Usual Adult Dose for Renal Transplant

Initial dose: 3 to 5 mg/kg orally or IV once a day, beginning at the time of transplant
Maintenance dose: 1 to 3 mg/kg orally or IV once a day

Comments:

• In a minority of cases, therapy has been started 1 to 3 days before transplantation
• The dose should not be increased to toxic levels because of threatened rejection

Usual Adult Dose for Rheumatoid Arthritis

Initial dose: 1 mg/kg (50 to 100 mg) orally or IV per day given in 1 to 2 divided doses
Maintenance dose: Lowest effective dose
Maximum dose: 2.5 mg/kg orally or IV per day
Duration: At least 12 weeks

Comments:

• Dose may be increased by 0.5 mg/kg/day (or approximately 25 mg/day), after 6 to 8 weeks of starting treatment and thereafter at 4 week intervals if necessary.
• Gradual dose reduction is recommended to reduce the risk of toxicities.
• Therapeutic response occurs after several weeks of therapy, usually 6 to 8 weeks. Patients not improved after 12 weeks can be considered refractory.
• Azathioprine may be continued long-term in patients with clinical response.

Usual Adult Dose for Crohn's Disease - Acute

Studies:
1.5 to 4 mg/kg per day for 10 days up to 52 weeks

Usual Adult Dose for Crohn's Disease - Maintenance

Studies:
1.5 to 4 mg/kg per day for 10 days up to 52 weeks

Usual Adult Dose for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Study (n=14)
2 to 3 mg/kg orally once a day for 9 months

Usual Adult Dose for Atopic Dermatitis

Study (n=37)
2.5 mg/kg orally once a day, in the morning, for 3 months

Usual Adult Dose for Sarcoidosis

Study (n=11)
Initial dose: 2 mg/kg per day in combination with prednisolone 0.6 to 0.8 mg/kg per day, with prednisolone reduced to 0.1 mg/kg within 2 to 3 months
Maintenance dose: 2 mg/kg per day with prednisolone 0.1 mg/kg per day for 21 to 22 months

Usual Adult Dose for Ulcerative Colitis

Study (n=9)
IV: 20 to 40 mg/kg via IV infusion over 36 hours or 40 mg/kg as three 8-hour infusions over 3 days followed by oral azathioprine
Oral: 2 mg/kg orally per day beginning the day after completion of the IV loading dose

Study (n=12)
50 mg per day for 2 weeks, then 2 to 2.5 mg/kg per day plus mesalamine 500 mg orally 3 times a day; these drugs were started immediately after signs of remission was achieved (mean: 14.5 days) with cyclosporine IV (4 mg/kg/day)

Usual Adult Dose for Uveitis

Study (n=14)
Treatment of choroidal neovascularization: 1 to 1.5 mg/kg orally per day, in combination with prednisolone and cyclosporine

Usual Adult Dose for Multiple Sclerosis

Study (n=6)
Patients refractory to interferon beta-1b:
Initial dose: Azathioprine should be titrated up to 1.5 mg/kg per day over 1 month, followed by 50 mg increments in 6-month intervals, concomitantly with 8 million international units subcutaneous interferon beta-1b on alternate days
Maintenance dose: 2 mg/kg per day

Usual Adult Dose for Systemic Lupus Erythematosus

Studies:
1 to 3 mg/kg actual body weight (ABW)/day orally or IV once a day

Study (n=55)
Diffuse proliferative lupus glomerulonephritis: Sequential therapy starting with prednisone (1 mg/kg/day) for 8 to 10 weeks, gradually tapering to maintenance dosage of 5 to 10 mg/day, together with oral cyclophosphamide (1 to 2 mg/kg/day) for 6 to 9 months followed by azathioprine 50 to 100 mg/day

Usual Adult Dose for Chronic Active Hepatitis

Study (n=72)
Autoimmune hepatitis: 1 to 2 mg/kg per day, concomitantly with prednisolone (5 to 15 mg/day) for a minimum of 1 year (average 5 years)

Usual Adult Dose for Takayasu's Arteritis

Study (n=15)
2 mg/kg ABW/day for 1 year in combination with prednisolone taper

Usual Pediatric Dose for Atopic Dermatitis

Study (n=37)
Greater than 17 years: 2.5 mg/kg orally once a day, in the morning, for 3 months

Usual Pediatric Dose for Organ Transplant - Rejection Prophylaxis

Initial dose: 3 to 5 mg/kg orally or IV once a day, beginning at the time of transplant
Maintenance dose: 1 to 3 mg/kg orally or IV once a day

Usual Pediatric Dose for Eczema

Study (n=91)
Greater than 6 years: 2.5 to 3.5 mg/kg per day in patients with normal levels of thiopurine methyltransferase

Usual Pediatric Dose for Systemic Lupus Erythematosus

Case Study (n=67)
Lupus Nephritis:
Greater than 5 years: 2 to 3 mg/kg per day (maximum dose: 150 mg/day)
Dose should be titrated to maintain a total white blood cell count between 3 and 4 x 10(3) cells/mL.

Renal Dose Adjustments

Lower doses may be required; however, no specific guidelines have been suggested.

Liver Dose Adjustments

Dose adjustments may be required; however, no specific guidelines have been suggested.

Dose Adjustments

Dosage reduction or alternative therapy may be required in patients with reduced thiopurine S-methyltransferase (TPMT) activity.

Concomitant allopurinol: Azathioprine dose should be reduced to 25% to 33% of the usual dose. Further dose reduction or alternative therapies should be considered for patients with low or absent TPMT activity.

Precautions

US BOXED WARNING(S):

• Chronic immunosuppression with azathioprine increases the risk of malignancy.
• Post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) has been reported in patients with inflammatory bowel disease.

• Inform patients of the risk of malignancy with azathioprine.

Dialysis

Data not available; approximately 45% of an azathioprine dose is removed by hemodialysis.

Other Comments

Administration advice:

• IV: Doses should generally be infused over 30 to 60 minutes; it may be administered over 5 minutes and, for the daily dose, over 8 hours

• IV: Once reconstituted, the solution for injection should be used within 24 hours

• TPMT testing may be required in patients with abnormal CBC results that do not respond to dose reduction
• Treatment cessation may be required for severe hematologic or other toxicity
• Appropriate handling procedures for immunosuppressive agents according to local guidelines should be considered

• Hematologic: CBC, including platelet count, weekly for the first month, twice a month for the second and third months, then once a month or more often if necessary
• Hepatic: Liver function
• Immunologic: Signs and symptoms of infection

• Minimize exposure to sunlight and UV light by wearing protective clothing and using a sunscreen with a high protection factor
• Report any unusual bleeding or bruising, or signs and symptoms of infection