Bobbi

[claricechin]

Bobbi was diagnosed with IMHA on 31 January and after taking several weeks of medicines her PCV has bounced back to 38 this week.

Medicine she's previously on:
Prednicare 5mg/tablet 1.5tablet twice a day
Famotidine 5mg twice a day
Clopidogrel 75mg 1/4 tablet per day
Aspen-imuran 25mg 1/2 tablet per day

The vet has decided to pause Bobbi's daily intake of famotidine for a week to avoid her stomach gets used to it.
But I'm a bit worried if it'll do any harm to her without the stomach protectant?

[Jo CIMDA]

Hi and welcome

I am sorry Bobbi has IMHA.  Looking at the dose of prednisolone,  I presume Bobbi is a small girl - how much does she weigh?  Has she been on the same dose of prednisolone since the beginning of treatment?

If Bobbi has been taking Famotidine since the beginning of treatment I wonder why your vet thinks it is upsetting her stomach?  If you are concerned then why not ask your vet to change to another gastroprotectant such as ranitidine?  One week without a gastroprotectant might not affect her, but who knows?

Imuran (azathioprine) tablets should not be divided, so I would also ask your vet about the safety of giving Bobbi a split tablet and ask if you should give a whole tablet every other day as opposed to splitting a tablet and giving a daily dose.

https://www.medicines.org.uk/emc/medicine/2882

6.6 Special precautions for disposal and other handling


Health professionals who handle Imuran Injection should follow guidelines for the handling of cytotoxic drugs (for example, the Royal Pharmaceutical Society of Great Britain Working Party Report on the Handling of Cytotoxic Drugs, 1983).

'Provided that the film-coating is intact, there is no risk in handling film-coated Imuran Tablets. Imuran Tablets should not be divided and, provided the coating is intact, no additional precautions are required when handling them'.
 

Jo

[claricechin]

Thanks Jo.

Sorry I should have given more details about Bobbi - she is a Shihchonpoo (Shih-poo x Bichon Frise) and will turn 1 year old next month.  She is gaining weight since two weeks ago and now she's 7.01kg. 

We are trying to control her diet but due to the side effect of steroid, she keeps asking for food the whole day (used to wake us up at 4am because she is too hungry  ) and now aside from her two main meals, we will fit in some snack time with some vegetables and little bit of meat. 

She has increased from 10mg to 15mg on her prednicare within the first few days when her PCV dropped from 23 to 18 and has been on the same dose since then until this week, it's reduced to 12.mg daily.

For Famotidine, the vet suggesting to give a one week break is that he worries the medicine will block/ stop the glands from releasing acid after prolonged intake of the medicine.  I wonder if giving Bobbi some natural herbs (e.g. slippery elm bark) would help easing her stomach or protecting her stomach?

It's interesting to learn about Imuran, I'll bring it up to the vet next time.  Meanwhile, there's a warning on the label that it needs to be handled with gloves.

[Jo CIMDA]

Hi

Bobbi is a little girl and smaller dogs cope much better with immunosuppressive doses of prednisolone, so that is good news.  Your vet is starting to reduce the dose now, which is necessary. Her appetite should reduce as the steroids are lowered but it is a common side effect.   For your information, below is the best reducing protocol for prednisolone that I have come across and it can be confidently used as a guide.  Prof Day is one of the world's leading veterinary Immunologists.

Slippery elm is a good herb that can heal the calm the digestive tract, but I have not heard of it being used as an alternative to a gastroprotectant during immunosuppressive therapy. As your vet is only withdrawing the famotidine for one week it may not have any lasting effect.  If Bobbi starts to show signs of upset tummy or bringing up bile then ask your vet to reconsider and either put her back on famotidine or put her on a different gastroprotectant.  Omeprazole is the most common gastroprotectant used with immunosuppressive therapy.

Jo


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.

The dose of azathioprine 2mg/kg/24 or 48 hrs, can be reduced initially by giving a lower dose tablet per day, or gradually reducing from daily dosing to every 2nd day, every 3rd day, every 4th day etc..... Remember, azathioprine tablets should not be broken or handled without gloves.

"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.

[claricechin]

Update on Bobbi
Her latest blood test result:
PCV 43.2
New red blood cell count 25

While we will restart reducing her Pred dosage (from 15mg to 12.5mg per day), I wonder if there's any concern on her new red blood cell count as it's sognificantly dropped from 120 last week?

Is it because the PCV is considerably high that would slow down the production of new red blood cells?

[Jo CIMDA]

Hi

  Fantastic!  A PVC of 43.2 -  that is within normal limits.

By the 'new red blood cell count'  I presume you mean the reticulocytes.  Yes, you are right.  As the red blood cell count within the circulation of the blood rises to within normal limits, production of reticulocytes will self regulate, and the numbers will continue to reduce until they are back to normal production eg., only producing enough reticulocytes to maintain normal PCV levels.  It is a circle - as the old red blood cells leave the body (usually around 100 days) new, immature red blood cells migrate from the bone marrow to the circulation of the blood, maintaining a constant level of red blood cells.

This is great news.  Many thanks of the update.

Jo

[claricechin]

Hi Jo,
Another update on Bobbi. She's her blood test this Monday with PVC 38. She is weaning off steroid by2.5 my/ day every three weeks. (Highest dosage 15mg now 7.5mg)
I wonder if there's any impact to speed up the wean off process , provided her PVC holds in satisfactory range, by every two weeks instead of three? 
Other than PVC, what are the other readings from blood test I should be aware of to ensure the weaning is on the right track?
Also, I've heard about fishing's, is the risk got higher the longer the steroid is being taken?

Thx,

[Jo CIMDA]

Hi

Bobbie's PCV has dropped a little and this might be because she has been on steroids for many months.  Can you just confirm that she is having 7.5mg pred a day?

The weaning process can be quicker but the decision to reduce has to be taken into consideration with how Bobbie is coping with the side effects of the steroids.  This is the drug induced Cushing's that you mention. See information about Cushing's below.

When the dose is being lowered the side effects of the drugs have to be monitored.  If you can get to 14 days before reducing the dose again,  that is fine but when you are at 14 days, if you look at the dog and see that it is coping with the side effects of the preds, then you might want to try to eek out the current dose to 14-16-18-21 days before reducing again.  It all depends on the individual dog, if the disease is being managed and in remission, and the side effects of the drugs.  No two dogs are exactly the same.

Ask if her liver enzymes are very high.  I would expect the preds to have cause them to be raised but it depends on how high. Also look at her clinical signs to see if the preds are causing symptoms that are intolerable for Bobbie.  Smaller dogs cope really well with the side effects, but 6 months is a long time if she is still on 7.5mg pred a day - but perhaps I have got this dose wrong.

Jo




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?[/b]
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.

[claricechin]

Thank you Jo.

Yes, Bobbi is taking 7.5mg/ day(3.75mg each in the morning and evening). She's on the current dosage since two weeks ago and we are due to take her for next blood test later this week for the next reduction.

The only noticeable side effect we've noticed is her big appetite and she has gained 2.5 kg since end of January when she's first diagnosed with IMHA. She's currently 7.8kg therefore we're concerned her over-weight would cause other health issues.

The last time Bobbi's liver enzyme was measured was six weeks ago. The vet only mentioned that her enzyme is high as expected as a result of the medication. But there's no previous reading taken so he couldn't comment on if it's a concern.

We are giving her milk thistle hopefully that's helping her liver though.

Could you please explain the 14-16-18-21 days strategy in more detail please?  Is my understanding below correct?
7.5mg/day —> 5mg/day : 14 days
5mg —> 2.5mg : 16 days
2.5mg —> 1.25 mg : 18 days

Or can it be from 2.5mg/ day —> 2.5 mg every other day : 18 days (?)

2.5 mg every other day —> every two days —> 21 days

Thanks again for your valuable advice.

[Jo CIMDA]

HI

I haven't explained this well.

If you look at the Michael J Day protocol you will see that at each reduction the dose of preds can be reduced anytime between 10-28 days.  This wide margin  of duration is to allow for the individual's response to the drug and the control of the AI disease, but also to monitor the side effects of the preds and if necessary (taking into consideration the presenting clinical signs and blood results) the preds should be lowered sooner rather than later.  So if possible the duration should be at least 10 days.  If the dog is coping with the side effects of the drugs then it is best if you can eek out that dose to 12 days.  If at 12 days the dog is doing well, and still no adverse effects of any concern, then eek it out further to 14 days, if all is ok then carry on with that dose for 16 days  and so on.......  When you reach 21 days if all is well then you can continue with the current dose to 28 days but anecdotally,  this is rarely necessary and a reduction of preds at anywhere between 10-21 days is a typical duration before reducing again. The dose and duration of steroids has to be tailored to the individual because all dogs are different and there is a huge contrast in tolerance between large and small dogs. 

Basically you must consider the side effects of the drug every day when a dog has been on significant doses of preds for a long time.   I hope that explains it a little better.  I am sorry for confusing you.  Please let me know if this is not clear.   

The side effects of the preds must be taken into consideration when treating with prednisolone.  It is a marvellous drug but some dogs don't cope well with very  high doses and for a long duration of time.   Some vets don't understand the principle of immunosuppressive treatment and they keep the dog on high doses for much longer than they need.  I have known some dogs to stay on very high doses because the vet thinks it is necessary.  This is not the principle of immunosuppressive therapy with prednisolone. 

Jo

[claricechin]

Hi Jo,
Thanks for your detailed explanation as always.
Another update on Bobbi's blood test result today:
PCV: 41 (close to her previous 'PB' of 42, yay!)
Liver enzyme readings -
ALT - 160 (was 455 - 6 weeks ago)
ALS - 116 (was 313 - 6 weeks ago)

We'll now reduce her pred dosage to 5 mg and take her back for next blood test in 2 weeks' time.

Could you advise if the liver enzyme readings are ok? 
Does the decrease of pred intake reduce her liver enzyme (I am assuming the lower the reading is better here)?

Thanks

[Jo CIMDA]

Hi

It all looks very good for Bobbi.  PCV of 41 is something to be happy about and I suspect it will continue to rise as you lower the preds too.

The liver enzymes are expected to be raised when a dog has been on preds for a long time.  As you lower the preds further they will continue to reduce.  When the preds are given every other day they might return to within normal limits, and when Bobbi is off the preds altogether they will definitely be back to normal. All the other signs of drug induced Cushing's will also reduce.

It is all going in the right direction and you can't ask for more.

Jo

[claricechin]

Hi Jo,
Bobbi has been on Aspen-Imuran 25mg (1/2 tablet per day) since February when she was first diagnosed with IMHA. Is it recommended to be reduce the dosage sooner or wait until she's completely weaned off the prednisone first? She is currently weighed 7.9kg (overweight)

She occasionally has runny poo.  Last Sunday she vomited twice and we took her to emergency vet. Had a blood test with PVC stays at 45 and some anti-nausea meds. Her symptom (nausea) seems have died down since Tuesday.

[Jo CIMDA]

Hi

Bobbi may have got  tummy bug which has caused the upset.  At least this is over now.  When a dog is on these immune suppressing tablets they are more vulnerable to infections etc. 

I am surprised Bobbi is still on prednisolone after all this time.  It is usual to wean off the pred and then start to wean off the Imuran.   Her PCV is very good so there comes a time when the pred (and other drugs) has to be weaned off altogether otherwise you will never know if true remission has been reached. 

You can wean pred off slowly by giving a low daily dose and then reduce to every other day dosing and then off altogether.  Then give Imuran every other day and then every third day etc.......until you leave it off altogether. 

Jo

[litex]

I am very sorry about what happened to your dog. It's been some time, so I hope it all ended well. Regards