinions bout Max's condition... neither vet seemed to think that it was imperative that we try the Lysodren or Trilostane right away. I belong to another Cushings group online and a lot of people on there have had bad luck with Lysodren. I just don't feel comfortable using it at this point. Maybe my mind will change at some point.

Anyhow... thanks for your quick responses!... I know I don't have a lot of answers, but I did want to reply about the water consumption and how his diagnosis was determined.

Sarah

Casey's Mom

04-06-2010, 11:32 AM

Hi Sarah and Max,

Welcome to our group!! My dog is on Lysodren and doing very well - thanks to the amazing people on this forum who have held my hand and answered all my questions and luckily thanks to my vet for a fast, correct diagnosis.

My vet did a UC:CR test first to rule out cushings - which it did not:(, then an ACTH test to determine if she had cushings. There are other tests you can have done - low dose dexamethasone test and an abdominal ultrasound and plenty of members here who can advise you which tests you should have done.

Please do not restrict water as mentioned previously. This can be very harmful to your pup and as explained it is because they have to pee so much that they have to drink so much and not the other way around.

Hugs to you,

Sarah&Max

04-07-2010, 03:59 PM

acushdogsmom

04-07-2010, 04:18 PM

I have been thinking a lot about possibly having Max switch to Trilostane. I remember hearing something recently about a study out of the University of California (Berkeley) that determined that dosing should be lower than what vets had previously thought. Does anyone know of the article I'm thinking of and/or where I could find it? Thanks,

SarahI think the article you're looking for may be the one which is referenced here:
http://www.k9cushings.com/forum/showthread.php?t=185

direct link to the dvm360 article:
http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=460965&sk=&date=&pageID=1

On page three of that article, it says:

In the United Kingdom, trilostane is officially registered for use in dogs under the trade name Vetoryl. The product for use in humans is listed as Modrenal. The current recommended initial dose is 30 mg once daily for dogs that weigh 3 to 10 kg; 60 mg once daily for dogs weighing 10 to 19 kg; 120 mg for dogs that weigh 20 to 40 kg, and 120 to 240 mg for dogs weighing more than 40 kg.

Re-evaluations are suggested after one, three, six and 13 weeks, and then after six and 12 months. Each re-check should include a history, physical examination and an ACTH stimulation test. The ACTH stimulation test should be completed two to six hours after administration of the trilostane. The target range for serum or plasma cortisol concentration should be between 1 and 2 mcg/dl.

It is readily apparent that these dose recommendations result in tremendous dose disparity among dogs. A dog that weighs 3 kg, being given 30 mg once daily, receives 10 mg/kg, while a dog that weighs 20 kg receiving 120 mg would receive 6 mg/kg. A dog that weighs 40 kg could receive as little as 3 mg/kg. These dose disparities can result in severe negative side effects.

Experience at UC-Davis differs quite a bit from that in the literature and the United Kingdom.

The UC-Davis current recommendation is to initiate trilostane therapy at 1 mg/kg once daily. That dose is continued for about one week until a veterinary re-check can be completed.

Owners are instructed to collect a small urine sample from their dog before leaving home the morning of the scheduled re-check prior to trilostane administration. Trilostane should then be given and the dog should be seen by the veterinarian two to three hours later.

The goal of therapy is an owner who is completely pleased with the response. As aids in achieving this goal, both urine and blood tests are indicated. The urine should be checked, at a minimum, for specific gravity, glucose and urine cortisol-to-creatinine ratio (UCCR). An ACTH stimulation test should be started at the time the dog is seen, again about two to three hours after trilostane administration.

The UCCR result should be within the reference interval and the post-ACTH serum cortisol concentration should be between 1.5 and 5.5 mcg/dl.

If the serum-cortisol concentration is within that goal and the UCCR is abnormal, the medication should be given BID. If the serum-cortisol concentration is too high, the trilostane dose should be increased. But if the serum-cortisol concentration is too low, the dose should be decreased.

This approach should be used at each re-check until the dog is doing well.

Sarah&Max

04-07-2010, 04:47 PM

Thank you so much for your quick response! That's exactly what I was thinking of!

jrepac

04-07-2010, 10:51 PM

I have been thinking a lot about possibly having Max switch to Trilostane. I remember hearing something recently about a study out of the University of California (Berkeley) that determined that dosing should be lower than what vets had previously thought. Does anyone know of the article I'm thinking of and/or where I could find it? Thanks,

Sarah

you may want to look into trilo as an alternative, if you feel there is benefit above and beyond the anipryl. I'm still using generic anipryl for my Aussie terrier Mandy (18 months now) and have been very happy w/the results. I saw a big reduction in the cushings caused behaviors (peeing all over, wanting to eat at all hours, restlessness, etc.). Plus some good improvement in skin, coat and tummy (less sag). But, it is hard to get to 100% perfect; not sure it is possible. Unfortunately, some dogs respond to the drug and some do not. If the time comes to switch from anipryl (if it is no longer working), I would lean towards trilo as well, but everyone has a different point of view on this. If you are still getting good response w/anipryl and the other symptoms are manageable/tolerable, you may not want to switch off. It is a tough call to make.

For UTIs, you may want to add some sort of urine acidifier to the regimen....there are several you can buy from catalogs or online.....cranberry supplements work, I have learned. I have not seen a UTI in the nearly 2 years since I started giving cranberry supplements; if you go w/the tabs, look for lower concentrations 185 -250mg per tab/cap, not the super concentrates. Also, L-Glutamine,either daily or a few times a week can help w/muscle tone (or muscle wasting, if that is occurring). start w/500mg caps or tabs. A few of us are using those.

The main generic supplier of selegiline (a.k.a. Anipryl) in the US--was Apotex; and they recently stopped making it! Big headache! There is another generic company called Dava that produces it in capsule form. you can get it at Walmart...I paid $118 for 180 5mg capsules (which is a 3 month supply for me)...still lots cheaper than brand name Anipryl at $80 a month. Apotex was only $75 for a 3 month supply which was a very good price from 1-800-pet meds. Also, Diamondback Drugs will compound selegiline capsules for you in the needed concentration; just email them. As I recall, their price was also excellent.

Good Luck to you

Jeff & Mandy

Sarah&Max

04-19-2010, 10:35 AM

Hi, I just wanted to update about what's going on with my dog now.

I took Max to the vet on Wednesday and after talking to the vet for a long time, we decided to start him on Trilostane. He started on Friday, just 20 mg. in the morning (he weighs 38 lbs.) because I wanted to start low (after reading the UC Davis recommendations.)

He seems pretty normal so far, the only weird thing that happened, which I sort of wanted some feedback from all of you about, is that very early this morning, he threw up a tiny bit. He has done that before--it seems almost like he will do it when he's really hungry in the morning (every other time he's done it, it's been in the morning.) After that, he went back to sleep, and then was back to normal when it was time to eat breakfast. I wasn't sure if I should give him his dose of Trilo after that, but decided that since he was acting normal and definitely had his appetite, that I'd give it to him. It was too early to call the vet.

Once the vet opened and I was able to call, she told me to withhold the Trilo tomorrow if he throws up again today. Does that sound right?

Any advice would be great--I'm a little worried. Thanks!

Sarah

Squirt's Mom

04-19-2010, 11:42 AM

Hi Sarah,

First, a belated welcome to you and Max!

It's kinda a motto around here that anytime a pup is sick for any reason, don't give the med - Trilo or Lyso. So, your vet is right...don't give the Trilo tomorrow if Max is sick again any time today or tonite, and call her asap. That advice will hold true for diarrhea, lethargy or weakness as well. Did your vet give you any prednisone?

Keep your chin up! You are doing a great job!

Hugs,
Leslie and the girls - always

Sarah&Max

04-19-2010, 04:57 PM

Thanks so much for your quick response! She did give me Prednisone. So far, it seems like it must have just been a fluke. He's eating at acting totally normal, but I'm going to keep my eyes peeled for anything else that seems odd.

Sarah

zoesmom

04-19-2010, 06:39 PM

Hi Sarah -

I'm hoping that the barfing was just a fluke too. My daughter had a small dog who did that . . . if she got overly hungry (threw up in the early am - usually just bile. She was better if fed twice a day.) So that only brings one quick question to mind. Are you feeding Max when you give him his pills. Sounds like you're giving the trilo in the a.m. only? When my Zo started on trilo, she only ate once a day - in the evening - and so I had to switch her to twice a day feeding, since she got took her trilo in the a.m. at first. Also, just make sure you give the pill AFTER they eat, 'cause sometimes they'll pull a fast one and decide not to eat, right after you give them the pill. Just keep a very close eye on Max over the next few days for anything that seems 'not right'. We had trouble on the third day, but Zo was NOT started on a very conservative dose. Sue

PS - Also, wondering if they did an ACTH after stopping the anipryl and right before starting the trilo? As a way to measure Max's progress, it's good to know where he was starting from with cortisol levels.

Harley PoMMom

04-19-2010, 07:14 PM

Some of us give our pups Pepcid AC 20-30 minutes before they get their cushings meds/meal. Maybe ask your vet about using this...just a thought. ;):)

Love and hugs,
Lori

jrepac

04-19-2010, 07:21 PM

I always give the am pills with a morning meal; pm pills with a snack of some sort as well....even if it is a piece of turkey, ham, cheese or even a dog biscuit

but, if the vomiting keeps up, please hold off on the meds and call your vet!

Sarah&Max

04-19-2010, 09:08 PM

Thanks everyone! I do feed Max twice a day, and we give the pills after he eats. I'm keeping a very close eye on him... so far he's been acting pretty normal. In fact, he actually wanted to go on a walk today, which he has not done in months! I was so excited I wanted to cry! We took it easy and just went down to the end of the street and back, but I was so happy to see him interested in sniffing around and checking things out. I am really hopeful.

The only other weird thing I've noticed is that he's trembled a couple of times, but it's hard to tell if anything is causing that because he does that normally if he gets startled or is cold, or thinks that we are about to leave for work. Other times he seems to do it for no reason at all. Should I be worried about this?

Thanks for the suggestion about the pepcid--I'll ask my vet on Friday.

They did not do a stim test last week--I think she was probably trying to keep my costs low.

Anyway, thanks to everyone for responding! I'll keep you all updated.

Sarah

Harley PoMMom

04-19-2010, 09:22 PM

Trembling can be a side effect of the Trilostane.

I would of gotten a stim test done, just a post draw, so you could have something to compare to next time and to see exactly where you are now...JMO ;):)

So glad Max was feeling much better and that he took you for a walk! :p:D At least that's what my boys do...they take me for a walk! :eek::)

Love and hugs,
Lori

Sarah&Max

04-19-2010, 09:59 PM

Thanks, Lori. I didn't even think of the stim to be honest... it's just been such a crazy few weeks, and I wasn't thinking of it since there's no testing necessary with Anipryl.

Is trembling something I should be worried about, or just a side effect?

zoesmom

04-19-2010, 10:15 PM

I think the trembling may be just a side effect of the drug. We've seen a number of dogs on trilo who've had it. Zoe did it, not right at the beginning, but a couple weeks into tx. It was actually more like shivering and mainly across the back of her neck. I've never heard anything about it being a concern. If it's a passing thing, probably not to worry. Sue

Sarah&Max

06-21-2010, 10:22 PM

I know it's been a long while since I posted last, and a lot has happened since I last posted but I need some advice!

My dog Max switched from Anipryl to Trilostane shortly after I first posted. He started at 20 mg, moved to 30 after the first stim test, then to 40 after the second, and now he's at 60 after the third. He's 38 lbs. So far until just today he's been really tolerant of the medication, and today is also the first day that I've seen a reduction in his cushings symptoms (mainly excessive drinking and peeing, and having accidents). This morning he had completely normal poop, but then this evening when I took him out, he had a small amount of water diarrhea. When my husband took him out a few hours later, he had another small burst of watery diarrhea.

He's also currently being treated for a UTI, but he's been on these antibiotics for about 9 days now with no side effects.

He's still really interested in food, but more lethargic than normal and his back legs are a bit shakier than normal, and is not very interested in his bones.

I wasn't able to catch the vet before she left for the day because this happened later, so I thought I'd try checking on here for advice.

We do have emergency prednisone, but I'm not sure if his two small bouts of diarrhea warrant giving it to him. He hasn't had any vomiting. Should I just wait until the morning to hear back from the vet, skip his next dose of trilo, give him the prednisone?

It is so hard to figure out what is a serious symptom or not with this disease and these drugs. Any advice would be helpful.

Unfortunately I don't have any of the stim test numbers, which I know people on here often ask for. When I spoke to the vet on Friday, when we decided to increase to 60 mg, she said that after his most recent test, the first number was perfect, but the subsequent numbers were still high.

Also, does this mean that switching to twice a day dosing might be a better idea? I think I read that somewhere.

Anyway, thanks so much in advance for any advice!

Sarah

AlisonandMia

06-21-2010, 10:43 PM

How many hours ago did he have his trilostane? How many hours was that before the first bit of diarrhea. How many days has he been on the 60mg dose.

It could be the antibiotic - sometimes it takes a while for antibiotics to cause diarrhea because it can be caused by the antibiotic's effect on the intestinal flora rather than being a reaction to the antibiotic itself. It can take a while for the intestinal flora to be affected enough to cause problems.

Do you have the actual numbers from his last stim test?

Alison

Roxee's Dad

06-21-2010, 10:45 PM

Hi Sarah,
The only advice I can offer is to stop the Trilo until Max sees a vet. Kind of a rule of thumb around here. Don't give trilo or Lyso to an unwell pup.

Is he eating his food and drinking water? Would love to see his latest stim results. Normally the first number doesn't mean much, it's the 2nd number after the injection that is significant. Hope you can post them soon.

Sarah&Max

06-21-2010, 11:13 PM

Thanks for the quick replies!

He had his medicine this morning around 7:30 a.m. (EST) and the diarrhea didn't happen until around 6:30 p.m. He's been on 60 mg of Trilostane for 3 days, including today, and takes it all at once. Before that, he was on 20 mg. for about 10 days, 30 for about three or four weeks, and then 40 mg. for about 10 days, until this recent increase.

He's still eating and drinking normally--drinking less than usual, which at first seemed like a great sign, because he's been drinking excessively for about a year now!

I'll be sure to ask the vet for the actual numbers when I speak with her in the morning and withhold the medication until she tells me otherwise.

Thanks again for all of your help.

Sarah&Max

07-09-2010, 01:47 PM

Hi all,

Max is still drinking a lot and peeing a lot on 60 mg of Trilo, and my vet said his stim results were still not in the normal zone (I didn't ask for numbers), so we are going to try 60 in the a.m. and 60 more in the p.m. He's 38 lbs., so he's right on the edge of being in the 120 mg starting dosage range according to Dechra. Is anyone else out there giving a pretty high dosage?

It's worth noting that he's had absolutely no negative side effects from the 60 mg. I had posted last week or the week before about him having really bad diarrhea--turns out he had eaten half a sewing tape measure! After eliminating it, he was fine.

Anyway... I'm a little worried about increasing his dosage so drastically... anyone have any thoughts?

Thanks,

Sarah

Moderator's Note: Sarah, I have merged you new post concerning increasing Max's trilo dose into Max's original thread. We normally like to keep all post on a a pup in a single thread as it makes it easier for other members to refer back to Max's history. I have also modified the thread title to try to reflect your concerns about unresolved symptoms. If you would like a different title, please feel free to PM me or one of the other administrative staff & we will be happy to do that for you.

frijole

07-09-2010, 02:00 PM

Hi Sarah. We can't really give advice if we don't have the whole picture, namely the test results. Please call the vet and ask someone at the desk to open the file and read you the two numbers on the last acth test. Then post them and we can better answer your question.

Many have to tweak trilo dosages but you only do it depending on the test results. Thanks!! And don't feel like you are being a bother to the vet's office- you paid for that test and you deserve/own the number!

:D Thanks, Kim

Sarah&Max

07-09-2010, 02:54 PM

Thanks, Kim. I just stopped by the vet and they gave me copies of his latest test. His pre level was 1.1, post was 11. His urine/creatine test was 110! Hope these numbers help!

Sarah&Max

07-09-2010, 03:06 PM

creatinine, that is!

StarDeb55

07-09-2010, 03:20 PM

Sarah, the post number is very high. Dechra states that the post can be up to 9.4 as long as the pup is clinically well. The ideal range with trilo is 1.45-5.4, if memory serves. I, too, am concerned by the huge jump in dosage. IMO, it would make more sense to probably bump the 60 mg. up to say 90 mg., & see what happens. I think it's a little too soon to jump to twice daily dosing, but if your vet insists, IMO, it would be better to do the 60->30 mg. for 90 mg. total, rather than jump way up to 120 mg. I just want to double check one thing to make sure I understand. On 60 mg., have you seen any improvement at all in any of Max's symptoms?

Debbie

PS- I have also PM'd Marianne about Max as I would like for her to take a look at this since she has had much more trilo experience than I have, along with contacting the Dechra vet staff, personally, with questions.

labblab

07-09-2010, 04:28 PM

Hi Sarah,

Debbie is being very kind in crediting me with trilo experience as I am surely far from being any expert :o. However, I've gotta say that I pretty much "second" Deb's comments ;). All I'm able to do is to cite the published recommendations of Dechra and UC Davis, but they both agree that a switch to twice-daily dosing doesn't really enter the picture until a dog's cortisol level has been lowered to the therapeutic range on the ACTH test and symptoms have resolved for at least the early part of the day. Once that has happened, if symptoms rebound later in the day and a UCCR sample from the subsequent morning demonstrates significant elevation again -- then you can conclude that the effectiveness of the trilo is too short-lived and a second dose is needed to carry the dog throughout a 24-hour period. But even at that point, the dose is not doubled; merely increased incrementally and divided into two.

Here's the relevant quote from Dechra's U.S. Product Insert (http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf):

ACTH result greater than 9.1: increase initial dose.

Once daily administration is recommended. However, if clinical signs are not controlled for the full day, twice daily dosing may be needed. To switch from once daily to twice daily dosing, increase the total daily dose by 1/3 to 1/2 and divide the total amount into two doses given 12 hours apart.

And here's the relevant quote from UC Davis (http://www.k9cushings.com/forum/showthread.php?t=185)(they prefer even a lower ACTH result):

The UCCR result should be within the reference interval and the post-ACTH serum cortisol concentration should be between 1.5 and 5.5 mcg/dl.

If the serum-cortisol concentration is within that goal and the UCCR is abnormal, the medication should be given BID [twice a day]. If the serum-cortisol concentration is too high, the trilostane dose should be increased. But if the serum-cortisol concentration is too low, the dose should be decreased.

The thing is, until a therapeutic ACTH level has been reached on a once-daily dose, an elevated UCCR really isn't telling you anything that you don't already know -- that the dog's cortisol level isn't yet being properly controlled at ANY time of the day. Now of course your vet knows the specifics of Max's situation, and we are not vets ourselves. And it would also help us a lot if you could possibly get the results of all of his previous ACTH tests so that we could have a better clue as to how his cortisol has lowered with the increases thus far. But unless his cortisol has not come down much at all since beginning treatment, if Max were my dog, I'd feel a lot more comfortable increasing his once-daily dose to 90 mg. before doubling his daily dose by adding a second 60 mg. capsule in the evening.

Marianne

Sarah&Max

07-09-2010, 07:48 PM

thank you so much for your thoughtful and knowledgeable responses!

to give you more info: Max has improved on the drug, only in that he's a little spunkier than he used to be, but his water consumption really hasn't decreased at all, and he's still having lots and lots of accidents.

he DEFINITELY gets worse as the day progresses--meaning he has more accidents later at night, but doesn't really have too many problems during the day.

My vet said today his post levels have never been very good, and have varied between 13 and 11. He tested once at 7, I think when he was at 40 mg., but then it's gone right back up since then. We started him very low--at 20 mg.-- based on the UC Davis recommendations. He's been on Trilostane for at least three months now, increasing from 20 to 30 to 40 to 60... with no real change in symptoms, except that he is DEFINITELY more energetic and has more strength in his back legs.

If I add another 30, should I add that at night, or give it all at once do you think?

I am really at a loss here. I don't know what to do! Thanks again for your help,

Sarah

StarDeb55

07-09-2010, 07:57 PM

Sarah, per the Dechra recommendations that Marianne posted earlier, it seems to be way too soon to go to twice daily dosing. The recommendations are that once the ACTH is within range, but there are still unresolved symptoms, especially in the evening, you go to twice daily dosing. If Max were my boy, I would stick with once daily dosing & take it up to 90 mg. Please remember, as I'm sure you know, that a dosage change will need a stim in 7-10 days.

Debbie

Sarah&Max

07-09-2010, 09:17 PM

Thanks again for all of the really useful feedback.

Can I ask what the harm would be in going to twice daily dosing before knowing what the correct dosage is?

I feel very torn here, as I want to do what my vet is recommending but of course don't want to make him sick. She seems very comfortable doubling the dosage for now, but I know that is mainly because he is not showing improvement and seems to tolerate the drug so well.

I feel so confused!

frijole

07-09-2010, 09:32 PM

Sarah, I feel your pain. I have been down the road you are on relative to what to do with a vet and it is tough. You want to trust, you want to obey, it is how we were raised.

Not all vets have alot of experience in treating cushings. Noone understands how tough treatment decisions are more than the dog owner. We are our dogs' voices in all of this. And we aren't vets! So all you can do is read, listen, ask question and go with your gut.

I have never used trilo but I have been active on this board for 4 years - since when trilo was first introduced. What I can share as an observer and reader of other's experiences is that there is a fair amount of dispute as to what the proper dosing amount is. The manufacturer has changed their recommendations. I have to believe there is a reason for it. So no matter how smart my vet is I would at least print out the recommended dosing and ask why he/she isn't following their advice.

Lastly - vets sometimes think that trilo is an "easy" drug and that there are few cases of overdosing. Well - we have seen enough cases where it happens to know that it can happen. With trilo it is much easier and safer to start low and increase slowly than run the risk of overdoing it.

Hang in there and I hope I have helped a bit. Kim

Sarah&Max

07-09-2010, 11:17 PM

Thanks again... I want to be clear about my vet. She is the first to admit that she has only treated a handful of dogs with Cushings, and Max is the first she's treated with Trilostane. She's also really sharp and very willing to read anything I find that seems important or listen to anything I share with her that I find out here or elsewhere online. She had originally said maybe we should try jumping from 60 to 80, and then I let her know that I had seen somewhere on the Dechra website that said that many dogs they had studied ended up with an effective dose that was around 6 mg/kg, which would put max around 100 mg.

She isn't being pushy about any of this... Since we've been increasing his dosage for so long without any result (because we started out being very conservative), I think she's feeling bad that we have already spent so much on the testing (over 1K, which *is* a lot of money for us) and she's trying to prevent that from happening again and again.

I am going to call her tomorrow and suggest we try 90 rather than 120 and see if she still wants me to split it up.

I get the feeling that she is uncomfortable giving him so much all at once, which is why she suggested splitting it up (that, combined with the fact that he gets progressively worse as the day goes on).

Thanks again to everyone for their help with this.

If anyone else has more to share, I'd be happy to hear!

labblab

07-10-2010, 07:50 AM

Can I ask what the harm would be in going to twice daily dosing before knowing what the correct dosage is?

Sarah, first off, I'm glad that you always discuss any dosage changes with your vet, because we are not qualified to tell you to alter a prescription without your vet's input. But since you are asking our thoughts, here's a few more from me. :)

It's not so much that there is any "harm" in going to twice daily dosing. But unless your dog really needs to make the shift, it seems to me that you are complicating your daily schedule unnecessarily by adding the evening dose. It takes some doing to consistently give the doses as close to 12 hours apart as possible, and trilostane is always most effective when given along with a meal. Plus, one of our members who is a veterinary endocrinologist has warned us that dogs being dosed twice daily run a greater risk of dropping their cortisol levels too low, and therefore have to be monitored even more closely.

I think these may be reasons why both Dechra and UC Davis recommend once daily dosing unless effective control cannot be maintained throughout a 24-hour period. If your vet would like some direct feedback from Dechra, I'm certain that one of their technical reps (who are also vets) would be happy to speak with her. Here's contact info for Dechra's U.S. office in Kansas:

http://www.dechra-us.com/Default.aspx?ID=365

One cautionary note...if you are currently using a compounded version of trilostane, Dechra will undoubtedly encourage you to shift to their brandname product, Vetoryl. Whether or not you do so will be up to you and your vet. However, I myself am scratching my head a bit at your report of Max's ACTH results -- you say that they remained consistantly high at the 20 and 30 mg. doses, dropped down to 7 on the 40 mg. dose, and the latest test is back up where it was on the earliest low doses? Did all of these doses come from the same source? These rather odd results do make me wonder whether there could be a problem with the consistency/effectiveness of the medication itself.

So if you've been using a compounded version so far, you may want to bite the bullet from a cost standpoint, and try a course of brandname Vetoryl in order to see whether Max's ACTH results improve. Vetoryl comes in four dosage strengths, but if you buy a box of 60 mg. capsules and a box of 30 mg. capsules, you'd have a fair amount of dosing flexibility within the range that you're currently considering. You can check the internet for the most competitive pricing among web pharmacies and purchase online with an Rx from your vet. You might try starting Max on the 60 mg. capsules for a week or so to see if you notice any improvement in his symptoms. And if not, go ahead and bump him up to 90 mg. once daily. And if you're already using Vetoryl, then you can just ignore these last two paragraphs altogether!

Marianne

Sarah&Max

07-10-2010, 10:28 AM

Thanks, Marianne! Just to answer your question--he does take the name brand drug, so the vet was pretty confused about why his cortisol levels dropped that one time.

At this point, it's just my impression that Max needs a higher dose for it to be effective, so we didn't really need to start so conservatively. Regardless, I'm glad we have been safe about it, but it's hard--it's such an expensive disease to treat. Max is a rescue dog--we adopted him two years ago because he was old and sweet and I wanted to give him the best home he's ever had for his last few years, so I'm trying my best to do that. He just might have to get a part-time job. ;)

littleone1

07-10-2010, 12:10 PM

Hi Sarah,

Corky and I would also like to welcome you and Max. I know how frightening this can be.

Corky is taking Trilostane, and anytime his dosage had to be increased the dosage was no more than a 6mg increase. Corky started taking 20mg once daily. It then went to 25mg once daily, and now he is taking 31mg, but it has been split into dosing twice daily.

I know you have gotten some good feedback from others. I myself would be very hesitant about doubling the dose. You can always get different doses of Trilo compounded that would accomodate a twice daily dosing.

I hope everything goes well with Max's treatment.

Sarah&Max

07-22-2010, 12:45 PM

Hi everyone,

I took the suggestions from everyone on here and we decided to add 30 extra mg, instead of the 60, at night. I just got Max's test results and they were 2.3 pre and 12.8 post, which means it's INCREASED with the addition of more medication. Does anyone have any idea of why this would be happening? We are going to add another 30 mg. to make it 60 in the a.m. and 60 in the p.m., but I have no idea why this is happening.

With the addition of the 30 at night, it has DEFINITELY affected his symptoms. He went all week last week without an accident. He's had a few since then, but his water consumption has gone down quite a bit, and he almost always has the accidents at night. He also has more energy, and is more daredevilish--he's trying to jump on things he hasn't tried to jump on in a year or so, like the bed! So his hind legs must be feeling better.

Does anyone have any idea of why his numbers would be so unresponsive, even though he seems to be improving? I know cortisol is a stress hormone and we have had very bad storms this summer--one of which happened the night before his test. He's terrified of thunderstorms. Could that stress be affecting his numbers?

Thanks in advance for any suggestions!

Sarah

frijole

07-22-2010, 02:06 PM

Sarah, A number of things could explain it... First off - the test could have been flawed (it happens). If not the test then you look at the dog - is there anything at all going on with Max right now? Example - stomach aches, any physical pain or other illness? Non adrenal illness can cause an increase in cortisol. That is why it is easier to commence treatment with a totally healthy dog. Is the drug from the same supplier? Does it look the same or was it color coded as a different dosage amount?

How long were at the higher dose prior to testing?

I would let the symptoms drive my decisions and right now if Max is healthier I would assume the cortisol really is lower. I know that is weird but everything you said suggests that the increase worked... just the test didn't show it.

Interesting.

Sarah&Max

07-22-2010, 02:38 PM

Hi, thanks so much for responding.

Max seems perfectly healthy beyond this--no pain or stomach problems (he still has a crazy appetite). He has no other illnesses that we know of and was tested for diabetes and kidney disease when we first started noticing his Cushings symptoms. We have gotten the drug (name brand) from the same supplier the entire time. He was at the higher dosage for 10 or 11 days before testing.

We are going to increase to 60 a.m./60 p.m. and see if that resolves the remaining accident issues. I just cannot figure out why his numbers aren't changing!

lulusmom

07-22-2010, 03:32 PM

Hi Sarah,

I went back through your thread in order to understand what has taken place up to this point and jotted down some notes which I will share with other members below:

Max weighs 38 lbs
Started treatment at 20mg Trilostane for 10 days, then increased to 30mg after first stim, After three or four weeks, increased to 40mg. Ten days later, increased to 60mg.

Per July 9 post, stim test was pre 1.1 and post 11 and UC:CR 110. Because post still high and Max is still drinking and peeing a lot, switched him to twice daily dosing and added 30mg in pm.

The once daily dose of 60mg is not effective so I agree with Debbie's earlier post that rather than going to twice daily dosing at this point, it would have made more sense to follow protocol and increase the once daily dose. The fact that Max' symptoms have improved with twice daily dosing, despite the latest post stim being 12 ug/dl, is not that perplexing to me. Hopefully I can explain without confusing you or anyone else.

Hypothetically, let's say that before Max's first pill in the morning, his post stim is 20 ug/dl. You give him his morning pill and four to six hours later, when Trilostane is at it's peak, the post stim is 11 ug/dl, which is well above the acceptable range of 1.5 - 9 ug/dl. Now all dogs are different but we know that Trilostane has a short half life and it's enzyme blocking abilities start to diminish any time after 8 hours. So let's speed up the clock and it is now 10 hours after the morning dose and Max' post stim is back up to 12 ug/dl and by 12 hours it's up to 13 ug/dl. At this point 13 ug/dl is definitely not low enough for Max to see any improvement in symptoms and without a second dose at 12 hours, the cortisol will continue to rise.

By adding an evening dose at 12 hours, there is an overlap between the two doses that is high enough to drop cortisol down to a therapeutic level at some point during that second 12 hours. That overlap could equate to a dose of 75mg or 90mg at some point which is enough to keep the symptoms at bay but not enough to maintain cortisol within the acceptable therapeutic range (below 9 ug/dl).

If all of Max' symptoms have totally resolved, I would tend to agree with Kim that a post stim of 12 would be okay; however, there is no way for any of us to tell if a post stim of 12 is too high to normalize all abnormalities that we usually see on bloodwork and urinalyses for most cushdogs. That's a call your vet needs to make.

I see that you posted while I was typing so I now know that all of Max' symptoms have not resolved.

Sarah&Max

07-22-2010, 11:04 PM

labblab

07-23-2010, 09:51 PM

Thanks! So I guess my question now is... should I suggest that we go back to once a day dosing, or should I just see what happens after a few days of this twice a day dosing? I can't imagine I'm the only person on here treating her dog with trilo twice a day, am I?
Hi Sarah,

No, you are not the only member here who treats twice a day. But I think the more typical route of arriving at twice-daily dosing is the one that we have described above: FIRST establishing a therapeutic once-daily dose, and only then incorporating a second dose if symptoms are not resolved adequately throughout a 24-hour time period. So as I've said earlier, if it were me, I would have preferred to increase the once-daily dose prior to shifting to dosing twice a day.

Having said that, I'm glad to hear that Max is improving. But as far as the lack of improvement in the testing results -- his entire testing history has really been weird. Perhaps one explanation for the current lack of testing improvement might be a result of his metabolizing the drug really quickly so that there is little overlap between the two doses? In that case, since his morning dose has remained unchanged, perhaps his morning ACTH has largely remained unchanged as well? I dunno.

Anyway, I know I'm sounding like a broken record here. But I would not have shifted yet to twice-daily dosing. I would have first added the extra 30 mg. to the morning dose and gone from there. So I really can't offer an opinon about continuing to increase the evening dose at this time.

Marianne

O'Riley

07-25-2010, 12:24 PM

Hi Sarah....I've been reading your thread and wondered if you could answer a couple of questions:

When does Max eat? Does Max take anything for his thunderstorm anxiety?

~Rosey

littleone1

07-25-2010, 12:40 PM

Hi Sarah,

You are not the only person on here with twice a day dosing. Corky has been on twice a day dosing for 3 months now. He was only taking Trilo once a day for 6 months. His clinical signs were resolved, but his cortisol level kept increasing. His dosage had been increased and then had to be increased again. This is when he was put on the twice daily dosing. After 1 month, his cortisol level dropped a little.

Each individual furbaby will react differently. Even though there are protocols that really help, there are times when you need to go with your gut feelings and instincts.

Terri

Sarah&Max

07-26-2010, 11:52 AM

Hi Rosey--to answer your question, Max eats between 7 and 8 in the a.m. and then between 3:30 and 5 in the p.m. I was giving him the second dose exactly 12 hours later (so splitting up his evening meal into two) but just recently began giving it with his dinner.

He does take xanax for thunderstorms. i asked the vet about that--the last time we had a stim test it was the morning after a very bad night of storms. She didn't think that would cause such a small increase (she thought if it was the stress affecting the test, the results would be even higher.)

Terri--glad to hear there are others who have had to do things outside of normal protocol. Max's dose had been increased 3 or 4 times before this most recent increase.

So far, the 60 a.m./60 p.m. is working out really well. he passed a "test" last night that he hadn't in about a year--we always go to visit our families on sunday nights and max stays home for about 6 hours alone, with no bathroom breaks. We returned to find NO accidents, which was so great!

One more really cool affect of the drug finally seeming to work is that Max is MUCH more snuggly than he's been in many months, which I think must mean that he's feeling better! He used to (before the diagnosis) run around the house and then come flying into the living room and jump on the couch next to me for some cuddles. He did that last night after not doing it for a really long time! Made me so happy!

Boxer_lover

07-26-2010, 01:36 PM