Drug reference

Azathioprine

Immunosuppressant · Inflammatory Bowel Disease agent

ImmunosuppressantInflammatory Bowel Disease agentATC null

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Teratogenic in animals; do not discontinue in transplant patients; supervise in specialist units

FDA category + note

Top interactionssee all 12 →

FebuxostatContraindicatedDatabaseKimi deep-research + Cla
AllopurinolSevereTextbook-citedKDT 7e · p948
AdalimumabSevereDatabaseDDInter
BaricitinibSevereDatabaseDDInter

Mechanism

Azathioprine is a prodrug converted to 6-mercaptopurine, which is then metabolized by hypoxanthine guanine phosphoribosyl transferase (HGPRT) into active 6-thioguanine nucleotides (6-TGNs). These 6-TGNs are incorporated into DNA and RNA, acting as false purine analogs. This incorporation disrupts nucleic acid synthesis and function, leading to the arrest of DNA replication and cytotoxicity, particularly in rapidly proliferating immune cells. The resulting inhibition of lymphocyte proliferation produces its immunosuppressive effect.

Indications

Induction of remission in Crohn’s disease (as add-on to a corticosteroid or budesonide) in patients with two or more inflammatory exacerbations in a 12-month period, or when the corticosteroid dose cannot be reduced.Maintenance of remission in Crohn’s disease (as monotherapy) when previously used with a corticosteroid to induce remission.Maintenance of remission in Crohn’s disease (as monotherapy) in patients not previously treated with azathioprine but with adverse prognostic factors (e.g., early age of onset, perianal disease, corticosteroid use at presentation, and severe presentations).Maintenance of remission in ileocolonic Crohn’s disease after complete macroscopic resection within the previous 3 months (in combination with up to 3 months’ postoperative metronidazole or alone).Inflammatory bowel diseaseAutoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis)adjunct for prevention of organ transplant rejectionrheumatoid arthritissevere IBDsteroid-resistant or steroid-dependent IBDadjunct to glucocorticoids and biologics in moderate-to-severe Crohn’s disease and ulcerative colitismaintenance of remission in both diseasesprevention or delay of recurrence of Crohn’s disease after surgical resectiontreatment of fistulas in Crohn’s diseasecombination with infliximab for induction of remission and mucosal healing in steroid-resistant patientsorgan transplantationmyasthenia gravis (advanced cases, inhibits NR-antibody synthesis)Autoimmune diseases (rheumatoid arthritis, ulcerative colitis)

Dosing

Adult: Transplant rejection: 1-2.5 mg/kg daily. RA/SLE: initially up to 2.5 mg/kg daily in divided doses, maintenance 1-3 mg/kg daily. Crohn's/UC: 2-2.5 mg/kg daily. Myasthenia gravis: initially 0.5-1 mg/kg daily, increased to 2-2.5 mg/kg daily over 3-4 weeks.
Renal adjustment: Reduce dose in renal impairment
Hepatic adjustment: Reduce dose; monitor hepatic function
Max dose: 3 mg/kg daily (rarely)

Pharmacokinetics

Onset

Slow (takes up to 1 year)

Bioavailability

60 ± 31%

Protein binding

—

Metabolism

Undergoes S-methylation catalyzed by thiopurine methyltransferase (TPMT) for detoxification.

Excretion

Renal clearance has little effect on efficacy or toxicity

Contraindications

Absent TPMT activity (for eczema indication)
Very low TPMT activity (for eczema)
Genetic deficiency in thiopurine methyltransferase (TPMT) (risk of severe toxicities)
allopurinol coadministration

Side effects

Common

Bone marrow depression (dose-related)Increased infection riskLeucopeniaThrombocytopeniaNauseabone marrow suppression (leukopenia > thrombocytopenia > anemia)susceptibility to infectionshepatotoxicityalopeciagi toxicityfeverrasharthralgiasvomiting

Serious

Agranulocytosis
Hepatotoxicity
Pancreatitis
Lymphoma risk (long-term)
Severe cutaneous adverse reactions
pancreatitis (about 5% of patients)
bone marrow suppression (major dose-related effect)
elevations in liver function tests (dose-related)
cholestatic hepatitis (relatively rare)
increased incidence of malignancy (non-Hodgkin lymphoma, 4-fold increase)
severe bone marrow toxicity (with thiopurine methyl transferase (TPMT) deficiency)
Toxicity enhanced in TPMT deficiency (myelosuppression, mucositis, gut damage)

Pregnancy & lactation

Pregnancy

Teratogenic in animals; do not discontinue in transplant patients; supervise in specialist units

Drug interactions

Febuxostat

Contraindicated

Database

Febuxostat inhibits xanthine oxidase, the enzyme that metabolizes azathioprine and 6-MP to inactive metabolites. Co-administration causes massive increases in azathioprine/6-MP levels, leading to severe myelosuppression, pancytopenia, and hepatotoxicity.

Absolute contraindication. Do NOT use febuxostat in patients on azathioprine or 6-MP. If gout treatment needed, use colchicine, NSAIDs, or allopurinol (also contraindicated with azathioprine — need dose reduction of azathioprine by 50-75%).

Source: Kimi deep-research + Cla

Allopurinol

Severe

Textbook-cited

Severe myelosuppression due to 6-MP accumulation.

Reduce azathioprine dose to one-third

Source: KDT 7e · p948

Adalimumab

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter