IBD Basics: Azathioprine & Mercaptopurine – 6-MPs

IBD Basics: Azathioprine & Mercaptopurine – 6-MPs

What are 6-MPs? & Why are they important?

Azathioprine and Mercaptopurine are members of the thiopurine family of medication, and they are used to treat both UC and Crohn’s disease; the most common types of IBD. Whilst they get used for both types of IBD, 6-MP’s are more widely used in UC, but only by a small margin. 1 in 5 patients who take Azathiopurine achieve remission and can be a good step stone to reducing or coming of steroids in the long term. They have been used since the 1960’s and have a good history of working well in most patients.

Why are they used to treat IBD?

6-MPs are immunosuppressants, which work to reduce the active inflammation in the body; for IBD this would be the gut. Azathioprine reduces the number of white blood cells in the body – the immune system relies on these white blood cells for many reasons – and in turn by reducing them it interrupts the immune system’s function. This action halts a flare up and helps reduce dependency on steroids, and in the long term can help actively prevent flare ups in some patients.

  • Azathioprine is taken as an oral tablet. It is also know as by the brand names of Imuran, Asazan and Azapress.
  • Mercaptopurine is also taken as an oral tablet. This is sometimes know as 6-Mercaptopurine or Puri-ethanol.

There are many factors for taking 6MPs one of which is where you are in the progress of remission. Typically, 6MPs are not offered as a first line treatment option, but more when a patient has reached remission from another medication or they need to come off long term steroids.

Mercaptopurine is used less often than Azathioprine in the UK. Patients who cannot tolerate Azathioprine, due to side effects, may still be able to take Mercaptopurine as an alternative.

How are they used to treat IBD?

The dose of these drugs will depend on your body weight and with the severity of your condition. You may be started on a low dose which is then increased gradually. Those with liver problems or the elderly will typically stay on a lower dose for the safety due to other conditions.

  • Azathioprine: the usual dose is between 1.5 mg and 2.5 mg per kg of body weight per day.
  • Mercaptopurine: the dose is usually half that of Azathioprine, ranging from 0.75 – 1.5 mg per kg of body weight per day.

Doses are also based on the levels of enzymes in your body that break down the drugs.

In general, Azathioprine tablets need to be taken with food and swallowed with a glass of water; while Azathioprine film coated tablets and Mercaptopurine tablets need to be taken with a glass of water one hour before or three hours after food.

These drugs take a long while to work in the system, which is one reason why they are not given as a first response to an acute IBD flare up. They can take 3-6 months before the full effectiveness of the drug and the dosage is felt. It is important whilst taking these medications to take them on time and not to skip doses. Many patients stay on these medications for years as they primarily protect the body from big flare ups, due to its immunosuppressant nature.

Side Effects & Important Information

  1.  As these medications are immunosuppressants, it is important to note that they reduce the entire immune system, which means you are more likely to catch colds, the flu and viruses whilst taking these medications.
  2. Women on these medications have an increased risk of contracting HPV – the virus that causes cervical cancer – so it is important to keep on top of your regular cervial screening (smear test).
  3. Prior to starting; there is a number of tests required: 1) your levels of the enzyme thiopurine methyl transferase (TPMT) will be measured from your blood. This test can help to predict who is more likely to experience side effects with Azathioprine or Mercaptopurine. 2) You will be screened for immunity to the chickenpox virus and infections such as Hepatitis B and C as well as human immunodefienciy virus. Screening for TB can also be required depending on your exposure and immunisations.
  4. Whilst on this treatment, you will have your blood monitored for any rise in the TPMT as well as your LFTs too. This is to keep an eye on function of your liver as these medications  suppress normal bone marrow function and occasionally cause liver complications. Regular tests are vital as abnormalities in the blood may not produce symptoms straightaway.
  5. Usually these blood tests are weekly to begin with, then fortnightly once your dose has stablised. Keeping up with these blood tests are important to help your IBD team determine if and when these medications become to be more risky than beneficial.
  6. Kidney function should be monitored every six months.
  7. These blood tests can take place in a hospital setting or if your IBD team allows, your GP practice can do this too; as long as the information is share between the two.
  8. Azathioprine and Mercaptopurine increase the skins sensitivity to sunlight so its important to wear sunscreen when outside in the sunshine.
  9. It’s important to not take Mercaptopurine with milk as this has been shown to inhibit the effectiveness of the drug in the system.
  10. If you are pregnant or wanting to get pregnant in the near future, it is best to not start this medication as it is not safe during pregnancy for women or for men who want to conceive. However, some clinicians can discuss the benefits and risks with you on an individual basis.
  11. Azathioprine is often used as a long-term maintenance drug. It is not known to reduce in effectiveness over time, so some patients remain on it indefinitely.

Side effects from these medications can be:

  • Nausea and vomiting; usually common in the first couple weeks of treatment. It might be worth taking the medication after food, or in two smaller doses in the day to help reduce this side effect.
  • Loss of appetite.
  • Allergic reaction to the drug which may include dizziness, nausea, vomiting, diarrhoea, fever, shivering, skin rash or pain in muscles or joints.
  • Suppression of normal bone marrow function, which can cause reductions of red blood cells (anaemia), white blood cells (leucopenia) and platelets (thrombocytopenia). Regular monitoring should pick up a reduced blood count. Symptoms can be breathlessness and bruising easily.
  • Inflammation of the pancreas (pancreatitis)
  • Yellowing of the skin and eyes (jaundice)
  • Problems with liver; which can cause acute pain in the abdomen. Regular blood testing should pick up any liver issues.
  • Diarrhoea; which may be difficult to distinguish from symptoms of a flare-up.
  • Lung inflammation (pneumonitis)
  • Increased risk of certain types of cancer (lymphomas, cancer of cervix/vulva and skin cancer) This is an inherent risk with taking immunosuppressants as the body does not have the full advantage to fight off any possible cancer cells in their early stage. If you are concerned about this risk; it is always a good idea to discuss this in detail with your IBD team prior to starting treatment.

If you develop any of the follow:

  • A sore throat, unexplained bruising, bleeding, or mouth ulcers
  • Nausea, vomiting, abdominal discomfort, jaundice or dark urine
  • Central acute abdominal pain
  • Signs of an allergic reaction including hives (itchy wheals on the skin), difficulty breathing, swelling of the face, lips, tongue or throat.

Please contact your IBD team in the first instance, then your GP. These are serious side effects and would need investigating right away.

Your doctor should talk through the risks and benefits before you start 6-MPs. Let your doctor or IBD nurse know about any new symptoms you develop, whenever they occur.

My Experience
 I had my first taste of Azathioprine a couple of months after I was diagnosed and was back in hospital with a flare up and C Diff. We had just tried me on the low dose in a clinic, a week prior to that particular admission, and I had to be admitted via an ambulance because one morning. On top of the flare up symptoms, I also couldn’t breathe very well or stand up at all. Turns out, my body had a bad reaction to the medication; so we discontinued straight away, got my flare up under control with IV steroids and antibiotics for the C Diff infection; and applied for Humira (adalimumab) at the same time. I remember feeling very much like my body was fighting a disease that was unpredictable, uncontrollable and always gave me the worst side effects of everything I took to try and fight it. This was a feeling I have felt many times since, and probably will continue to feel to some extend but I have always continued to fight against my disease.
I did try Mercaptiopurine a year or two after the period mentioned above. It was the middle ground for helping me push towards remission. Given my previous reaction to Azathioprine, we weren’t too hopefully for this one to work, and low and behold it didn’t. I struggled without a treatment plan for a while as my GI changed over, had some success with steroids helping damped down my symptoms but ultimately, I needed to return to biologics; this time it would be Infliximab.
I am glad we tried those two drugs though. I am always wistful about them because whilst I was struggling through hell, I have always wondered if we gave them enough time. But given the circumstances at the time, we probably did the right thing, discontinuing. It was right before we got me onto Inflixmab did we find out that my Crohn’s was now in my small bowel, I needed a targeted treatment for that, and biologics do that the best.
Even though it wasn’t an appropriate or successful treatment option for me, I did blog about it:

New Week, New Meds: The Life of a Chronie – February 5th, 2013

When you Literally Can’t get out of Bed – February 10th, 2013

Pred, Pred and MORE Pred – April 3rd, 2013

A Bag of Nerves – November 12th, 2013

I ran a Twitter poll for this post, result can be found here.

Have you had to take 6 MPs for your IBD? Have you found them useful as a treatment option? Have you any bad experiences, side effects or reactions? If so, what happens/ed next?

Do you have any questions or queries? Or just want to share your own experiences? Leave me a reply or tweet me @sapphire20 or find my blog page on Facebook!

Sources: 

Crohn’s and Colitis: UK: Azathioprine and Mercaptopurine (pdf)

IBD Relief: Azathioprine for Crohn’s disease and Ulcerative Colitis

Crohns Colitis Foundation: Immunomodulators Fact Sheet (pdf)

NICE: Azathioprine Guidelines

Journal of Crohns and Colitis (JCC): Long-term Efficiacy of Azathioprine in Ulcerative Colitis

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