Dosing and uses of Azasan, Imuran (azathioprine)
Adult dosage forms and strengths
tablet
- 50mg
- 75mg
- 100mg
powder for injection
- 100mg/vial
Kidney Transplantation
Prevention of transplant rejection
3-5 mg/kg/day IV/PO initially on day of transplant or 3 days before transplant (rare)
Maintenance: 1-3 mg/kg/day IV/PO
Rheumatoid Arthritis
1 mg/kg/day IV/PO initially in single daily dose or divided q12hr; may be increased by 0.5 mg/kg/day after 6-8 weeks, then by 0.5 mg/kg/day every 4 weeks; not to exceed 2.5 mg/kg/day
Maintenance: Reduce daily dose by 0.5 mg/kg every 4 weeks until lowest effective dosage is reached
Lupus Nephritis (Off-label)
Induction and maintenance therapy for lupus nephritis (2012 American College of Rheumatology guidelines)
2 mg/kg/day PO with or without low-dose corticosteroids
Crohn Disease (Off-label)
Maintenance, remission, or reduction of steroid
2-3 mg/kg PO once daily
Ulcerative Colitis (Off-label)
Maintenance, remission, or reduction of steroid
1.5-2.5 mg/kg PO once daily
Chronic Refractory Thrombocytopenic Purpura (Off-label)
1-2 mg/kg PO once daily to maximum daily dose of 150 mg for at least 3-6 months before typical response is observed
Dosing considerations
- Lower dosage (100 mg/day) is reported effective in some patients
- Longer treatment duration (up to 84 months) is reported in some patients
Pediatric dosage forms and strengths
tablet
- 50mg
- 75mg
- 100mg
powder for injection
- 100mg/vial
Juvenile Idiopathic Arthritis
1 mg/kg/day IV/PO initially in single daily dose or divided q12hr; may be increased by 0.5 mg/kg/day after 6-8 weeks, then by 0.5 mg/kg/day every 4 weeks; not to exceed 2.5 mg/kg/day
Maintenance: Reduce daily dose by 0.5 mg/kg every 4 weeks until lowest effective dosage is reached
Transplantation (Off-label)
Prevention of transplant rejection
3-5 mg/kg/day IV/PO initially on day of transplant or 3 days before transplant (rare)
Maintenance: 1-3 mg/kg/day IV/PO
Lupus Nephritis (Off-label)
Induction and maintenance therapy for lupus nephritis (2012 American College of Rheumatology guidelines)
<12 years: Safety and efficacy not established
>12 years: 2 mg/kg/day PO with or without low-dose corticosteroids
Azasan, Imuran (azathioprine) adverse (side) effects
>10%
Leukopenia (28-50%)
Infection (20%)
<1%
Lymphoma
Frequency not defined
Abdominal pain
Alopecia
Arthralgia
Bacterial, fungal, protozoal, viral infections
Bone marrow suppression
Diarrhea
Fever
Hepatotoxicity
Macrocytic anemia
Myalgia
Nausea or vomiting
Rash
Skin cancer
Steatorrhea
Sweet syndrome (acute febrile neutrophilic dermatosis)
Thrombocytopenia
Warnings
Black box warnings
Chronic immunosuppression with this purine antimetabolite increases neoplasia risk, mutagenic risk, and hematologic toxicities
Reported malignancies include posttransplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease
Prescribing physicians should be familiar with mutagenic potential and with possible hematologic toxicities
Contraindications
Documented hypersensitivity
Pregnancy, lactation
Rheumatoid arthritis: Patients previously treated with alkylating agents
Cautions
Long-term use increases risk of neoplasia
Increased risk of infection and hepatotoxicity
Cases of JC virus-associated infection resulting in progressive multifocal leukoencephalopathy (PML), sometimes fatal, reported in patients treated with immunosuppressants, including azathioprine
Hepatosplenic T-cell lymphoma
- Rare postmarketing cases of HSTCL reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with tumor necrosis factor (TNF) blockers
- Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
- HSTCL is an aggressive, rare type of T-cell lymphoma that is usually fatal
- Most reported cases with TNF blockers have occurred in context of concomitant treatment with azathioprine or 6-mercaptopurine (6-MP), though cases have been reported with azathioprine or 6-MP alone
- In the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network, HSTCL cases have been identified in association with the following drugs: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), 6-MP (3)
Pregnancy and lactation
Pregnancy category: d
Lactation: Drug excreted at low levels in breast milk; use not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Azasan, Imuran (azathioprine)
Mechanism of action
Purine antimetabolite, converted to 6-MP; may inhibit synthesis of DNA, RNA, and proteins; interferes with cellular metabolism; may inhibit mitosis
Absorption
Well absorbed orally
Duration: Variable (crosses placenta)
Peak plasma time: PO, 1-2 hr
Peak plasma concentration: <1 mcg/mL
Distribution
Protein bound: 30%
Metabolism
Metabolized in liver
Metabolites: 6-MP, 6-thiouric acid
Elimination
Half-life: Parent drug, 12 min; 6-MP, 0.7-3 hr; slightly prolonged in end-stage renal disease
Dialyzable: Partially
Excretion: Urine (primarily as metabolites)
Administration
Oral suspension of 50 mg/mL requires extemporaneous compounding by pharmacist
IV Incompatibilities
Stable in neutral or acid solutions; in alkaline solutions, hydrolyzed to 6-Mp
IV Administration
Can be administered by IV push over 5 minutes at concentration not exceeding 10 mg/mL
Can be further diluted with NS or D5W and administered by intermittent infusion over 30-60 minutes (usual approach); however, infusions over periods ranging from 5 minutes to 8 hours have been done
Storage
Store powder at room temperature (25°C); reconstituted solution is stable for 2 weeks at room temperature but may be less stable under refrigeration
Protect from light
Because there are no preservatives, drug must be used within 24 hours
