What:
This family of medicine is called the thiopurines. They are frequently used to treat patients with Crohn’s disease or ulcerative colitis. They have been around for many years (discovered in the 1950s).
Why:
The aim of this is to prevent flare-ups of your IBD. We want to keep the disease as steady and well controlled as possible, with the least amount of fluctuations requiring steroid (Prednisone) as possible.
When:
We will discuss the best time to start this for your condition, but if you’ve had 2 or more flare-ups in 12 months or other treatments are not working, this is something we should consider together.
How do they work:
They are an immunosuppressive (i.e., dampen down an overactive immune system). They do this by stopping proteins being made in white blood cells (lymphocytes) and preventing development of other white cells.
What are the chances this works for me?
Everyone responds differently and this depends on many different factors. As a broad rule, 2/3 people’s IBD may respond well to this medicine. We often use it in combination with other types of medicine to improve this success rate in treating you.
How much do I take:
I may start with a lower dose, and gradually build to the full level. The dose depends on your weight. For example, a full Azathioprine dose may be around 2mg per 1 kg of your weight, and or 6-MP: 1-1.5 mg/kg.
Before starting, we measure on a blood test a level of enzyme production in your body, called TPMT. This is the enzyme that metabolises these drugs. If the enzyme level is low, you will need less drug to get the same effect, and vice versa for high levels.
I generally check levels of effective drug (6-TGN) and drug by-product (6-MMP) via a blood test initially 3-6 monthly, then space this out to yearly once stable. We now have a very good understanding of the levels of drug required in the body to get good effect, whilst trying to minimize any side effects.
What are the side-effects/risks:
There is about a 10% rate of some adverse effect, usually occurring in the first month. Of these, 10-20% are bad enough to stop the treatment.
Some side-effects may include:
- Nausea (even up to 20% with Azathioprine). We can change to other medicine, 6-MP or TG. Try taking the medicine after food or at bedtime.
- General aches and pains.
- Bone marrow suppression: this is dose related, and why we monitor the blood count very carefully. Due to the mechanism of action (see “how do they work” above), lower levels of white blood cells can occur in up to 27%.
- Infections: As this medicine dampens down the immune system, you may be more susceptible to some infections.
- Allergy/Pancreatitis (inflammation of the pancreas causing severe abdominal pain) – we have no idea to whom or why this might occur but thankfully is rare.
- Hepatitis (inflammation of the liver – often painless): we monitor the liver with blood tests. Stopping the medicine if this occurs frequently resets things back to normal.
- Lymphoma: The risk of lymphoma in the general population is 2 in 10,000. The risk of lymphoma if you have IBD and take a thiopurine is 4 in 10,000. This is where you may have heard “taking Azathioprine doubles your risk of developing cancer.” The risk, albeit low increases over time exposed, and decreases when you stop it.
- Non-melanoma skin cancer: You must be extra sun-smart, particularly in New Zealand with a hat and sunscreen. This risk is thought to persist over your lifespan, even if you stop the medicine.
What monitoring is required:
Prior to starting the medicine, I check your blood count, kidney function, liver function, and for latent (dormant) infections and immunisation status. Infections which are currently suppressed may reactivate if you are given immune-suppression, so this is important to know.
I usually request a blood test to check blood levels and liver tests weekly for 1 month, monthly for 2 months, then 3 monthly once stable.
When will it start to work?
It takes some time for these medicines to build up in the body, and people only usually notice an effect after 3 months, with some patients taking up to 6 months. This is why often other medicine is given at the same time.
When can I stop it?
The goal of the medicine is to stop flares. If you have had no symptoms for 3-4 years, there is no inflammation on stool tests or colonoscopy, we can have a good discussion about the pros, cons, risks and alternatives of stopping.
FAQs:
Q: Does it interact with my other medicines:
A: Medicines to treat gout (in particular Allopurinol and Febuxostat) react strongly with this class of drugs and must not be used together without close monitoring.
Q: What other conditions does this treat?
A: It is used after some organ transplants to keep the body from rejecting the organ (at much higher doses). It is also used to treat rheumatoid arthritis. It is also used for some autoimmune skin conditions. It is not used as chemotherapy.
Q: Is there any effect on fertility?
A: It is thought to be safe for men, with limited studies suggesting no effect on sperm. For woman, there is more risk to the baby if you stop treatment and become unwell. No studies have shown any increased risk of miscarriage or birth defects in babies to parents taking these medicines. There is a small amount of medicine in breast-milk up to four hours following taking it, but it is considered safe to breastfeed.
Q: Should I take it with food:
A: As long as it is the same time of day, it doesn’t matter too much. Don’t have 6-MP with milk.
Q: Can I get vaccinations whilst I am on this?
A: Yes, you should get the annual flu vaccination. You must, however, not have any live vaccines. This includes: VZV (i.e. chicken pox), measles, mumps, rubella, vaccinia, rotavirus, yellow fever, Sabin polio vaccine (the Salk inactivated vaccine is safe), BCG (TB).
More information:
Formal New Zealand Patient Medsafe datasheet
https://www.medsafe.govt.nz/Profs/Datasheet/i/Imurantab.pdf
New Zealand Formulary: