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6mp and sub therapeutic Thiopurine Metabolite levels

My son has been on 6mp for a year and a half. His dose started at 50 mg and has been adjusted almost constantly since he started. He started to have very high 6-MMPN and 6-TGN levels about 3 months after starting 6mp and his dose was cut in half and the Dr. added Allopurinol. Long story short, we are now back to the 50 mg dose we started at. He is doing well physically, labs are great, and Fecal cal is normal (64) after being 586 in July. He really couldn't be doing any better. But his last blood draw showed his 6mp level is sub therapeutic. The Dr. gave us the option of staying on the 50mg dose and having Johnny in the sub therapeutic range or raising the dose to alternating 50/75mg dose. This could land us back where we were with the risk of Leucopenia and Hepatotoxicity. The Dr. left it up to us to decide.

So my question is, has anyone had long term success at a sub therapeutic level of 6mp? Or should we try the higher dose?

His labs numbers are:

6-TNG 6-MMPN Dose

1/11/12 586 6968 50mg

2/17/12 606 2025 25mg

3/23/12 292 758 25mg

4/23/12 211 769

5/30/12 377 891

7/02/12 266 1016

11/26/12 206 757 37mg

1/22/13 130 739 37mg

2/25/13 161 2190 50mg

4/15/13 134 1524 50mg

6-TGN reference range 230-400
6-MMPN reference range <5700

The GI said he had no explanation why the 50mg dose effected him so much before and now it does not. I did tell him that when Johnny was first diagnosed our old GI gave us strict instructions about taking the 6mp. No food or milk products one hour before or two hours after. Once we moved to Cincinnati our GI said that we did not need to follow that regimen. We stopped being careful about it around December 2012. His GI just nods his head when I talk to him about this. He doesn't feel the two are related.
I have no answer for you but am very interested to see what others say. The thing I always throw at our doctor is, "If this was your child, what would you do and why?"

Is your intuition pulling you in any direction? When are the next labs?

my little penguin

Staff member
DS was on 6-mp for about 8 months.
He had similar problems like your son -
he was sub therapeutic for a while so we increased only to
get high numbers ( liver) at first then alarming number.
DS was decreased and allopurinol was added.
He went from 50 mg
to 12.5 mg of 6-mp with allopurinol.
This again left him sub-therapuetic .
We increased to 25 mg 6-mp and this was too much again for his liver.

WE discussed the every other day dose idea with our GI.
He was against this for DS for two reasons:
1.) you are under treating and over treating constantly with you keep switching doses so the blood levels are not normalized.
2.) on the HIGH dose days you are still affecting the liver even if your overall numbers are not as bad.

The sub-therapeutic levels for DS at least left him with ongoing inflammation in his TI and new inflammation in his sigmoid/rectum.
WE did not "know" this by blood work OR by fecal ( his was 80 at the time)
the only thing that showed this was scope.

I would put it back on the doc as well.
ASk what do you see happening if we do nothing, risks for change and what do you recommend.
sometimes wording the question right gets their recommendations.

Good luck
I agree with MLP. This needs to be the docs call - he has the experience to guide him on what is the most likely best outcome.

And I would note that you don't have to go up by 25 mg. There is the option of going up by 12.5 mg daily instead. It's a pain but worth considering.

Here's an interesting article by a top Mayo CD doc/researcher discussing the use of 6-MP vs. AZA in clinical practice. I believe his observations are all related to adult patients but his recommendations may still be valid or worth discussing with your GI.

The article underscores a second point I was going to make - that it might be worth trying a different drug (i.e. Imuran vs. AZA vs 6-MP) to see if you get a better result.


Finally, you may find this memory aid useful in your discussion with the doc:

B - what are the Benefits of this treatment
R - what are the Risks of this treatment
A - what are the Alternatives to this treatment
N - what happens if we do Nothing or what will trigger us to stop doing Nothing
D - Decide

my little penguin

Staff member
One last thing to consider
We found docs typically don't mention a possible med change
If they feel the current meds are doing the job.
At least for our son.
I think you need a long talk with the doc even if its just by phone.
Thank you for all the great input! It really has helped me to figure this out. I am uncomfortable continuing at sub therapeutic levels. I would definitely be willing to do 50mg + the 12.5mg daily dose. (Thank you Patricia!!) I think it would actually be easier than the 50mg/75mg alternating dose because we have done alternating doses before and inevitably we get mixed up on the days. So cutting the 6mp tablet isn't a big deal really. I like the idea of having the dosing more consistent too. (Thank you MLP for that) It sounds like our DS's response to 6mp has been very similar.

Thank you David for the article. I am amazed once again!! I will print it up for my GI and see what his thoughts are. It's worth giving it a try, especially before we give up the 6mp.

Catherine- He has gained a lot of weight since he started 6mp. I brought this up to the GI too and he said it would have nothing to do with his levels. (I still don't see how this could be, but I do believe him). He said it had to do with his TMP levels and how he metabolized 6mp rather than how much he weighed.

I knew you guys would give me some great information and clarity on this. Thank you all so much!
Our GI said the same thing on the TPMT levels too. Initially we are starting with a weight based dosage because you have to start somewhere, but after that it's more about how his body is handling the drug, not weight.

I hope you find a solution that works for him. Good luck!