Introduction

Started by dalebrook.bp@gmail.com, June 09, 2018, 12:54:02 AM

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dalebrook.bp@gmail.com

Hello - Thank you for the add.  I have a working cocker spaniel, Sophie, who was diagnosed with IMHA in late July 2017, went into remission mid December 2017, but then had a relapse on 28 December 2017.  She had a blood transfusion (dog to dog) and was able to come home the following day.  She was put onto 30 mg of Prednisone which has now been reduce in stages to 20 mg per day.  Unfortunately she had a very bad reaction to Azathioprine (in late 2017) which sent her liver enzymes up hugely, and we have just started her about a month ago on Leflunomide.  Her bloods are looking ok, although liver enzymes have gone up slightly, and we have now started a 25% reduction in Prednisone.  Hoping that this will be ok for her.  She is good in herself, ravenous (of course) drinks a lot, but I think her bladder has expanded in size (!!!) as she has to go out regularly but manages to go though the night without having to go out.  Absolutely exhausted emotionally (me not Sophie) but hoping things will progress well from here.  I live in Hamilton in the North Island of New Zealand.

Jo CIMDA

Hello and welcome

I am sorry your Sophie has IMHA.  I presume by now her HCT/PCV is within normal limits or thereabouts?  Hopefully with the addition of leflunomide you will be able to reduce the prednisolone quicker, and as you do these symptoms of drug induced Cushing's will start to fade away.  From your post it seems the most problems she is having is due to the preds. 

Hopefully this time Sophie will be in remission.  Limit any potential trigger factors such as vaccinations, chemicals, spot -on preventative treatments etc........ and take a look at the preservatives in her food and if there is anything that has the potential to be a trigger, look for a more natural food.  I hope this will be long term remission.  Some dogs relapse and then second time around they reach remission and it never occurs again. 

I you do have to return to an immunosuppressive drug treatment then check out the Michael J Day immunosuppressive drug protocol in the files.  It is the best I have come across and it can be confidently used as a guide.  Prof Day is among the world's top veterinary immunologists.

Emotionally exhausting?  Yes, it is. Thank goodness Sophie is not aware of how mentally traumatic it can be.  It is a steep learning curve for sure.

Fingers crossed this time around will work.

Jo

dalebrook.bp@gmail.com

Hello Jo - thanks for your reply.  Her PCV is good - 38 and has been since early March.  The only real potential problem is the liver results - Alk Phos is 103, ALT is 236, AST is 63 and CPK is 511, so hoping they don't go any higher on the Leflunomide.  We have reduced pred by 25% each day (15 mg per day down from 20 mg), rather than doing every other day, as she didn't react very well to being on it every other day just before she relapsed in December - you could tell the difference between the days.  And also are doing 25% reduction only, as we did 50%  just before she relapsed and wanted to take things more slowly as she has been on the pred for so long.  She is on 1 capsule of milk thistle each day plus losec and low dose aspirin.

Have you any thoughts about Leflunomide - it doesn't seem to have been used much in NZ, but Sophie had such a bad reaction to Azathioprine - Alk phos went up to 3345 and ALT to 1458 at one stage.  One option would have been Atopica, but the cost would have been $500 per month in NZ which was just beyond us.  She is on Applaws grain free food - I think it is a UK food (manufactured in Australia), and had a very good rating on the UK site that grades foods (4.8/5).  I will check out Michael Day's protocol. 

Thanks so much.

Patricia

Jo CIMDA

Hello Patricia

It all sounds pretty good.  I prefer the preds to be brought to a low dose before going to every other day.  I think a better more stable effect is achieved by doing it slowly, but of course it all depends on how the dog is coping with the side effects of the steroids.    Sophie's current  liver results are OK at this stage and as you lower the preds they will get even better.  Also, as you further lower the preds the  PCV should rise because long term high doses of preds can suppress bone marrow production. 

I have known leflunomide to produce good immunosuppression, and also I have known it not to have had much effect.  It is certainly worth a try though, and if Aza wasn't tolerated then I think leflunomide  or mycophenolate would be my choice of combination drug.   Azathioprine doesn't suit all dogs, in fact  with all immunosuppressive drugs it is not one size fits all.  The most tolerated and effective immunosuppressive drug is prednisolone but if the regimen isn't carefully planned and tailored to the individual dog, the side effects can become become problematic. 

Milk thistle, Losec and low dose of Aspirin is all good but Sophie may not need the Aspirin now because the dose of preds is much lower.  You can ask your vet about this.  Applaws looks a good food.

I hope you will see a good result to leflunomide and you can continue to reduce those preds.
Jo




Winstedt-School

Hi there,

I have two small dogs. I love them very much and I can not imagine life without them. They bring a lot of joy into my world. And also have a positive impact on the development of my daughter :)

dalebrook.bp@gmail.com

Hello Jo

Not great news from Sophie's latest bloods, liver enzymes continue to rise, and PCV has fallen from 38 (where it has been for a couple of months) to 31.  I have attached lates blood results.  Sophie is under a vet who has been her main carer, who is a surgical specialist but has experience with IMHA dogs, and a medical specialist that visits Hamilton from Auckland each week.  It is the medical specialist who prescribed the Leflunomide, and when he saw these results he offered three options - to stay on the Leflunomide and drop the steroid, to stay on the steroid and drop the Leflunomide or try a new drug (Atopica).  We have been quoted $NZ500 per month for the Atopica, which is out of reach for us (Sophie has been ill for 11 months and we have already spent about NZ$13,000), which leaves the other two options.  After much discussion with her regular vet, we are reducing the Prednisone from 15 mg per day to 10 mg per day, and keeping the Leflunomide dose the same as it was.  I am a little unhappy with putting the steroid down when her PCV is going down, although her vet said 'There are no cell fragments etc indicating RBC damage occurring so I think we should be safe - there is always some risk with any medication change, but I think it is important that we try to reverse the concurrent liver issues'.  We agreed to redo bloods in two weeks or sooner if there is any change in her.  I wonder what you think about all this.  I am concerned about a relapse, as she had the relapse at Christmas and we were just getting on an even keel.. Not sure what result we might get if we phased out the Leflunomide, and how we would do that.  She is currently on 30 mg Leflunomide once daily.  Thanks for your help.  I can't fit the results files on as they are too large - is there another way I can send them?  Thanks

dalebrook.bp@gmail.com

Sophie's Biochem results 25.06.18:
Sodium 150, Potassium 4.3, NaK ratio 34.9, Chloride 109, Creatinine 76, Urea 4.9, Phosphate 1.60, Cholesterol 5.2, Total protein 66, Albumin 33, Globulin 33, A/G ratio 1.00, Calcium 2.54, Bilirubin less than 2.5, Alk Phos 181, ALT 319, AST 62, CPK 401, Amylase 371.

Haem results 25.06.18:
RBC 5.02, HCT/PCV 31, MCV 62, Abs Retic 70.28, Retic% 1.4, WBC 14.9, Neutrophils% 92, Neutrophils ABS 13.7, Lymphocytes% 4, Lymphocytes Abs 0.6, Monocytes % 1, Monocytes Abs 0.1, Eosinophils % 3, Eosinophils Abs 0.4.
Comment by Pathologist: The sample is lipaemic therefore RBC, manual PCV and MCV are the only vaoik RBC parameters.  Erythrocytes: Anisocytosis +       Leukocyte morphology appears normal.  Platelets clumped, platelet numbers normal.  *Thanks for sending a fresh film*     Saline agglutination test = Negative.   Veterinary comment: RBC parameters obviously trending down again with a non-regenerative response at this stage.  Ian, is this anaemia of 'chronic' disease?  Due to drugs?  Doesn't look like a haemolytic picture.  Leukogram suggests stress/response to steroids.

Jo CIMDA

Hi Patricia

I am sorry Sophie is not doing so well, but how is she in herself? 

The lab reports last comment is very interesting  'Ian, is this anaemia of 'chronic' disease?  Due to drugs?  Doesn't look like a haemolytic picture.  Leukogram suggests stress/response to steroids.'

Sometimes when high doses  of preds are used for a prolonged period it can suppress bone marrow production and it isn't until the preds are significantly lowered that the PCV starts to rise again, so reducing the pred is probably the way to go and see if the white cell readings (leucogram) and the PCV  improve.   High lever enzymes are to be expected when a dog has been on high doses of steroids for a while, and I would expect these to reduce as you lower the preds.  Personally, I wouldn't introduce another drug at this stage because as the lab commented the picture the bloods are showing isn't typical of immune destruction of the red blood cells.  These findings are common when long term, high doses of preds are used and when something is drug induced as you lower the drug things start to improve significantly.

When a dog has been on heavy medication and there are unusual clinical signs and blood results, the drugs have to be stripped back to reveal a truer picture.   Be positive if you can about this reduction in preds.  If Sophie's clinical signs allow then a slow reduction in preds might give a better chance of her reaching long term remission.  She is on Leflunomide so this should be sufficiently suppressing her immune system.  Immunosuppressive dose of leflunomide is:  3-4mg/kg/once daily  (Plumb's Veterinary Drug Handbook, 8th Edition)

I think these results could all be down to the preds.

Jo





dalebrook.bp@gmail.com

Thanks so much Jo.  Sophie is actually pretty good in herself, and your reply has eased my mind a lot.  I really appreciate your help.  Her Leflunomide dose is a little over 2mg/kilo - she is 13.5 kilos and is on 30 mg of Leflunomide once a day, and now 10 mg Prednisone once a day.  Still on milk thistle and low dose aspirin, plus Losec two weeks out of three.  Does this sound OK?

Patricia

Jo CIMDA

Hi Patricia

The regimen Sophie is on sounds very reasonable.  I hope as you lower the preds the PCV will rise. This is a common scenario.

https://www.drugs.com/sfx/leflunomide-side-effects.html

Also, according to the above link anaemia can occur in 1%-10% of human patients taking  leflunomide.  You can have a blood test to check the level of leflunomide in the blood.

You may just want to check with your vet the possibility of her having a gastric ulcer, although the Losec should have prevented this. What colour are her stools?

If she is good in herself, this is a good sign. 

Jo

dalebrook.bp@gmail.com

Thanks Jo.  There has been no sign of any blood in her stools - I usually check them every day - usually mid brown to slightly lighter brown, occasionally slightly darker, but I will make sure that I continue to check them.  I will mention about a gastric ulcer to her vet.  She has been on a stomach protectant right through, although lately she has been put onto two weeks on and a week off (not sure what the rationale for that is). 

Thanks again for your help.

Patricia

Riojadog

Hi

I've just found this forum after doing some initial research on IHMA. Our lovely 7 year old crossbreed Rioja, was diagnosed with IHMA only last week after going downhill very quickly.  In just 4 days we went from the vet thinking she had a urinary infection to her having a blood transfusion. She came home yesterday and it has been a rollercoaster ride for sure. Her count went down to 11 at its worst and is now around 18. To say this has been a huge shock is an understatement, there's so much information to take in. I would be really grateful for advice about what to ask our vet in these early days of Rioja's treatment and what we can do to help her through this really important time. It's heart breaking to see her so lethargic and listless with little appetite and this heat really isn't helping either, her body is under enough stress as it is.  Any pointers, helpful tips and advice would be so welcome as well as advice on how we can manage her condition longer term. I know the next few weeks are going to be crucial for her. Thanks all


Jo CIMDA

Quote from: dalebrook.bp@gmail.com on July 01, 2018, 08:09:52 AM
Thanks Jo.  There has been no sign of any blood in her stools - I usually check them every day - usually mid brown to slightly lighter brown, occasionally slightly darker, but I will make sure that I continue to check them.  I will mention about a gastric ulcer to her vet.  She has been on a stomach protectant right through, although lately she has been put onto two weeks on and a week off (not sure what the rationale for that is). 

Thanks again for your help.

Patricia


Hi Patricia

Two weeks on and a week off of taking a gastroprotectant is a new one on me, so I can't help there.  Omeprazole is usually only given for 8 weeks, so I don't know if that has anything to do with it.

Jo

Jo CIMDA

Quote from: Riojadog on July 02, 2018, 08:17:17 PM
Hi

I've just found this forum after doing some initial research on IHMA. Our lovely 7 year old crossbreed Rioja, was diagnosed with IHMA only last week after going downhill very quickly.  In just 4 days we went from the vet thinking she had a urinary infection to her having a blood transfusion. She came home yesterday and it has been a rollercoaster ride for sure. Her count went down to 11 at its worst and is now around 18. To say this has been a huge shock is an understatement, there's so much information to take in. I would be really grateful for advice about what to ask our vet in these early days of Rioja's treatment and what we can do to help her through this really important time. It's heart breaking to see her so lethargic and listless with little appetite and this heat really isn't helping either, her body is under enough stress as it is.  Any pointers, helpful tips and advice would be so welcome as well as advice on how we can manage her condition longer term. I know the next few weeks are going to be crucial for her. Thanks all

----------------------------

Hi and welcome

I am so sorry Rioja has IMHA.  The fact that her count has gone up to 18 following the blood transfusion is good but she needs to be on the correct dose of steroids to suppress the immune system significantly enough to stop the destruction of red blood cells.  Does she have regenerative (the immune destruction is within the circulation of the blood)  or non-regenerative (the immune destruction is targeting the precursor or immature red blood cells within the bone marrow) AIHA?  Below is some information about what to expect when treatment has started and the best drug protocol that I have come across.  You can compare it to the treatment Jioja is receiving.

I hope you see an improvement in her very soon.  You are right, the hot weather doesn't help at all.

Jo

Treatment for inflammatory/systemic Autoimmune Disease

Excluding autoimmune diseases where hormone replacement only is required, most of the diseases are treated by significantly suppressing the immune system in order to stop the destruction.  There are only a few exceptions to this.
The drugs most commonly used for the treatment of autoimmune/immune mediated disease are steroids (corticosteroids), such as prednisolone.  These may be used as the sole immunosuppressive agent or used in combination with cytotoxic drugs, such as Azathioprine. Cytotoxic drugs are used in human medicine to prevent the body rejecting transplanted organs. Many vets can be reluctant to use azathioprine with prednisolone as a combination therapy to treat autoimmune disease but there is certainly value in using a combined treatment as azathioprine increases immunosuppression and generally allows the steroids to be weaned down in the shortest possible time whilst maintaining a good level of immunosuppression.  It can make a huge difference to the outcome, and in some cases it makes remission more achievable.
All drugs have the potential to cause side effects and the major concern for treating animals with high doses of steroids and other potent drugs are the unacceptable side effects that may occur.  It is a fine balancing act between bringing the disease into remission and the side effects of the drugs.  All of the above drugs have the potential to cause a degree of liver toxicity but when the drugs are reduced the liver will recover. It has to be stated that without these life- saving drugs, in many cases, the dog would die, but the objective is to use the minimum dose to control the disease, for the minimum duration of time. However, the dose has to be 'immunosuppressive' eg.  Prednisolone 1-2mg/kg/every 12hrs usually starting at 1mg/kg/12hrs (Plumb's Veterinary Drug Handbook). If this dose does not produce the desired effect it can be raised. The action of prednisolone is rapid and at times it works like a 'miracle drug'.  Note: It should be given with food to minimise stomach irritation.
If the dose is too high the side effects may cause other major problems, if it is too low it will not control the disease or achieve remission.  One of the most common accounts are when a dog has been on immunosuppressive doses of prednisolone for too long and they start to display overwhelming signs of iatrogenic Cushing's syndrome (see below) and very often the clinical progress they have made in combating the disease has reached a plateau and the dog now appears to be weak, off their food and quite depressed. Prolonged, high doses of prednisolone can also cause bone marrow depression and the red blood cell count can decrease. These clinical signs can cause confusion for the vet and owner, and a relapse of the autoimmune disease is often suspected. It is not unusual for the steroids to be increased when in fact they should be decreased. 
Azathioprine is usually tolerated well, but as with all drugs individual dogs can be affected in different ways.  Side effects can include reduced bone marrow production, but this is rarely a problem unless the dog is kept on this drug for a long time. In contrast to prednisolone which has a rapid effect on the immune system, azathioprine takes at least 10 days to have some effect and approximately 4-6 weeks to reach its full potential. 
Note:  Azathioprine and all other cytotoxic drugs should be handled with extreme care. Cytotoxic drugs should not be handled by pregnant women.  Rubber gloves should be worn and the tablets should never be split or broken.
Atopica  (cyclosporine) is licensed for treatment of atopic dermatitis in the dog but it's increasingly being used as an immunosuppressant in 'combination' treatment with prednisolone and azathioprine for systemic autoimmune disease, despite the drug sheet stating   'It is not recommended to use other immunosuppressive agents concomitantly'.  I have known many dogs on this triple combination treatment that have eventually become overwhelmed by the side effects of the drugs and the outcome has been poor.  It may be worth, initially, trying a more simple approach to treatment, using immunosuppressive doses of prednisolone, before embarking on a 'prescription overkill' that may prove to be a difficult,  and an unnecessarily heavy drug regime for the dog. Human research suggests that Cyclosporin may also encourage abnormal cells to become cancerous and perhaps even grow more aggressively. Scientists are now looking for ways to block this tumour-promoting effect of Cyclosporin. (Clinical Pharmacology Made Incredibly Easy by Lippincott, Williams & Wilkins)
It must be accepted that sometimes these 'heavy' drugs have to be used, especially if the dog is not responding to treatment; and sometimes an additional drug can make all the difference to the recovery of the dog. In these cases the side effects have to be accepted as a 'trade off', in fact the dog may tolerate it very well.  However, there may be no need to prescribe combination drugs when there is a good chance that using immunosuppressive doses of steroids, and following the correct drug regime, may be all that is required to bring the disease under control.  The severity of the disease has to be taken into consideration when deciding on which combination drug regime to use, but more isn't necessarily best, and introducing one combination drug at a time would limit the side effects for the dog.
In addition to drugs used to suppress the immune system, preventative measures such as administering antibiotics to prevent infection, gastroprotectants to avoid stomach ulcers, and low dose Aspirin to minimise the risk of thromboembolism and DIC (disseminated intravascular coagulation) may be given. 
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.

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.

dalebrook.bp@gmail.com

Hello Jo

Sophie seems to be doing well on 10 mg per day prednisone and if bloods are ok next weeks looking at reducing dose - not sure how best to do it.  Vet suggested 10 mg one day and 5 mg the next day.  As Sophie didn't seem to respond well to the every other day dose that caused her relapse at Christmas, I am a bit iffy about doing different doses each day.  I would prefer 7.5 mg a day.  Do you have any suggestions about this?  Do you think the 5 mg one day and 10 mg the next day would work?  The only other drug she is on is the low dose aspirin.  Thanks for your help.

Patricia