Prednisone or prednisolone ?

Bones, joints and muscles
1

I have been reading Kate Gilbert’s book “PMR and GCA: a survival guide. As many of you who have read it and discussed on the forum before, this is a really excellent help for those of us who just started or who have been long suffering with these diseases.

One thing that I noted was that throughout the book she refers to our ‘famous’ corticosteroid as ‘Prednisolone’ – there was not one mention of Prednisone. I initially thought that this was a typo but apparently not.

I checked into it and read that the difference between prednisone and prednisolone is that one is the precursor to the other. Prednisone is activated by enzymes in the liver to turn into prednisolone. Apparently they do have similar uses but prednisolone is more readily absorbed by the body and is used when there is liver toxicity or liver failure involved.

This indeed surprised me as my rheumatologist has never mentioned or prescribed anything other than Prednisone.

It seems from researching the two names that they have many similarities, but there are differences. The chemical structure and molecular weight are different and prednisone is administered only orally, whereas prednisolone can be given orally, topically or injected.

Anyway, this has surprised me and I am now wondering if there is any information that all my “friends” on this forum can share with those of us who have not heard of this before.

And many thanks to you all for your constant helping and sharing with all of us who are ‘laden’ with PMR.

David

2

Very interesting.  I, too, always thought it was a spelling thing.  Will read the article.

Constance

3

David, those of us in the UK are prescribed Prednisolone whilst it seems those across the pond take Prednisone.  I have always liked to think, rightly or wrongly, that with Prednisolone not having to be activated by the liver in the same way as Prednisone, that Prednisolone is the lesser of the two evils!  Eileen will have the best medical resources at her fingertips and will, I am sure, give you themost informative answer. 

4

I live in Denmark and here also it is Prednisolone that is prescribed.

I seem to remember reading on this forum the explanation of the difference between the two and it is the same explanation as the one you have read.

5

Which is used tends to some extent to be traditional and what has always been used. In the UK it is almost always prednisolone that is used as it saves the liver a bit of strain and it acts very slightly faster. In the USA it is often prednisone or methyl prednisolone (Medrol) - which has a methyl group added to the structure and is supposedly more effective. They are all medium-acting corticosteroids - the effect lasts between 12 and 36 hours so require a single dose per day for the majority of patients. Hydrocortisone does the same thing - but you would need 3 doses a day. There are others where the effect lasts longer - so you would either have an increasing effect if you took it daily or you would take it every few days. Once daily dosing is the simplest for patients to get good compliance - without which no drug will work.

I have been on all of them: prednisolone in the UK at the start, was switched to Medrol here in Italy and experienced horrible side effects - in fact all it did was give me side effects! Massive weight gain, my skin and hair went mad and I developed a superb dark beard - but the anti-inflammatory effect was non-existent. It allowed a massive flare and I was switched to Lodotra, the only other form of medium acting corticosteroid available here, which is prednisone. NO side effects with it at all for me - unless you count allowing successful weight loss!

6

mine is called prednisolone

7

Hi David,  book sounds interesting. I'll google it.  Also my GP explained the difference to me...I'm taking predinsolone...  

  We need to ask questions ....they may not like it but we MUST.  Dr's are not infallible ... I sent the article to the Rheum. And he called and thanked me and apologized...however I will not return to him.  I lost my trust in his decisions...

take care

8

Hi David,

Thank you for bringing this to the attention of those of us that didn't know the difference.  I thought prednisolone was just what they called it "on the other side of the pond" as Eileen calls it (I live in Canada). I also wasn't aware of the differences between Medrol and Lodotra and prednisone either so thank you for that Eileen.

For anyone that is already taking other meds or does have liver issues this could be quite important I think.  Will definitely check with my Rhuemy when I seem him next month.

Diana🌸

9

When I saw my rheumy two weeks ago, and told....you must come off those steroids!  She then said, if you have a flare up, we could try you on something else...well I`ve seen what Methotrexate has done to my sister....no way to that one!..so, my question is, what else is there, do you know....is Lodotra, available here in uk?  Thank You...

10

Lodotra is only available in the UK on the NHS for rheumatoid arthritis and I know of 2 people with PMR who get it privately - which means paying for it and it is not cheap, about £75 per month. It is still a corticosteroid with all the same risks of the side effects - I'm probably just very lucky in having none at all, I didn't have many with prednisolone either.

I'm sorry - I don't know where these rheumies get the ideas from. The only guaranteed successful drug for managing PMR and GCA is prednisolone so what is your rheumy suggesting trying you on? The reveiw articles all say the same: the mainstay of treatment for PMR and GCA is prednisolone.

There is a trial ongoing at the moment with toxcilizumab for GCA and it is also intended to try it for PMR but it isn't instead of pred, it is to see if using it can get patients off pred faster so you take both and the idea is to see if the taper will be quicker with fewer relapses/flares. There was a very promising trial in Southend using leflunomide a few years ago where they claimed that 22 out of 23 patients went into remission. However, I know a few people who were put on leflunomide and it either did nothing or made them ill and they had to stop taking it.

Some people have been put onto methotrexate or azathioprine - the results are mixed. Some have reduced their dose of pred to start with but then later had flares and been back on higher doses of pred. The medical literature has 3 studies, one said it worked, one said it didn't, one didn't know. Which is hardly convincing to me - so if you are put on them it is your rheumatologist doing research on you IMHO without the close monitoring that is guaranteed in a clinical trial.

I do know a couple of people on the forums who find that methotrexate or azathioprine do help - they are still on pred though. The only way to find out is to try I'm afraid.

11

Hi Eileen,

I took prednisone for a period of about 4 months after my initial start of PMR – starting at 20 mg and stepping down to 9 mg. Then I assume that was too rapid as the first ‘flare’ happened and pain levels zoomed up.

My rheumatologist reviewed my multi-blood test series (lots of them as they are covered by my US insurance) and determined that I would need to increase prednisone back to 20 mg but start right away on a very slow taper when my ESR dropped from the 60 level to approximately 30.

Also she put me on methotrexate (a slowish step up from 5 mg to 25mg/week) with the intent that I would stay at 25mg/week for the entire time that my prednisone taper was actively being reduced down to zero. She evaluated that some of my symptoms were from relatively long term steroid use rather than just the PMR and that methotrexate would assist me in maintaining a long taper to zero without too much pain. I have a fairly high pain threshold (determined by doctor’s testing for another issue) and figured that I would give it a try.

I had heard all the side effects, that as with all drugs is a longer list than the benefits! You may lose your hair, develop mouth users and feel sick all the time, etc. etc.. AND worse of all – you can’t drink alcohol, -OH NO !!

My conversation with another patient who was on methotrexate was very encouraging – so I started - and took my weekly tablet of folic acid (1 mg) along with my weekly alendronate sodium (70 mg) to prevent all those other nasty things from happening.

I initially started taking my full pred dose early in the morning but found that as the taper got to about 10 mg, I was having bad mornings – so during the 10 mg level, I did try a 1 month trial of Delayed Release Prednisone (Rayos) to see if I could balance the distribution. I personally would not recommend the delayed release as I had a lot more pain. However, my rheumatologist did suggest that using regular prednisone I could make my own dose time adjustments for pain balance – so I did start an approximate 90% am – 10% pm schedule and this has worked well for me.

Also when nighttime (1am -3am) pain bothered me, my rheumatologist did allow me to take a very low amount of Ambien (zolpidem tartrate) – I would cut the 5 mg pills into halves and quarters (a very low level) and this tiny dose would have a huge change on my sleeping through the night if I took it at about 11pm.

Anyway, I have been tapering prednisone approximately 1 mg per month and still taking 25 mg of methotrexate per week – it is now 11 months since I started with the methotrexate and I am just about to hit the 4 mg pred level and all is going relatively well. Most of my joint muscle aches (shoulder, thigh, etc.) are at a relatively low background level – the only bad issue is hand joint pain.

C-reactive protein and ESR test results are now into the normal zone and I pay a bit more to keep on checking these, glucose and other liver related blood levels – keeping my fingers crossed !

Eileen - I have been so helped by your knowledge during my 15 months of PMR  - so, the purpose of this long California story of a British man was to give you some idea of how one of “your” methotrexate patients has handled the drug that does not have any really good research – and like everyone else on this forum – I’ll keep you up to date on my 4 to zero mg pred taper with methotrexate ‘side kick’. Thanks as always for ‘your’ brain.

12

Thankyou - I do like to hear the good bits too.

It's Rayos I'm on - Lodotra in Europe - and I think it is brilliant. Don't quite understand what you mean by "balance the distribution" - I take the entire dose at 10pm, it releases in a single shot at 2am and the peak pred level is achieved by soon after 4am, which is the idea. No morning stiffness, lasts all day, and as far as I can tell, no side effects for me. 

13

Thank you very much for this info!!  I do suspect it will be Methotrexate that my Rheumy hinted at....my sister was extremely ill for 3 weeks, after taking just two 15mg doses, which scared me....and she can tolerate medication far better than me...my Rheumy agrees having Fibomyalgia as well, makes things more difficult....I will stick with things as they are (hopefully) 

I have lessened the blurrred vision/ balance, by splitting the dose (14mg) and can at least leave the house!...It seems I can`t take the hit all at once!....Once again, thanks for explaining this to me....

14

Hi David - thanks for the methotrexate experiences. Your pred and tapering sounds very similar to mine. I was started on metotrexate a couple of years ago now, to help ge my prednisolone levels down - am now down to 10 mg pred and recently started on injecting my 20 mg weekly mtx I think that my rheumy is getting slightly concerned that I am not responding to my meds as I should. I am also on alendronic acid as I suffer from osteoporosis.

So just to say thanks for your mtx update - good to hear from someone who is taking it.

15

Ps,  Hope your granddaughter is improving!.....

16

Hi Eileen,

What I meant about “balance the distribution” was that I thought that the increase in pain may be due to my absorption rate not being quite normal and the distribution effect of the corticosteroid needed to be modified.

That’s why my rheumatologist and I thought that the Rayos (Lodotra on the other side of the pond !!) may be appropriate.

Knowing that the maximum activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight, exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity.

As you mention, Rayos releases the active prednisone approximately 4 hours after intake.

My rheumatologist said that Rayos was required to be taken at an equivalent dose as the immediate release prednisone that I was taking and continue to be taken at that dose. If after a reasonable time there was a lack of satisfactory clinical response, she recommended that the Rayos should be discontinued and that I should be transferred back to the prior immediate release prednisone.

So I started the 1 month trial, taking the Rayos at about 10-11 pm and within a few days my pain level increased substantially – mainly starting pain increase at about 4-5 pm and not reducing until early morning. There were a few variations on the maximum pain times during this trial but there was obviously something that was not right about my reaction to the ‘time release’ of Rayos.

Checking into the format of Rayos, the core tablet of prednisone is in an inactive shell that supposedly delays the onset of the prednisone by about 4 hours. This causes a delay in the time until peak plasma concentration is achieved. Apparently the mean time for healthy male subjects is 6-7 hours compared to 2 hours for immediate release prednisone. I read that the peak plasma concentrations are comparable for Rayos and immediate release prednisone after a light meal – about 2-3 hours. But I also understand that absorption rates of Rayos can be very much affected by the content and time taken after intake of foods of differing types. I did try a few different issues related to this potential – but no luck.

So anyway, I went back to immediate release prednisone - taking 8mg in the morning and 2 mg after supper and things improved dramatically.

Who knows how the body works – but that’s my story about Rayos.

David

17

I've just read the pharmacokinetic study - no mention of gender-related effects, just that 6-7% don't absorb it normally. You weren't confusing the DR format of Rayos with the enteric coated version of pred where it takes about 6-7 hours for absorption?

Whatever - I hope you and your doc have submitted a yellow card report. 

18

It was a while ago, but I believe that the 'male' enumeration was from the Rayos pharmacokinetic documents - but anyway I guess that I'm in the 6-7% bunch !

Maybe that's why I am having some success in pain reduction by distributing regular IR pred in varying %'s for my AM and PM doses - depending on the mg level that I am taking for my taper. Maybe my maximum and minimum activities of the adrenal cortex are slightly different ranges than normally assumed by rheumatologists and conventional pred dose expectation.

Have you researched anything related to this aspect of the efficiency of corticosteroids related to the adrenal cortex activity ranges and how it is possible to determine the adrenal cortex activity ranges in individual PMR patients so that more precise dose times could be identified to help patients ?

David

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PS - we don't have a Yellow card system in the US - unfortunately - and I don't think that a US doctor would submit to the UK one.

If you do that sort of 'criticism' here in the US - you get a law suit instead of medal !!

20

David, I would be surprised if the US didn't have a similar reporting scheme on adverse effects with different medicines similar to our Yellow Card system here in the UK.   What about  the MedWatch scheme: The FDA Safety Information and Adverse Event Reporting Programme for instance?