Synacthen shortage

[Alison]

I'm in the UK and for months now, we've had an extreme shortage of Synacthen for the ACTH Stim Test. From what I've read, the manufacturer has sold the rights to it but the new owners aren't or don't even intend manufacturing it.

It means that Cairo's not had his stim test to see how he's doing on the vetoryl. His last test, done just after Christmas was baseline cortisol and electrolytes - the vet hoped that supplies of synacthen would be back up and running in time for his next scheduled test.

Well, that's next week and there are still no supplies.

The receptionist has said that Dechra UK have issued guidelines and have stated that the ACTH Stim Test is not necessary for monitoring - baseline cortisol and electrolytes are more than sufficient.

I'm a bit suspicious of this - we were told that regular stim tests were essential to make sure his dosage was correct and that he wasn't heading towards Addison's. Suddenly, now because they can't get the drug to do the stim test, it's not essential to carry one out.

My mum fell out with one of the vets today - he said that Cairo didn't need the stim test - that he looked at his results and they're fine - if anything his cortisol levels were a bit on the low side.

That worries me even more.

Am I worrying over nothing? Is the stim test necessary - or have I been paying a fortune for something that wasn't needed up until now - or are they only trying to placate me because they don't have the necessary drug?

[goldengirl88]

I spoke to Dechra a few days ago concerning my Tipper and asked if a baseline
Cortisol would suffice instead of a stim and I was told no. This is very disconcerting to learn what they told you, as it is totally opposite. Good luck I hope you can get the help you need. Blessings
Patti

[Alison]

Dechra UK have apparently issued guidelines saying that baseline cortisol and electrolytes are perfectly acceptable. I had emailed them before regarding dosing and they wouldn't entertain me at all - told me that I needed to speak to the vet.

I might actually email Dechra USA and UK and ask the same question and if they give different answers, then I'll want to know why. :mad:

[Alison]

Hmm, I have a feeling if I try to email Dechra USA, it'll get diverted to the UK site as it asks for the country of origin.

I've emailed UK Dechra to ask the question - I'll see what they say.

Also - we were told that Cairo had to be fasted on the day of his ACTH Stim tests, yet I've just read that it's really important that the vetoryl is given WITH food on the day of monitoring as food helps the absorption of it.

Do you guys fast or feed on the day of testing?

[lulusmom]

You must give Vetoryl with food for proper absorption. If you fast the dog before the test, the results will be useless. If your vet wants to do other blood tests that require fasted samples, then you will need to schedule two appointments.

I did find some information on the Synacthen shortage on the VMD website which I have copied and pasted below:

Synacthen


The VMD is aware of a European supply problem with the human authorised product Synacthen, PL16853/0017. Synacthen is a synthetic ACTH, indicated as a diagnostic test for the investigation of adrenocortical insufficiency. It is used for the diagnosis of hyperadrenocorticism (Cushings), hypoadrenocorticism (Addison’s) and for monitoring trilostane therapy in cats and dogs. Normal stock levels are due to return to market from the middle of October 2013 but priority will be given to human supply.

If veterinary surgeons are aware of any other alternative products, you may submit import certificate applications for these. Each application will be assessed on its individual merits.

If you would like further information on Synacthen, please contact Alliance Pharmaceuticals Limited on 01249 466966.

For further veterinary advice on how to monitor dogs treated with trilostane in the absence of synthetic ACTH, please contact Dechra Veterinary Products on 01939 211200.

It very well may be that there is no alternative to Synacthen in the UK and other European countries so the only thing you can do is a use symptoms, resting/basal cortisol and electrolyte check as your guide. It's certainly not optimum but if there is no alternative stimulating agent, there's not much else you can do. The stimulating agent of choice in the U.S. is cortrosyn so there is no shortage here. I doubt that Dechra U.S. would offer any feedback on this subject and would probably refer foreign pet owners to Dechra UK.

According to the VMD, your vet can submit an import application for an alternative product and cortrosyn is definitely an alternative product. As a matter of fact, most specialists in this country think it is superior to Synacthen/ACTHAR gel. Cortrosyn is manufactured by Amphastar in California. You can find info at http://www.amphastar.com/cortrosynwhatis.htm

Glynda

[molly muffin]

No, the guidelines and the top specialist in cushings, all agree that you do not fast prior to an ACTH once treatment has been started. You give it regularly with the food in the morning and then test 4 - 6 hours later. 4 preferably.

I don't think Dechra USA will answer, one of our members in Canada (where I am tried) and was told they only speak to vets. Here it isn't even called Dechra, but something else and the it seems they speak to the sales rep. Rather crazy system in my mind.

I've always been told that you need ACTH testing to monitor levels and that is certainly what is recommended usually in the states.

The problem is going to be what to do with all the animals that need monitoring and without the drug to do it. I think they are going to have to go to a different agent to us rather than Synacthen. There are gels that can be used but then you have to test at 2 hours rather than 4 hours and they are not as reliable as a synthetic cosyntropintherapy.

This is a link that talks about the different stimulating agents a bit and is from Dr. Peterson a well known endocrinologist.

http://endocrinevet.blogspot.ca/2013/11/protocol-for-acth-stimulation-testing.html

Still it might be better than nothing.

Sharlene and Molly Muffin

[molly muffin]

Glynda and I were typing at the same time and her reply is spot on.

Sharlene and Molly Muffin

[Alison]

Thank you ladies. The really stupid thing is, I managed to track down some supplies of synacthen today and needed a prescription from the vet. Our normal vet is part time, so we ended up speaking to one of the partners who got quite shirky about it and said that it wasn't necessary and we shouldn't be trying to order things online - he's one of them that thinks all meds should be bought via the vet (at a greatly marked up price) because you could be ordering anything online.

So he refused a prescription. I'll be having it out with our usual vet on Tuesday - if we don't get anywhere, I think we need to find another vet.

Cairo has always been fasted prior to all his tests - under the vet's instruction so now I'm worried that his results are totally wrong.

He's been ticking along nicely too and I know that they say to keep an eye on him for symptoms but a couple of months ago, after his stim test, we stopped on the way home for a play and a run about when the vet phoned - his cortisol levels had dropped to 17 and we were told to stop the vetoryl for 10 days and then redo the stim test - and yet he was showing absolutely no symptoms of low cortisol and that's why I worry so much.

[spdd]

This just makes my blood boil when I read what vets are doing. Wouldn't you think that they would take the best interest of the dog to heart and not the almighty dollar which it seems most of these vets only think about. I am really P%%^^& when I read this stuff.

I was the one that tried to reach Dechra in the U.S. and was told point blank that they do not deal with any pet owners outside the U.S. The only other place I could go to was a division in Quebec and they've never even heard of the manufacturer dealing with pet owners. Go figure!!!!! Again blood is boiling. No help at all.

I sure hope you get some answers soon. Maybe you need to be like Patti and myself and go in swinging. I have been to hell and back with vets in the last few months, so much so that I even had one vet refund me $1200.00 for their poor care and wrong diagnosing of my dog. Hang in there - you know like the rest of us we are the only advocates our babies have. Because of my persistence my dog now has been with me for 7 months more then expected, just because a vet wanted to put him down saying there was no hope. He's actually better now then he's been in a long time.

Good luck...

[Alison]

The actual vet we see is lovely but it was a partner that my mum spoke to yesterday - and all he's interested in is you buying meds from them because you can't trust what you get online - but they charge almost twice what I'm paying for Cairo's Vetoryl so there's no question for me where I'm getting it from. The vet we see though gave us a repeat prescription so that it was only one prescription we were paying for so she's on our side in that respect.

I managed to find an online pharmacy that had supplies of Synacthen and I'd went in yesterday to ask for a prescription so that he could get his stim test - and that's when that vet refused.

He said that these places shouldn't be selling synacthen to the public - but they're not selling it to me - they're fulfilling a prescription issued by the vet.

When I first spoke to the receptionist and told her I'd source some supplies, she told me that they weren't allowed to order online and I said to her that I could if they issued me with a prescription. She wailed that that wasn't fair - that Dechra had issued guidelines that synacthen supplies were only to be used in emergencies for diagnosis and if I was using up supplies for an unnecessary test, it meant there wouldn't be any supplies for emergencies - but if she's not allowed to order online, how would that affect her anyway?

I emailed Dechra UK and asked if the dog should be fasted prior to the stim test and also if baseline cortisol and electrolytes was adequate monitoring.

They said that the dog should NOT be fasted prior to the test but they wouldn't answer me about the stim test - said I had to discuss it with the vet and that protocols were in place for vets but they would only discuss it with the vet and not the pet owner.

The Veterinary Medicines Directorate are confirming that there is a European shortage of synacthen (and I know why - found a couple of articles on it) but if vets wanted to apply to import alternatives, then they should apply to the VMD and each case would be dealt with on an individual basis.

I know that the alternative is cortrosyn, available in USA but that twit of a vet said that was rubbish - there were no alternatives.

I really could swing for him.

[lulusmom]

I think it's telling that this vet lectured you about the necessity of synacthen and ordering it online? He apparently also thinks its unnecessary to educate himself on a very serious drug he has prescribed so as to safeguard the well being of his patient. The various labs who receive blood samples do state to fast a dog for an acth stim test but that protocol does not apply to dogs being monitored for Vetoryl treatment. Rather recently, I wrote to a lab in the UK who erroneously stated that a fasted sample was necessary for monitoring Vetoryl treatment. I told them that ignorant vets would simply follow their instructions, thereby placing the patient at risk. Your vet is a perfect example. While their solution wasn't great, they did revise it to include that Dechra recommended administering the capsule with food.

There is plenty of information on the Dechra website for veterinarians who want to learn but if that's too much trouble for your vet, he could have at least taken the time to read the packaging insert, which clearly states that the capsule should be given with food. A fasted blood sample is a waste of your money but more importantly, it places dogs at undue risk. Without the benefit of food, the drug is not properly absorbed so one must assume that cortisol levels will be higher. If a dose increase is made based on these inaccurate results, it could be disastrous for a dog. If anybody should be lectured to, it is your vet for placing Cairo at risk and wasting your hard earned money. There is no excuse for this kind of ignorance but unfortunately, we see it day after day. Thank goodness Cairo has a proactive mom. Way to go!

The information you sought from Dechra can be found in our Helpful Resources library, as can a wealth of other information. I have provided links below to resources that I would suggest you print out and provide your vet while giving him a tongue lashing. :D Hopefully he will use these for future reference.

Dr. Mark Peterson is renown expert, worldwide lecturer and frequent contributor to Dechra's continuing education program for veterinarians. He maintains a blog for vets which many of us subscribe to. Here is a link to his protocol for acth stim tests. If you will go to the bottom of the page under "Bottom Line", you'll see that he clearly states no fasting for stim tests.

http://endocrinevet.blogspot.com/2013/11/protocol-for-acth-stimulation-testing.html

This link comes directly from Dechra and is their treatment and monitoring protocol. The chart specifically says give the capsule with food. Directly below the chart is the packaging insert. On the right hand side, a little over half way down the page, you will see the Clinical Pharmacology for this drug which reads:


Trilostane absorption is enhanced by administration with food. In healthy dogs, maximal plasma levels of trilostane occur within 1.5 hours, returning to baseline levels within twelve hours, although large inter-dog variations occur. There is no accumulation of trilostane or its metabolites over time.

http://www.dechrace.com/pdfs/vetoryl/vetoryl_treatment_monitoring_hyperadrenocorticism. pdf

[Alison]

Thank you Lulusmom.

It was actually Dr Peterson's blog that I came across and saw that the dog wasn't to be fasted. I had started off looking for confirmation that baseline cortisol and electrolytes was adequate and that's when I found out about the necessity for food prior to the stim test.

I'll be honest, my biggest problem is that the vet won't take onboard anything that isn't UK based. "That's America - it's not the same here". I've noticed though that Dechra's US site has a lot more information than their UK site. I will be printing off the necessary information to take with us though. I'm so angry and upset. It's not to do with the money spent - though it certainly goes into hundreds and hundreds of pounds potentially wasted - it's the fact that there's every chance that the test results have been inaccurate.

To tell me that his last test showed his cortisol to be slightly on the low side (fasted) to me means that his cortisol levels would have been even lower had the test been carried out with food.

This same vet, who I've only ever seen once before with our old dog who has since gone to the Bridge, was going to have us pts him based on blood results which were catastrophically wrong - I was refunded the cost of these tests which was an admission that they were wrong. I refused ever to see this particular vet again so you can imagine how my heart sank when it was him that phoned us yesterday.

I have no problem arguing with him but the fact that our normal vet is such a nice lady makes it harder to rant at her! I'll start off nice though and see how it goes but if ranting is needed, then I'll rant.

[Renee]

Good for you Alison. Sounds like you are an excellent advocate for your dog.

I am confused about why the US has access to so much information and the manufacturer directly... and, yet, the UK and even Canada are kept out of the loop so much. This confuses me. Is veterinary medicine that different between the countries?

[Alison]

I don't know - it's so frustrating - after all, we're paying our vets to treat our animals so our wishes should be taken into consideration. It's almost like doctors/vets all have this belief that a mere patient couldn't possibly have any understanding of what's going on.

[Squirt's Mom]

You might the vet what the difference is between the drug Vetoryl itself in the US and the Vetoryl in the UK. I doubt they will find one. ;) If the drug is the same in both countries, why would the approach for using it be different simply because "that is in America"?

[lulusmom]

To tell me that his last test showed his cortisol to be slightly on the low side (fasted) to me means that his cortisol levels would have been even lower had the test been carried out with food.

That is absolutely correct. Since your vet seems to be very inexperienced in treating cushing's, I'm wondering if s/he may also not know how to assess an acth stim test for purposes of monitoring treatment. I had a gp vet who told me my dog's cortisol was too low and recommended I discontinue treatment. The stim test was perfect, the vet's education was far from perfect. He was using the normal reference ranges for a normal dog and I'm wondering if this is what your vet is doing. Can you please obtain the results of Cairo's last stim test and post them here? It's only two numbers so even if you can't get the hard copy, you can probably call and get the pre and post number from the vet.

Glynda

[lulusmom]

I forgot to mention that you can't get any more UK based than the manufacturer of Vetoryl. The fact of the matter is that most of the well published veterinary endocrine experts are in the U.S. and Dechra acknowledges their expertise by using their names and their expertise in educating vets. This is an excerpt from one of their pages on their site:


Dr. Mark E. Peterson is a world-renowned specialist in veterinary endocrinology, specifically diabetes, hyperthyroidism, hypothyroidism, Cushing's and Addison's disease. Dr. Peterson served as head of endocrinology and nuclear medicine at The Animal Medical Center in New York for over 30 years. He now sees patients at his private practice, the Animal Endocrine Clinic (New York City and Westchester County), the only veterinary hospital devoted entirely to animals with endocrine problems.

http://www.dechra-us.com/Cushings-Syndrome/Veterinarians/What-is-Cushings-Syndrome-1.aspx

You will also find two other U.S. contributing experts on their Veterinary Continuing Education Learning Center, Dr. David Bruyette and Dr. Audrey Cook.

http://www.dechrace.com/canine_hyperadrenocorticism.shtml

[Alison]

I'll ask when we go on Tuesday - our own vet isn't in until then and I'm not dealing with anyone else - not after yesterday (still fuming about that guy).

I'm trying to remember his results, off the top of my head.

He was started on 120mg and first stim test brought levels down to 80-odd (I'm assuming these figures she gave me were post-stim)

He was due for his second stim test but our vet was on holiday so we had to see another one. Our own vet had said, depending on his results, she intended halving his dose to 60mg. This other vet said his levels were 137 and he was to stay on the 120mg. I was none too sure about this, but we did as we were told and waited on our own vet coming back.

Next stim test, we got a frantic phone call from the vet saying his cortisol levels were only 17 and to stop the vetoryl for 10 days and he was to get a repeat stim before re-starting. This was the occasion that we were out playing so he had no signs of low cortisol!

His next stim was in the high 700's so he was restarted on 60mg vetoryl.

This is where I can't remember even roughly what his next stim was - the vet had said that as long as he was between 50 and 150, she would be happy. I've a feeling that the next one was maybe in the 60's.

He was to continue on the 60mg but he's never had another stim test because that's when synacthen supplies ran out, so his last test was baseline cortisol and electrolytes. I'll see if my mum can remember figures.

I'll definitely ask for his test results though when he's there on Tuesday.

[Alison]

Oooh, I'm really very impressed. I messaged Dr Peterson this morning - never expecting a reply - but he has replied. Not sure I know what he means but hey, he replied. :)

Here's our communication:



Dear Dr Peterson,

My staffordshire bull terrier was diagnosed with Cushing's in August 2013.

He has been on trilostane since diagnosis, with regular ACTH stim tests.

There is now a European shortage of synacthen and we've been told that any supplies left are only for emergencies and he is no longer to get the ACTH Stim test. The vet has said that baseline cortisol and electrolytes is more than adequate to monitor his dose.

This is causing me huge amounts of concern as his dose had been changed from the starting dose and we now don't know how he's doing when stimmed.

I'm sure the vet could apply to import an alternative (I assume cortrosyn) but they've told me there is no alternative.

In your opinion, is baseline cortisol and electrolytes adequate for monitoring?

We've been told to also monitor clinical signs but that's not a good guideline for us, as we got a phonecall from the vet to tell us his cortisol levels had dropped to 17 and to stop the trilostane - yet at that precise moment, he was a happy boy, running around at the park and having a ball - he wasnt showing any signs of low cortisol. Thank you for your time, Alison



I know this is a big problem, which I don't have an answer for in these cases.

Monitoring basal cortisol values is fine to look for overdosage. So in your dog, stopping the trilostane and then retesting in 2-4 weeks is a good idea. Once the cortisol value goes up again (generally to >1.5-2 ug/dl or >30-40 nmol/L), the the drug can be started once again.

The problem with basal cortisol valeus that that we really have no idea when we can raise the dose of the drug. Certainly, dogs that remain polydipsic and polyuric on a standard daily trilostane dosage should be changed from once daily dosing to twice daily, divided dosing.

In other words, if a dog is on 60 mg once daily and remains symptomatic, this dose should always be divided and given as 30 mg twice daily before we go up on the total daily dose.

[Renee]

That's great that you got a reply! And, twice daily dosing is a great idea, before upping the total dose.

[Alison]

I probably didn't explain things very well in my original communication. His dose has been halved and I'm sure our vet has absolutely no intention of increasing his dose again - she wants to keep it as low as possible.

My worry was only baseline cortisol being used to monitor and it sounds like Dr Peterson is saying that's OK as there's not a lot else we in the UK can do at the moment.

Whilst he has no chance of getting a stim test, there's no way I'll be letting them even attempt to raise his dose anyway. He's doing OK on his current 60mg dose - unless of course his levels are too low - and as far as I'm concerned, he'll stay on that dose - unless it needs reduced.

[lulusmom]

What Dr. Peterson was saying is that if the current acth stim test yielded a post stimulated cortisol of 17, that would be dangerously low and dosing should be discontinued until the basal cortisol has risen to within the range he mentioned in his response. He has provided two ranges, one in the reporting units that are normally used by labs here in the states, being ug/dl and the other in reporting units used by labs in the UK, being nmol/L. Since your dog's cortisol profile has changed since that low stim result, Dr. Peterson's first comment would not be relevant. His second comment would apply to your dog's present status. You can't use the basal cortisol to determine when you need to increase a dose as a post stimulated cortisol doesn't always correlate with the basal cortisol. Therefore, you'll have to wing it by using a combination of symptoms, basal cortisol and electrolyte checks. The only good news is that checking basal (resting) cortisol is certainly cheaper than a stim test.

Glynda

[Alison]

Thank you. That all makes sense. It was so nice of him to reply as well - really didn't expect it.

You'd think that it would be cheaper than the stim test - but it wasn't - it was near enough the same price - but I was charged a consultation fee, plus a fee for the blood draw, plus the cortisol and electrolytes testing.

That's added to my list of things to speak to her about as well!

[Alison]

Oh, I know what I forgot to ask - I have a spoiled boy - he likes one egg scrambled for his breakfast - is that enough food for his vetoryl?

[lulusmom]

One very large or jumbo egg should be enough.

[Renee]

Is an egg all he gets for breakfast?

I had a question on the food & vetoryl, and when I emailed Dechra they replied back that vetoryl should be given with a full meal, not a snack or treat or small meal, but the full meal.

[Alison]

Yeah, he used to only get one meal a day - he's the kind of dog that if he got even a third of his daily allowance for breakfast, he wouldn't eat his dinner. He just likes to have something in the morning (though I think he steals a bit of my mum's toast as well!)

I think we might need to think about adding some extra in on his breakfast though. I didn't realise about the food until recently.

[Alison]

Just got Cairo's baseline cortisol results. He's sitting at 67 and the vet is happy with that. His cortisol last time was only 55 which was a bit lower than she'd have liked.

He's also lost a bit of weight - not much - he's down from 28.2kg to 27.5kg but it's a step in the right direction.

She tells us that the synacthen is back in stock at the pharmacies but they haven't got any supplies yet.

[lulusmom]

For those members used to seeing cortisol values in ug/dl, the conversion is 2.4 ug/dl, which is a good number.

[Alison]

Thank you - I didn't know what it was in ug/dl.

The vet says he's looking well. It's hard for us to see it I think but she thinks he's looking less bloated, has a sparkle in his eyes, coat is shiny and he has his mojo back :D

That's the longest he's been between tests - his first 3 months milestone (even though I was two weeks early - couldn't bear waiting any longer).

[lulusmom]

I believe the basal cortisol value you posted is in nmol and to convert to ug/dl, you divide by 27.59. I should have explained that in my prior post.

[molly muffin]

That is a very good baseline. :) Great news.

Also it's wonderful to hear that Synacthen is back in stock, so test as needed can resume soon too.

Sharlene and Molly muffin