Weight based dosing of Azathioprine and 6-MP

[David]

I have been reading about how some doctors are working to optimize dosages of 6-MP and Azathioprine. In papers such as this one, they state:

The therapeutic efficacy of 6-MP or AZA are correlated with 6-TGN levels between 235-450 pmol/8 × 108 erythrocytes. Because several studies have shown that weight-based dosing is poorly correlated with 6-TGN levels, monitoring thiopurine metabolite levels can help optimize immunomodulatory therapy while minimizing adverse effects.

What they're saying is that one of the "metabolites" of Azathioprine and 6-MP, 6-TGN, is shown to be what causes the beneficial aspect of these medications. If your blood level of 6-TGN is between the number above, then the medication has a good chance of working. If it's lower, it's probably not going to work (so an increase in dosage may be warranted), if it's higher, you're at increased risk of [wiki]myelosuppression[/wiki] so a lower dose may be called for. They also feel that 6-TGN levels don't correlate well with the normal way 6-MP and AZA are dosed: by weight.

Point being, it may be a good idea to discuss the idea of monitoring your 6-TGN levels (and 6-MMP for that matter) with your doctor if that's not already being done. And if you haven't yet started Azathioprine or 6-MP, you may want to discuss the idea of having your TPMT enzyme levels or genetic tested first as that can also help optimize dosing.

I hope this helps someone

 

[Chuck78]

My dr just switched me from Humira to Aza. She's having me do lab work every couple weeks until we get the proper dosage. Thanks for posting this, at least I feel like the lab work is worthwhile.

 

[MelissaM24]

I get my levels checked, but I hadn't done my lab work for a long time because a lot of the labs around my area don't know how to do the blood work for these tests as they have to be sent to a lab far away from where I live and refrigerated, etc. so I have to go to a certain lab and don't have a lot of energy to get over there. So glad I got it done yesterday though.

 

[skywench]

I'm on Azathioprine but my biggest struggle is the prometheus test. My insurance only pays $35 of the lab bill which usually runs $250 or so. I swear, having a chronic illness costs a small fortune. Even with insurance.

 

[David]

skywench, which specific prometheus test is that?

And yes, I feel your pain about the financial hardship

 

[skywench]

I've blocked it from my brain but if I remember correctly one was the PROMETHEUS TPMT Enzyme to determine how much dosage to start me on and the other is PROMETHEUS Thiopurine Metabolites which the doc would like me to do every 3 - 6 months at $250 a pop out of pocket. Ouch!

 

[David]

skywench, do you think this might help?

 

[skywench]

That's exactly what I submitted to my insurance after they denied the claim altogether because I didn't use a "network" lab. After they received that letter was when they agreed to a whopping $35 reimbursement. I then took it to a second level appeal which was denied, also.

Last week, I submitted my third and final appeal so keep your fingers crossed. My company self insures but BCBS administers and they're the ones that denied the first two times. This final appeal actually goes to my company's HR and they have some board that looks at all the paperwork. I sent them a small book of documentation so I'm not going down without a fight!

 

[MelissaM24]

I definitely know the crazy financial aspect of having Crohn's/IBD... it's crazy. I have good insurance, but it is expensive. And I also have Medicare now because I have SSDI even though I'm only 25. You would think that my premiums for my other insurance would go down with them knowing that Medicare is primary and going to pay 80% of the bill, but nope! It just keeps going up and up and up every year! We have an insane amount of medical bills, my husband and I. And we're just a young married couple! But we just have to trust the God will provide.

 

[David]

skywench,

It's all about the $$$ for the insurance companies. Can you amend your final appeal? I just remembered the paper I linked in the first post had this:

Studies have found that checking TMPT activity may be cost-effective as compared to standard therapeutic dose administration[33,41]. Traditionally, AZA or 6-MP was started at a low dose and progressively titrated up because of safety concerns (bone marrow suppression, hepatotoxicity, etc.). Using this strategy, time to initial response is delayed and can take up to 6 mo to reach therapeutic response[6,33,42,43]. Compared to traditional thiopurine dosing, monitoring TMPT can allow faster achievement of initial response (22.4 wk vs 18.9 wk) and lower costs at 1 year ($7142 vs $3861)[33]. Thus, patients found to have normal TPMT could have dose escalation sooner therefore avoiding delay in achieving response[33]. The cost-effectiveness of measuring TPMT activity was independently shown in a separate study[41]. Furthermore, awareness of TMPT activity can help to avoid potential deleterious consequences of thiopurine therapy. For example, in patients with low TPMT activity, a lower initiation dose or avoidance of either 6-MP or AZA is recommended due to risks of leukopenia[16,44]. Albeit, TMPT activity monitoring is not universally available to all practitioners; in these cases, thiopurine may be started at a low-dose (50 mg daily) and titrated up with weekly monitoring of CBC and liver function tests during the first 2 mo, and once every 3 mo thereafter[20].

Now, this isn't TMPT specifically but it's really close and could be argued as such.

 

[dreamintwilight]

I had been on azathioprine for about a year on 75mg. Before starting it, my doc ordered the TPMT Enzyme test to make sure I could metabolize this drug properly and I got the green light. Last fall he had me get the test again to check my drug levels because I had mentioned the possibility that we might start a family in the near future. I didn't quite understand the necessity of having it again, but the results came back that my levels were low and he upped my dosage to 100mg now. Prior to the increased dosage, my Crohn's was behaving for the most part, but I would get some occurrences of bloating here and there that were annoying.

I can say that those occurrences have decreased isgnificantly since I started taking the 100mg. So, kudos to my doc for having me repeat the TPMT test and adjusting my dosage accordingly. It makes a lot of sense.

 

[DustyKat]

Hey Marisa,

Just saw your other post about the backorder and using generic Imuran. In view of the above post thought you might be interested to read this study...

http://www.crohnsforum.com/showthread.php?t=30340

Dusty.

 

[dreamintwilight]

Thanks, Dusty. It doesn't surprise me to read of the difference between generics and branded formulas of a drug just because I've heard things in the past about how some patients are more sensitive to generics than brands (not Crohn's-specific).

I wonder if there is a price difference with the Imuran prescription as opposed to the generic azathioprine. If there is a difference, then I don't mind so much that I am taking a generic as long as my levels are monitored properly!

 

[Irene3]

Thanks for this David! Funny thing is, I never had this tested. Started on 100mg of aza, stoped taking it because of side effects, then my gi wanted me on 150. Then after going into hospital mid last year, 200mg. I took aza for a few months, but then 5 min in the sun even, became horrible. I'd go bright red and feel like I was burning. Could this have something to do with that. Because 6mp is a lot better, though I still have a little light sensitivity, but nothing compared to aza. And it may still be because of it- but I'm only on 100mg of 6mp.
Shouldn't this automatically be tested, when doubling a dose of aza or 6mp... If it was prescribed by weight in the first place?
Good to know either way, so thanks!

 

[DustyKat]

Our prescriptions are subsidised in Oz so the price is capped if it is on the PBS, I think the generic and the brand are the same price through the PBS. There would be a difference of about 20+ dollars per 100 50mg tablets if it wasn't on the PBS.

Dusty. xxx

 

[David]

I took aza for a few months, but then 5 min in the sun even, became horrible. I'd go bright red and feel like I was burning. Could this have something to do with that. Because 6mp is a lot better, though I still have a little light sensitivity, but nothing compared to aza.

Sun sensitivity is a known and common side effect of Azathioprine. I would have hoped someone would have told you about that

Shouldn't this automatically be tested, when doubling a dose of aza or 6mp... If it was prescribed by weight in the first place?

It's easy for me to say it should be automatically be tested because it's logical but doctors no doubt have to take more into account. For example, I'm sure a person's insurance/financial situation is a variable. There may be other reasons not to do it, but I can't think of any.

 

[MelissaM24]

Does anyone know which is better, Azathioprine or 6mp? My Dr. put me on Aza. a few years back and my levels were low, so he upped it. Then my levels were too high so he lowered it back down, but added Allopurinol along with it to up the therapeutic benefits without upping the bad parts.

Anyway, I have never noticed a difference being on it. I am also now on Humira weekly (Remicade never helped enough), low dose pred. (still trying to get off that last bit from my last huge flare), and Entocort. I was wondering if I should ask my Dr. to try switching to 6mp, even though he told me it's the same drug, just metabolized differently. Has anyone had success with one of these but not the other?

 

[Johnnysmom]

Melissa, My son is on 6 mp and had the same issues and his dose was lowered and allopurinol was added. My guess is you would need allopurinol on 6mp too. Also my son has been on 6mp for 8 months and just this month did his blood work show he is in the theraputic range so it can take a while to get it right but I so appreciate my son's G.I.'s diligence on this.

 

[NZ1]

Hi,
I have UC and had very successfully treated it with 150mg/day of azathroprine for 5 years, until 2 years ago when it started to have mild to moderate flares and was never in full remission. My gastro has just worked out why, some people who are deemed as non-responders or who become this way may be metabolising azthroprine through a different pathway, the ‘shunters’, in short it stops working and like me they flare up. Recent research has shown that using a new drug, allopurinol, can then force azathroprine to work correctly, I’m trying this now and it seems to be working after a few weeks, although probably need to wait a few months to be sure. Google azathroprine, allopurinol and shunters for info since I can't post a link.

 

[David]

NZ1,

Did your doctor reduce your dose of Azathioprine when he put you on the Allopurinol?

 

[NZ1]

Yes, trying 100mg/day and testing metabolites to see if that is the right level. I'm male and 190lb.

 

[David]

This and this might be of interest for you.

Welcome to the community by the way