Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is caused by inflammation of the GI tract due to an overactive immune system, and drugs that suppress the immune system are used to help control the disease. Azathioprine and 6 mercaptopurine are two immunosuppressive drugs. Azathioprine is metabolized into 6 mercaptopurine, and both drugs act by reducing white blood cells in the body. Although 6mercaptopurine and azathioprine suppress the immune system, they are not hormones and do not have the same side effects as hormones.
Why should I use azathioprine?
If you start using one of these drugs, it usually means that your disease is more difficult to control, with severe or moderately active disease. Or you are dependent on hormones and cannot stop taking them, or hormone therapy is not working for you. Or you are using a combination of drugs to improve the efficacy of your treatment during classical gram therapy. Azathioprine and 6 mercaptopurine take about 3 months to start working, so your current dosing needs to be maintained as is or increased until the immunosuppressants start working.
Are there any conditions in which I should not use azathioprine?
1. Hypersensitivity to azathioprine or 6 mercaptopurine.
2. Severe infections, including viral hepatitis.
3. Tuberculosis, both active and inactive.
4, Severely impaired liver function or severe bone marrow hematopoietic dysfunction, severe renal disease.
5.Untreated malignant disease.
6.Previous history of pancreatitis, or current pancreatitis.
7.Has received live vaccines (such as BCG, yellow fever vaccine, chicken pox vaccine, etc.) within the past four weeks.
8. Pregnancy, which should only be considered if the benefits from the use of the drug outweigh the risks.
It is still controversial whether immunosuppressive drugs can be taken before or during pregnancy. The final decision to use or not to use, is a personal decision, but need to know the risks and benefits of using the drug. Overall, these types of immunosuppressive drugs are relatively safe to take during pregnancy and the risk of birth defects is very low. For a woman who is taking immunosuppressants during pregnancy but has well-controlled disease, the chances of miscarriage in early pregnancy are the same as for a woman who is not taking immunosuppressants during pregnancy but has active IBD disease, and we prefer that the expectant mother maintain a healthy status prior to pregnancy. Please consult your doctor for details.
9. During breastfeeding.
Azathioprine can be secreted into breast milk, but its concentration in breast milk drops sharply 4 hours after taking the drug. Therefore, some experts believe that it is feasible to take the drug for 4 hours before breastfeeding. It is best for you to consult your obstetrician and gynecologist whether to take azathioprine while breastfeeding, and the final decision to use or not is a personal one.
What are the possible adverse effects of taking azathioprine?
1. Bone marrow suppression (leukopenia, granulocyte deficiency, thrombocytopenia, and complete blood cytopenia).
The most common side effect is a decrease in white blood cells. It may be possible to solve this problem with only a slight adjustment of your dose of medication. This is the reason why it is important to have blood tests as prescribed by your doctor.
Since these medications can lower your white blood cells, we need to monitor closely for changes in your white blood cell count. These medications can also lower your red blood cells (which can mean anemia) and platelet counts. So once you start treatment, a complete blood count (CBC) needs to be tested 1 week after starting the medication or after each medication dose adjustment.
Your white blood cells may be so low that you are at risk of infection or even life-threatening. Severe leukopenia (<1000/mm3) or granulocyte deficiency (<500/mm3) may occur as: feeling unwell; usually with high fever or chills; inflammation of the tonsils; stomatitis; swollen lymph nodes; headache; nausea; cough; vulvodynia and anal inflammation.
2. Pancreatitis.
The most serious side effect, but one that rarely occurs, is pancreatitis. It occurs in about 5% of patients. It usually occurs shortly after starting the drug. Symptoms of pancreatitis are nausea, vomiting, and upper abdominal and/or back pain. There may also be no symptoms and only elevated lipase/amylase found on blood monitoring. If you develop any of these conditions, tell your doctor as soon as possible. Usually pancreatitis clears up after you stop taking the medication, but once you have pancreatitis, it may mean that you are not able to use these medications again.
3.Allergic reaction
4. Liver damage.
Hepatotoxicity; cholestatic jaundice; nodular regenerative hyperplasia; purpura.
Azathioprine and 6 mercaptopurine are metabolized through the liver, so blood tests to monitor liver function are also very important and can be done at the same time as other blood tests.
Sometimes your liver is not carrying a heavy load and you may not even notice it until you have blood work done. Rarely, your skin or the whites of your eyes may turn yellow (jaundice). This can usually be improved by adjusting the dose of medication. However, liver function needs to be monitored closely until it returns to normal.
5. Muscle and joint pain.
6. Nausea, vomiting, and upper abdominal pain.
Sometimes, you may have some nausea or poor appetite while taking the drug. It may take a period of adjustment and get better soon. If nausea occurs, then taking the medicine at night before going to bed may help.
7. Tumor risk.
6 Mercaptopurine and azathioprine in high doses during anti-rejection and chemotherapy have been found to cause tumors, but because the doses used in IBD are very small, the risk of tumors is also very low.
8. Other
Guidance on blood monitoring of azathioprine.
Adverse reactions to azathioprine often occur during the first 1-3 months of taking the drug, so close monitoring is needed for the first 3 months. You will need to have weekly blood tests for the first 8 weeks and will need to be concerned about your tolerance to azathioprine and possible adverse reactions. The monitoring interval can be gradually extended as treatment progresses.
However, bone marrow suppression can occur after you have been taking azathioprine for several years and may be triggered by certain factors, such as a viral infection of the bone marrow or an interaction with other drugs you have just started taking. Myelosuppression can occur even if thiopurine methyltransferase (TPMT) levels are normal. Therefore, you will need to have blood tests at least every 3 months during the course of long-term drug use. If there are symptoms or suspected symptoms of an adverse reaction, especially myelosuppression, a shorter monitoring interval is required.
It is important to emphasize: regular monitoring is required throughout the course of azathioprine treatment!
Some adverse reactions (pancreatitis, pneumonia, myalgia, arthralgia) occur independently of the dose of azathioprine and are due to immune-mediated hypersensitivity reactions. If these adverse reactions occur, the drug must be discontinued. Some patients may be able to tolerate 6-mercaptopurine, but it should be taken with caution and monitored frequently.
Other adverse reactions are dose related and dose adjustment is required for these adverse reactions (myelosuppression, gastrointestinal reactions).