Azathioprine
A purine antimetabolite that the body turns into mercaptopurine, used to prevent transplant rejection and treat autoimmune diseases.
Also called AZA (abbreviation).
Drug card
- Class
- Antiproliferative immunosuppressant, and an antimetabolite
- How it works
- Releasing mercaptopurine, which blocks purine synthesis in dividing lymphocytes
- Used for
- Preventing kidney transplant rejection
- Rheumatoid arthritis
- Crohn's disease and ulcerative colitis
- Lupus
- Known for
- Bone marrow suppression (low white cells and platelets)
- Liver damage, including veno-occlusive disease
- Pancreatitis
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does azathioprine work?
Azathioprine is a prodrug converted to 6-mercaptopurine, which HGPRT activates to thioguanine nucleotides; these block de novo purine synthesis and are built into DNA, so dividing lymphocytes stop multiplying. TPMT and xanthine oxidase inactivate mercaptopurine, which is why low TPMT activity or allopurinol makes it far more toxic.
Like other antiproliferative immunosuppressants: Lymphocytes activated by an antigen must copy their DNA to multiply, and these drugs cut their supply of purine nucleotides. Azathioprine releases mercaptopurine, whose thioguanine nucleotides block purine synthesis and enter DNA; mycophenolate's active form inhibits IMPDH, the enzyme lymphocytes rely on to make guanine nucleotides. Fewer T and B cells expand, and antibody production falls.
Uses
What is azathioprine used for?
- Preventing kidney transplant rejection
- Rheumatoid arthritis
- Crohn's disease and ulcerative colitis
- Lupus
- Myasthenia gravis
Side effects
Side effects of azathioprine
- Bone marrow suppression (low white cells and platelets)Known forSerious
- Liver damage, including veno-occlusive diseaseKnown forSerious
- PancreatitisKnown forSerious
- Serious and opportunistic infectionsSerious
- Lymphoma, including hepatosplenic T-cell lymphomaSerious
- Skin cancerSerious
- Skin more sensitive to sunlight
- Nausea and vomiting
- Anemia, including macrocytic anemia
- JC virus brain infection (PML)Serious
- Severe skin reaction (Stevens-Johnson syndrome)Serious
- Harm to the fetusSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Inherited low TPMT or NUDT15 activity (found by genetic or enzyme tests) causes severe, even fatal, marrow suppression: a lower dose or another drug is used.
- Allopurinol and febuxostat block xanthine oxidase and raise its toxicity: the dose is cut sharply with allopurinol, and febuxostat is avoided.
- Blood counts are checked weekly at first, then less often, along with liver tests.
- Long-term immunosuppression raises the risk of infections, lymphoma and skin cancer; live vaccines are avoided.
Good to know: NUDT15 deficiency is rare in people of European or African ancestry but much more common in East Asians, who are then at higher risk of severe myelosuppression.
Remember it
A way to remember it
BLIPS
- B
- Bone marrow suppression
- L
- Lymphoma
- I
- Infections
- P
- Pregnancy harm: miscarriage and birth defects
- S
- Skin cancer
Written for biofideX
Its class
Antiproliferative immunosuppressants
Other antiproliferative immunosuppressants with a card:
Easily mixed up with calcineurin inhibitors and antimetabolites.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Azathioprine tablets: label (DailyMed)
- Azathioprine (NCI Thesaurus)
- Azathioprine (NHS)
- Azathioprine 50 mg film-coated tablets: SmPC (emc)
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Targeted therapy and the immune system
Azathioprine is one of 13 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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