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Author Topic: cyclosporine  (Read 272 times)

jacky

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cyclosporine
« on: October 07, 2018, 02:09:32 PM »

Hi my two year old papillon has imt since she was 9 months old.We have managed to wean her of steroids three times but each time she has relapsed within 6 weeks.We are now at the weaning of stage and are down to 5mg split over the day she weighs 6kg.
My vet has suggested giving her cycosporine as well as the preds.Her platelets at the moment are 500 she is doing really well not really having any side effects and i just dont know what the advantage would be in her having cyclo.

kind regards Jacky.
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Catherine

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Re: cyclosporine
« Reply #1 on: October 08, 2018, 11:55:47 AM »

What sort of medication protocol was she put on? Could she have been weaned off too quickly? Here is a good protocol:


Immunosuppressive Protocols for Oral Prednisolone in the Dog.
Ref: Clinical Immunology of the Dog & Cat by Michael J Day  – Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.

This example is based on a dog receiving an induction dose of 1.0mg/kg/q12hrs (every 12 hours)

Dose                Duration (based on clinical effect)

1.0mg/kg/q12h             10-28 days
0.75mg/kg/q12h            10-28 days
0.5mg/kg/q12h             10-28 days
0.25mg/kg/q12h                         10-28 days
0.25mg/kg/q24h                         10-28 days
0.25-0.5mg/kg/ Every other day      at least 21 days
0.25-0.5 mg/kg/ Every third day       at least 21 days

Azathioprine (a cytotoxic drug) can be used in combination with prednisolone at 2mg/kg/24 or 48 hrs and dose gradually reduced, when remission is achieved, over a period of months.
Clinical response to Azathioprine may take up to 6 weeks. (Plumb’s Veterinary Drug Handbook)

Don't forget the gastroprotect

I, also, can not see the advantage of giving Cyclosporine and some dogs have bad side effects on it.















































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jacky

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Re: cyclosporine
« Reply #2 on: October 08, 2018, 03:35:33 PM »

Yes I think she was weaned of too quickly! My vet also her specialist seem to want to get her of steroids as quickly as possible,.even when i insist that it be done more slowly.
I am following the protocol on here now (vet is unaware of this) she is doing really well.I feel that after the relapses she has had that she may need to stay on a small amount of pred.(what would be considered a low dose for a 6kg dog?)
my vet has told me she strongly disagrees with me not letting her have the cyclo and that she cannot stay on steroids.
This site has been a godsend to me and thankyou for the reply.
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Catherine

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Re: cyclosporine
« Reply #3 on: October 08, 2018, 05:16:44 PM »

If your dog is coping well with the steroids then it is best to go slowly weaning her off otherwise if she relapses she has to have high doses again which is probably worse then continuing on a small dose. I am not sure what a small dose would be for a small dog. I do know several owners keep their dogs on a very low dose, too low to be immunosuppressive but it does seem to keep their dogs ticking over okay.

Has your vet said why she wants to put her on Cyclosporine?

I have found a thread on here where the author has written a detailed description of her dog's experience with the medication for IMTP. You may find it helpful. See here: http://cimda.co.uk/smf/index.php/topic,935.msg8546.html
If you want to see more posts by DW just click on DW on the post and then "show posts". She mentions using Melatonin.
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jacky

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Re: cyclosporine
« Reply #4 on: October 09, 2018, 02:11:42 PM »

Thankyou for the link,very helpful.The only reason she gave for the cyclsoprine was that she she has relapsed three times when coming of preds and she didnt want her to stay on preds as eventually she would have side effects.
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Catherine

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Re: cyclosporine
« Reply #5 on: October 09, 2018, 08:51:43 PM »

So how long has she been having the steroids this time and what dosage was she started on? I am presuming her platelets are within normal range now.

I have to say that I have had no personal experience of Cyclosporine but if your dog's platelets are back to normal I can not see the benefit of starting her on Cyclosporine. If the Preds have done their job then it would seem to me that the Cyclosporine would not be of any benefit. Perhaps some other member will understand it more. I do, however, think the low dose of Preds could benefit as others seem to think that.

If she is doing okay on the 5mg you could reduce that even slower and have regular blood tests to keep an eye on things.
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mon67

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Re: cyclosporine
« Reply #6 on: October 10, 2018, 02:24:43 PM »

Hi Jackie

how much steroids was she having when she relapsed.
My vet said that an unacceptable amount of pred is 0.4/0.5 mg/kg every other day.
Of course the Pred is a miraculous drug, but ideally the dog should go into remission, so ideally you should be able to wean her off all medications.
This is not possible for everyone, but I think you should at least give it a try.
Personally my dog was on high doses of Cyclosporine for a while. Honestly she did not have any benefit from it, but I have read some other cases where it actually worked really well.

Why is the vet suggesting this particular immunosuppressant? There are plenty more that you can try maybe more specific for IMHA.

Cheers
Monica
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jacky

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Re: cyclosporine
« Reply #7 on: October 10, 2018, 04:45:18 PM »

The longest she has gone without medication is six weeks.Her last relapse was august platelet went down to 12,she was put back on 15 mg preds, platelets  then rapidly increased,so weaning of started again we went from 15mg to 10mg to 7mg and are now down to 5mg these doses are split over the day,platelets are now 400 and she is a happy playful dog.
I am just unsure where to go from here,or what advantages we would gain from the cyclosporine.
She was given immuran in the past and suffered some nasty side effects.
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Catherine

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Re: cyclosporine
« Reply #8 on: October 10, 2018, 05:50:18 PM »

If she has been coping well with the Preds then that is way too quick a decrease in medication, in my opinion. I would have thought , given the previous two relapses that your vet would have reduced slower. Was the reduction the same the previous two times? What was the problem with Immuran? Perhaps the dose was too high. I do know the liver levels can increase but they usually return to normal when the medication is reduced.

I would be reluctant to start the Cyclosporine for the moment. When is her next blood test?
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Jo CIMDA

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Re: cyclosporine
« Reply #9 on: October 10, 2018, 06:02:05 PM »

Hi Jacky

I understand your vet's concern  about having a 'combination' drug to support the preds but as your girl is doing well and her platelets are in normal range I also agree with you and the others and wonder if adding cyclosporine at this stage is necessary.   If the side effects of the preds allow how about taking these last reduction  stages very slowly perhaps by reducing the preds by 1mg each time and with a few weeks between reductions.   

Cyclosporine works for some dogs but not for others and there is no way of knowing how she will respond.  It can upset the tummy, but many immunosuppressive drugs can until the dog is used to it.

As Imuran  didn't agree with her, if you do have to consider another drug there are others such as  mycophenolate and leflunomide that might be worth consideration.  This gives the options.

http://veterinarymedicine.dvm360.com/immunosuppressive-drugs-beyond-glucocorticoids

As already mentioned, melatonin might be worth considering. In addition to the links by DW, see this link.

https://www.mspca.org/angell_services/melatonin-for-primary-immune-mediated-thrombocytopenia-itp/

Jo
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jacky

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Re: cyclosporine
« Reply #10 on: October 11, 2018, 02:54:50 PM »

Thankyou all so much for the advice.This is actually the forth time we have tried to get her of steroids.She seems to do really well on 2mg twice a week and was on this dose for two months my vet then insisted she came of medication a couple of weeks later she had relapsed.
I agree that things should be done much slower and will do that with or without my vets consent.As Jo suggested I will reduce by 1mg at a depending on bloods.
My vet has also insisted that I should regular flea and worm her (bravecto) I have done neither off these since I found this site.
Maybe It Is time to change vets.
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Jo CIMDA

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Re: cyclosporine
« Reply #11 on: October 11, 2018, 08:46:56 PM »

Wow.  Well done for taking some control.  It is important to have a vet who will work with you and he or she listens to your concerns.

Avoid all chemicals if you can and only worm if you see worms, and unless she has a problem with ticks and fleas again, stay away from  Bravecto and any other harsh chemical preventative treatments and vaccines etc.

Some dogs have to stay on a low dose of pred and although it isn't ideal if this is the only way to have a good quality of life then so be it.   I hope, if you do this very slowly it will work. Fingers crossed this time she will be in long term remission. 

Jo


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jacky

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Re: cyclosporine
« Reply #12 on: October 12, 2018, 05:44:52 PM »

Thank-you for your advice, which I will follow.Can I just ask what would be a reasonable amount of time between reductions? obviously dependent on blood results.
I will keep you updated on our progress.
    kind regards Jacky.
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Jo CIMDA

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Re: cyclosporine
« Reply #13 on: October 12, 2018, 09:53:22 PM »

Hi Jacky

I am sorry I can't be specific, but you can be guided by the Michael J Day protocol, which is the best I have come across.  Reductions in dose and duration of pred depends on the resolution of the AI  disease, and also the clinical signs that the side effects produce.  Sometimes if the side effects of the drugs are severe the dose has to be reduced quicker than the ideal duration, so it is difficult for anyone other than you or your vet to say when the dose should be lowered and what duration you should have between reductions. Visible assessment is needed. 

When the clinical signs and blood results of the AI disease indicate that the disease is in remission, it is often better to eek out the duration to maximise the effect of the drugs, but this can only be done if the dog is coping with the drug induced side effects, so with the recommended protocol in mind if you get to say 10 days and the dog is coping well with the side effects of the drugs then take that dose to 12 days and assess again.  If things are still good and the dog is eating and drinking well and is still able to get up on its feet without too much trouble etc.,  then the duration can be extended to 14-16-18-21 days etc....... This is always tailored to the individual.  I will copy some information about what to expect when treatment has started and this gives indication of the warning signs to look out for when the preds are having an adverse effect. 

If you want further clarification, please ask.

Jo


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Jo CIMDA

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Re: cyclosporine
« Reply #14 on: October 12, 2018, 09:58:18 PM »

WHAT TO EXPECT ONCE TREATMENT HAS STARTED
If a dog has a serious autoimmune disease, then the sooner treatment commences the better chance the dog has of survival.  The main delay to starting treatment is obtaining a diagnosis or at least your vet being sure that he hasn’t missed anything that could be made worse by giving high doses of steroids.  Achieving a diagnosis can be a fight against time. 
If your vet has decided that in all probabilities your dog has an autoimmune disease, then to a certain extent, which autoimmune disease your dog has, as far as treatment is concerned, is irrelevant because with the exception of a few diseases, they are all treated the same, that is, with immunosuppressive drugs.  The main objective is to ‘knock out’ the immune system and virtually stop it from working (or near enough) so the destruction will cease and give the body a chance to recover.  As previously stated, this treatment regime works in most cases, that is, if it has been given early enough and the dosage is correct.  All dogs are different and some can tolerate the drugs better than others. In proportion to their size, small dogs seem more able to tolerate higher doses of steroids than large ones. Some diseases are more serious than others and carry a poorer prognosis. So the initial crisis is a crucial time, however anecdotal evidence shows that many more dogs survive than die if correct treatment is administered in good time.

It is hoped that a positive response can be seen within 4-6 hours of starting treatment (depending on the disease), but in a serious, life threatening situation, the first 2-7-14 days can be a very worrying time.  Assuming the dog has stabilised he will quickly feel much better, and if he is in hospital may be allowed home within a week.
When he comes home he will probably have a ‘goody bag’ full of drugs.  He will be on a high dose of steroid, usually prednisolone, and he may also be on another immunosuppressive drug, such as Azathioprine.  Your dog will be weaned off in a controlled manner according to his wellness and clinical observations. 

Note: High doses of steroids must not be stopped abruptly.  Your dog could go into an adrenal crisis if the medication is withdrawn too quickly. 

In addition to immunosuppressive drugs he should have something to protect his stomach from excess acid.  The last thing your dog needs when he is feeling poorly is a bleeding stomach ulcer caused by the drugs.  Sometimes, Antepsin is given to coat and protect the stomach (but this must not be given within two hours of other medication otherwise it will stop the drugs from being absorbed).  Zantac (Ranitidine) may also be prescribed to take away the excess acid. Another gastroprotectant used is Omeprazole. To minimise irritation to the stomach it is usual for the daily dose of steroid to be split into two doses and given with food, one dose in the morning with breakfast and the other dose with his evening meal. I have known several dogs, who did not receive a gastroprotectant as a part of their treatment regime, and went on to develop anaemia. This is not autoimmune haemolytic anaemia but iron deficiency anaemia caused by bleeding stomach ulcers. Using a gastroprotectant is a good preventative measure. When the steroids have been significantly reduced to a low dose, a gastroprotectant may not be necessary.

Excess acid, produced because of the drugs, may make a dog prone to developing pancreatitis. A dog with pancreatitis will appear in pain and his back may be arched as if he can’t straighten up.  He may be lethargic, seem bloated and have a tender abdomen. Dogs usually go off food and water, may vomit and look depressed.  If you suspect that your dog has pancreatitis, don’t try to feed him because it will make the condition worse. Take him to the vet as soon as possible as he may require treatment or need to go on an intravenous drip to stop him dehydrating.  Again, the risk of pancreatitis should be minimal once the dog is on a lower dose of steroids.   A low fat diet is best when your dog is on high dose steroids or prone to pancreatitis. 

As your dog‘s immune system is being significantly suppressed, he will be more likely to pick up infections, and will not have the ability to fight against them.  As a precaution a broad spectrum antibiotic is often prescribed. Also it is sensible not to exercise him in areas where he is more likely to encounter infections, for example, a park or a popular dog walking area.
 
Whilst your dog is on high dose steroids he will want to eat and drink excessively. However, this also means that he will want to urinate more and this can sometimes cause temporary incontinence.  You may have to get up to let him out during the night and if you leave the garden door open during the day, it may save some mopping up!  He cannot help it and won’t like it either, so don’t be too hard on him, it’s only temporary. You will notice as he is weaned off the drugs the unwanted side effects will subside and he should return to normal habits and behaviour.  Urinary tract infections and/or bacterial skin pustules are not uncommon when a dog’s immune system is suppressed, and this is often the reason for a dog to be off colour during this time.  Note: Always consider a urine infection if your dog seems under par.  A course of antibiotics will usually sort this out quickly.

Depending on what autoimmune disease your dog has, he will probably need to have regular blood tests.  Biochemical blood tests will also keep an eye on other body functions, such as those of the liver and kidneys, which is important at this stage.
Assuming good progress is being made, the clinical signs of his illness are diminishing and positive signs of improvement are apparent, your vet will want to start weaning him down from the high doses of steroid.  This process can take 3-6 months or more, and usually begins any time after 10 - 28 days from the start of treatment, depending on the results of his blood tests and his clinical signs.
Relapses are not uncommon, especially in diseases that are difficult to control, for example SLE.  A relapse may mean that initially, your dog needed to be on a higher dose of immunosuppressive drugs for a longer period of time, or your dog may have been weaned off a little too quickly and then the dose withdrawn too soon.
If a relapse occurs he will probably show similar clinical signs to his initial crisis.  He will have to go back on an immunosuppressive dose of prednisolone, but it may not have to be quite as high as before. A combination drug may need to be added at this stage. The weaning process will then have to start all over again. Returning to an immunosuppressive dose will mean that he has to go back on a gastroprotectant.

Side Effects of the Drugs – Iatrogenic Cushing’s Syndrome
Iatrogenic Cushing’s syndrome is a side effect of high dose steroids and is caused by too much corticosteroid in the body. To a lesser extent, the immediate side effects observed when the dog initially goes on steroids eg., drinking, eating and urinating excessively is a mild example of Cushing’s syndrome.  Personally I like to see dogs responding to high doses of prednisolone in this way, as it means that they are responding to the drugs as they should.
Usually, Cushing’s syndrome only becomes a real problem when exceptionally high doses, or prolonged high doses of steroids are administered, maybe due to a relapse, or in some cases where the vet is inexperienced in reducing steroid doses and keeps the dog on a high dose for longer than necessary; or when the dog is not responding to treatment and higher doses are necessary to control the disease.  This is where the cytotoxic drug Azathioprine is very useful. 
All drugs carry side effects and Azathioprine is no exception, but it does not carry the same side effects as prednisolone, therefore by using this drug in combination with prednisolone it reduces the risk of iatrogenic Cushing’s syndrome.  As Azathioprine takes at least 10 days to take effect, starting the ‘combination’ therapy at the beginning of treatment may enable the prednisolone to be lowered within the 10-28 day band and still maintain a good level of immunosuppression. If your dog is not responding to treatment then your vet may consider changing his treatment to other immunosuppressive drugs.

How Can I Tell if My Dog Develops Iatrogenic Cushing’s Syndrome?
Iatrogenic means ‘drug induced’.  Clinical signs of Iatrogenic Cushing’s syndrome are the same as primary Cushing’s syndrome but can present with acute clinical signs. It reflects the level of corticosteroid in the body.
The most notable side effects are, heavy panting, some hair loss, and an increase in drinking and urinating, excessive pigmentation.  This is something everyone seems to be aware of and accepts as normal when a dog is on high dose steroids. Very often the dog will be weaned down to a low dose before any major problems arise. 
Acute Cushing’s syndrome due to overdosing of corticoid steroids can be very serious.  Blood results will reflect this, especially the liver enzymes which may be extremely high. Red blood cells and blood platelets may also be high and blood clotting may be a risk.
So when should you alert your vet to suspected, unacceptable level of corticosteroid?  The owner should take note when other clinical signs occur, such as: Depression, anorexia, muscle wasting and extreme weakness, continuous panting, lethargy - unwillingness to exercise, skin lesions and thinning of the skin, excessive hair loss, pot-bellied appearance and sagging back, behavioural changes (aggression).
If your dog is showing these signs it will probably mean that the dose of steroids needs to be lowered. It is important that it is not confused with a relapse of the dog’s condition or an infection. The dilemma is that steroids must not be withdrawn too quickly otherwise the dog may go into an adrenal insufficiency crisis.  If the clinical signs of iatrogenic Cushing’s syndrome is intolerable, it is hoped that the high dose of steroids that he has been on will have already done their job and that his autoimmune disease will be stable. As long as the steroids are lowered in a controlled manner and in time, all the symptoms of Cushing’s will subside and your dog will return to normal, but extreme signs must not be ignored.

Reducing the Tablets
When significant improvement in the dog’s condition is seen, usually between 10-28 days, the initial steroid dose is usually reduced by 25%. The dose is generally given for another 10 - 28 days and depending on the dog’s progress and clinical signs the dose is significantly reduced once more for a further 10-28 days; and again in another 10-28 days. Anecdotal evidence has shown that if at this stage the dose is lowered more slowly, or reduced to an every other day dose over a period of months rather than weeks, relapse are less likely to occur.  It is always tempting to get your dog off steroids as soon as possible, but when treating autoimmune disease, as long as the dog is on a low, every other day dose then taking the last stage slowly seems to work best, depending, of course, on the severity of the disease and allowing for the difference in individual response - no two dogs reactions are exactly the same.  With some autoimmune diseases such as SLE, the dog is likely to be on steroids for the rest of his life. Usually an every other day dose can be achieved, but you risk a relapse if you take the dose too low. Below is the best example of a reducing immunosuppressive protocol I have come across. It is an excellent guide and can be adjusted to the individual.

Example: Reduction Protocol for prednisolone:

Clinical Immunology of the Dog & Cat , 2nd Edition,  by Michael J Day
Professor Michael DayBSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS 

Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.


This example is based on a dog receiving an induction dose of 1.0mg/kg/q 12hrs (q = every)
Dose                           Duration (based on clinical effect)
1.0mg/kg/q 12h                          10-28 days
0.75mg/kg/q 12h                       10-28 days
0.5mg/kg/q 12h                         10-28 days
0.25mg/kg/q 12h                        10-28 days
0.25mg/kg/q 24h                        10-28 days
0.25-0.5mg/kg EOD                    at least 21 days
0.25-0.5 mg/kg every third day      at least 21 days

Every reduction is made after consideration to improvement of clinical signs, blood results and side effects of the drugs.

Prednisolone:  "Doses above 2.2mg/kg/day do not give more immunosuppression but do cause more side effects. Many internists believe that prednisolone doses should not exceed 80mg per day, regardless of the dog's weight."  Plumb's Veterinary Drug Handbook Eight Edition.

How Do I Know if My Dog Will Relapse?
Until you have attempted to wean your dog off of the tablets for the first time you will not know if he is likely to relapse or not.  Sometimes during the weaning off process, before you even get down to an every other day dose, he may relapse.  If this happens then the drug dosage has to be raised, probably up to the last dose before the relapse (maybe a little higher, depending on the severity of the relapse) and then start the weaning process again.  If this happens again, then you and your vet may have to settle for keeping him on a low maintenance dose to achieve a good quality of life. A low, every other day maintenance dose of prednisolone is preferred to enable the dog’s liver to rest in between doses. There are many autoimmune diseases that carry a good, drug free prognosis.  The more common, serious autoimmune diseases that may not need long term steroid therapy are: primary immune-mediated polyarthritis, autoimmune haemolytic anaemia and thrombocytopenia. However, as previously stated, all dogs are different and it very much depends on the individual dog, the severity of the disease, the experience of the vet and the vigilance and compliance of its owner.
If a relapse occurs whilst the dog is still being treated then true remission has not been achieved.  If the dog has achieved remission and has enjoyed a period without drugs or is on EOD maintenance drugs, when a relapse occurs or he develops another autoimmune disease, he has encountered a ‘trigger factor’ which has induced this change.


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