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6MP and Incidence of Infections

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Posted 4/15/2014 12:07 AM (GMT -5)
I still have certain things to explore (especially regarding my stool analysis) before even considering 6MP, but i have been wondering as my new GI also wants me on this, as well as all my previous GIs. And this is the fifth GI i have seen in just 3 years!

My main concerns with 6 MP are:
- its potential to increase my risk of getting infections: for example i have heard of some people on 6MP whose sinus infections turned into double ear infections and pneumonia. This really worries me because I cannot take most antibiotics as they give me D, except doxycycline, so if i end up with crazy infections like these i will be in serious trouble
- its safety during pregnancy: in animal studies it's teratogenic but in humans it hasn't shown this potential, still i would not be comfortable taking it during pregnancy

So my questions are:
1. is 6MP's potential to cause serious infections related to the degree of suppression to the WCC (white cell count)? so if i get my bloods checked every month and make sure my WCC does not drop too low am i still at risk of these infections?
2. any evidence that 6MP can cause harm to the growing foetus?

Thank so much guys
Posted 4/15/2014 4:06 AM (GMT -5)
I've only been on azathioprine then 6mp for 3 months.

I have had recurring sore throats and a few low grade fevers but weirdly I didn't catch the cold that other members in my household had.

I'm on a very low does of 6MP because I couldn't tolerate higher doses - TPMT on the low side.
Posted 4/15/2014 7:11 AM (GMT -5)
I was on 6mp for about 6 years. Before I was placed on it, it seemed I was always sick. When I started on it, I actually got less sick than before. But when I did get sick, it got severe fast. I had regular blood work but it didn't prevent me from getting sick.

I don't know the answer to your second question. But I've seen women on HW who were on 6mp or Imuran and still had healthy babies.
Posted 4/15/2014 8:05 AM (GMT -5)
Conquer UC, then perhaps 6mp would help you and improve your quality of life. But of course with any medication there are risks. And you must weigh the benefit against the risk.

1. is 6MP's potential to cause serious infections related to the degree of suppression to the WCC (white cell count)? Yes, 6mp/Aza/Imuran works by lowering your white blood cell count. A little background, your immune system uses white blood cells (more specifically T-cells, one of three types of Lymphocytes) to attack infected tissue within the body, which causes inflammation, and kills infected/diseased cells. 6mp lowers your white blood cel count so less inflammation is caused in your large intestine but the effect of 6mp is systematic (meaning it effects your whole body and not just the intestine). While on 6mp, you will undergo regular blood tests. A CBC blood test counts the white blood cells present among other things and makes sure it doesn't get below a certain level. So if i get my bloods checked every month and make sure my WCC does not drop too low am i still at risk of these infections? Yes, even with monitoring your white blood cells are still decreased and therefore your body is less able to fight infections when they occur. That can mean an infection, cold, or flu lasts longer than normal. It can mean that you need to seek medicinal treatment sooner in the case of a UTI, bronchitis, or other such infection. Otherwise, those infections may spread or get worse much quicker than you'd otherwise expect.

2. any evidence that 6MP can cause harm to the growing foetus?

Pregnancy Category D

Mercaptopurine can cause fetal harm when administered to a pregnant woman. Women receiving mercaptopurine in the first trimester of pregnancy have an increased incidence of abortion; the risk of malformation in offspring surviving first trimester exposure is not accurately known. In a series of 28 women receiving mercaptopurine after the first trimester of pregnancy, three mothers died undelivered, one delivered a stillborn child, and one aborted; there were no cases of macroscopically abnormal fetuses. Since such experience cannot exclude the possibility of fetal damage, mercaptopurine should be used during pregnancy only if the benefit clearly justifies the possible risk to the fetus, and particular caution should be given to the use of mercaptopurine in the first trimester of pregnancy.

There are no adequate and well controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Source:
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=15904472-4c32-4224-95d3-eb131a7ff9c8#nlm34070-3
Posted 4/15/2014 8:17 AM (GMT -5)
I've been on 6mp for over a year and I haven't had a single infection or cold from it. I'm a guy and I always get scratched up, bruised, and cut and I haven't seen anything from it; no infections, etc. I know one is more prone to getting UTIs, and other common infections. The key thing is being more alert, cautious, and to seek treatment when early signs emerge of an infection. This is important as your immune system is suppressed and therefore less capable of fighting the infection on its own.

Slide 7: What Are the Side Effects of 6MP/AZA?
Serious infections are certainly something we worry about, and the reason is that these medications suppress your immune system. So you might be at risk for having more infections, even more typical infections. I’ll often times tell patients that you might have three colds a year instead of one or two colds a year, and it might last seven days instead of three or four days. But there are also these risks of very serious infections that you wouldn’t get typically because we are suppressing your immune system. These are very rare. And although serious infections might occur 5 percent of the time, life-threatening infections – something we call sepsis – occur very, very rarely. And if you see on that slide, the denominator goes from 100 to 10,000 because out of the 10,000 patients who take these medications, approximately 15 might actually have life-threatening infections."

Source:

Balancing the Risks and Benefits of Treatment For Inflammatory Bowel Diseases by the Crohn's and Colitis Foundation of America

http://www.ccfa.org/assets/pdfs/risk-and-benefits-transcript.pdf
Posted 4/15/2014 8:29 AM (GMT -5)
1. I would get a pneumonia shot now if you haven't had one already, although they only last about 5 years.

2. I'm not an expert on the blood work for these drugs but I think the main thing they are really checking is liver enzymes to make sure it isn't effecting your liver. I don't think they specifically test WBC's, although that does show up on most normal blood tests and would flag a high number.

3. Almost any medicine is a crap shoot but you do have to weigh the risks and weighing the risks doesn't automatically mean that if the risk is low then you go ahead and take the meds. Assuming Ipoop's above figures are correct, I wouldn't want to be one of those 15 out of 10,000 patients with a life threatening infection (I don't believe those figures include the ADDITIONAL small risk of cancers). When you expand those numbers it means that for every ten million people on the drug worldwide for all kinds of conditions (probably a low estimate) there will be 15,000 patients experiencing life threatening infections, again not including the small additional risk of cancers. I wouldn't want to be one of those 15,000 but if UC makes your life miserable, then you might feel those risks are worth it.
Posted 4/15/2014 8:35 AM (GMT -5)
Gary I get both a Complete Blood Count (CBC) and a Liver Function Test (LFT) blood test as part of my regular monitoring of my blood while on 6mp. The CBC checks on white blood cells and lymphocytes. The LFT monitors enzymes, as you said.
Posted 4/15/2014 10:02 AM (GMT -5)
I get the CBC monthly as well, not sure about the LFT though. And my GI did recommend that I get the Pneumovax (pneumonia vaccination) although I have not gotten it.
Like iPoop, I have not gotten sick or had an infection or even a cold since I started 6mp last fall - and I have young children who get colds and viruses all the time.
I also am very healthy for my age, can't discount that - diet and exercise.

So, in short, I have no signs that 6mp has actually compromised my immune system to any degree.
Posted 4/15/2014 10:13 AM (GMT -5)
Gonk, well that's the point exactly as 6mp doesn't shut off your immune system, or cripple it completely. In UC dosages, 6mp just reduces your immune system's capabilities slightly which improves uc symptoms dramatically in some patients. Not sure on the exact percentage that your immune system is reduced, but maybe it's only 85% efficient (based on a guess) or something. When 6mp is used in organ transplants the dosage is way higher, as are the risks accordingly. UC dosages are pretty small comparatively as are the risks.
Posted 4/15/2014 10:13 AM (GMT -5)
I have been on 6mp for 7 months. I had one cold and it was not bad. But other than nothing. Though from last week, I have been sneezing and scratchy throat more like an allergy which I never had it so I was wondering too that is it 6mp realated?

I get my CBC,LFT and CRP often. So far so good. Recently also done blood test to check Thiopourine in my blood at Prometheus lab.

@Gonk are able to get off Uceris? How are you doing without steroid? Blood,urgency etc
Posted 4/15/2014 10:30 AM (GMT -5)
We take this medication at doses way less than cancer patients so our risk for infections is not that same! I took it for 2.5 years and was healthy as a horse, except for my out of control UC symptoms.

Sue
Posted 4/15/2014 11:21 AM (GMT -5)
6MP is not safe for pregnancy.
Posted 4/15/2014 11:37 AM (GMT -5)
Also, since you have your 23and me you can make sure 6mp wont be "bad" for you.
Go to 23andme and Browse your Raw data.
Search for the TPMT gene
It will return many snps. Cross reference here:

www.snpedia.com/index.php/TPMT

A bit more
www.annalsgastro.gr/index.php/annalsgastro/article/view/620/465
www.pharmgkb.org/gene/PA356?tabType=tabVip
www.annalsgastro.gr/index.php/annalsgastro/article/viewFile/362/325

TPMT: *2 (Ala80Pro; rs1800462)
TPMT: *3B (Ala154Thr; rs1800460)
TPMT: *3C (Tyr240Cys; rs1142345)
TPMT: *4 (rs1800584)

Post Edited (PathogenKiller) : 4/15/2014 8:45:37 PM (GMT-6)

Posted 4/15/2014 1:46 PM (GMT -5)
Sorry about that PamSmith, my profile info was a bit outdated.
I am currently on Lialda and 6mp only. I was on prednisone when I started the 6mp. Once I had tapered off the prednisone, I still needed something to hold me until the 6mp was fully in my system, so for that I took Uceris and was on it for 10 weeks. I had no issues, no problems when I stopped the Uceris and was steroid free.
Not to confuse things, but I think good information, from around the time I was off the steroids, I had to stop taking Lialda for a couple of months (long story, but suffice it too say it was a false alarm), so I was only on 6mp. The 6mp alone had me in a pretty good place UC-wise, but I wasn't really 100% flare free, still seeing blood and mucous and stools were not normal. Within two days of starting back on the Lialda, I was 100%, and I have stayed that way since - for about three months now. My GI had told me when we were first considering the 6mp that the two (6mp and mesalamine) work well together, and I can see now that he was absolutely right about that.
Posted 4/15/2014 4:59 PM (GMT -5)
ConquerUC: There is a Facebook chat about IBD and Pregnancy next Wed the 23rd. Info about signing up is on the CCFA website. The doc performing it is to be my daughter's new GI(she is graduating and moving to DC).
Curious to see her in action and thought the topic might interest you. Best
Posted 4/15/2014 5:56 PM (GMT -5)
1) When I was on 6mp I did not get any more infections than I think the average person would... about one per year and it was something like a sinus infection or a sore throat. None of my infections turned into something severe. The hardest thing for me to deal with was the side effects. It completely sapped all of my energy and I literally could not function. I would lay around all day because I just didn't have the energy to do anything.

2) I got pregnant with my 2nd child while taking 6mp. My GI at the time was part of a large research team in Miami and he insisted that the latest research (in 2006) showed that women who took 6mp while pregnant showed NO GREATER INCIDENCE of fetal abnormalities/ miscarriages, etc than women who did NOT take 6mp while pregnant. In other words, the percentage rates were the same as those of the general population. The 2nd link I'm putting on here cites that study. I ended up stopping the 6mp because I go into remission when pregnant and I didn't want to take more meds than necessary, but the "category D" scary stuff has been disproven. I'm sorry I don't have any better links for you. If I find some I wil post them.


Read this post from 2003
http://www.jwatch.org/jg200303250000001/2003/03/25/6-mp-safe-before-and-during-pregnancy

And this one:
http://books.google.com/books?id=KWfRrdmfMv4C&pg=PA58&lpg=PA58&dq=6mp+pregnancy+category&source=bl&ots=nTpZWQ0uST&sig=7oBElizxvJzadfQoq_cQClaNW0U&hl=en&sa=X&ei=NbdNU6neFrHeyQGyjYD4BQ&ved=0CCkQ6AEwAjgK#v=onepage&q=6mp%20pregnancy%20category&f=false
Posted 4/15/2014 9:40 PM (GMT -5)
I think it may be pertinent to talk about why 6MP may work for someone and not for someone else from an epigentics standpoint..



From Wiki:
6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism by inhibiting an enzyme called Phosphoribosyl pyrophosphate amidotransferase (PRPP Amidotransferase). PRPP Amidotransferase is the rate limiting enzyme of purine synthesis.[8] This alters the synthesis and function of RNA and DNA. Mercaptopurine interferes with nucleotide interconversion and glycoprotein synthesis.

---------------------------
So, what is a Purine?
en.wikipedia.org/wiki/Purine

What do Purines do? They make the nucleobases, Adenine and guanine, specifically.
"

Adenine and quanine are very very important as they are 50% of the bases of DNA/RNA. When we rob our microbiome of them, we also rob ourselves... but I digress...

So, if you have a snp on the TPMT gene that is expressing a down regulation of TPMT, Thiopurine compounds like 6-mp can build up to toxic levels causing myelosuppression (infections, immune system weakness)

On the flip side of the coin, If you have an upregulation of snps you can metabolize 6-mp too quickly, using up all your Sam-e and generating alot of homocysteine. And you might find 6mp doesnt really do anything for you.


What you want is the sweetspot between building up to toxic levels and going down a drain.

acco.org/Information/tpmt.aspx


People who react poorly to 6-mp should know you can detox with sam-e. Unfortunately other methylation cycle snps could make sam-e hard for you to tolerate.
www.ncbi.nlm.nih.gov/pubmed/19428339

hstalks.com/main/view_talk.php?t=1121 This is fantastic, wish I could find all of it!





Just for fun




On the other side we have drugs like Fluorauracil that is being used in colon cancer because it inhibits the other branch of SHMT that produces TYMS or thymidylate synthase.


en.wikipedia.org/wiki/Fluorouracil

www.ncbi.nlm.nih.gov/pubmed/11913730

So, Thymidylate Synthase is essential for many forms of life..
en.wikipedia.org/wiki/Thymidylate_synthase
"This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer.The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death."

What is thymineless death, you may ask? :)

" This phenomenon underlies the mechanism of action of several antibacterial, antimalarial and anticancer agents, such as Trimethoprim, Sulfamethoxazole, Methotrexate and Fluorouracil."

Post Edited (PathogenKiller) : 4/15/2014 9:16:24 PM (GMT-6)

Posted 4/17/2014 5:02 PM (GMT -5)
Thank you everyone for the helpful replies,
PK i will check my 23andme but from memory it said that i did not have any snps associated with TPMT downregulation. Also had the thiopuine blood test and my levels were around 10ish (range was 7.5-12.9).

What worries me the most is the category D duing pregnancy, because i want more kids some day and this is not a risk that i like.


Other than that: what about my age, i mean if i go on it now then wouldn't my lifetime risk of complications from it be higher because im on it longer? Or not necessarily?

At the moment, accordingto my recent calprotectin test, i have high level of inflammation even when im in 'symptomatic' remission. So i guess i have to do something, go on something because it means the last 3 years ive been inflamed all the time (inc flares obviously).
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