Azathioprine Dosage

This dosage information may not include all the information needed to use Azathioprine safely and effectively. See additional information for Azathioprine.

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

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; in a few cases, therapy has been started 1 to 3 days before transplantation
Maintenance dose: 1 to 3 mg/kg orally or IV once a day

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
Titration: May increase in increments of 0.5 mg/kg/day (up to a maximum dose of 2.5 mg/kg/day), beginning at 6 to 8 weeks and thereafter at 4 week intervals
Maintenance dose: Gradual dosage reduction should be attempted to reduce risk of toxicity. Maintenance therapy should be at the lowest effective dose. The dose can be lowered by 0.5 mg/kg or approximately 25 mg/day every 4 weeks.

Therapeutic response occurs after several weeks of therapy, usually 6 to 8 weeks, and should be tried for at least 12 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 daily, 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

CrCl 10 to 50 mL/min: The dose should be reduced to 75% of the normal daily dose.
CrCl less than 10 mL/min: The dose should be reduced to 50% of the normal daily dose.

Liver Dose Adjustments

The conversion of azathioprine to 6-mercaptopurine may be impaired in patients with liver disease. Dosage adjustments may be necessary.

Dose Adjustments

Doses should be adjusted to maintain the white blood cell count greater than 4000 to 5000/mm3 in organ transplant patients. The dose should not be increased to toxic levels due to threatened rejection. Discontinuation may be required for severe hematologic or other toxicity, even if rejection of the homograft may occur due to drug withdrawal.

Before starting treatment, measurement of enzyme thiopurine methyltransferase (TPMT) will detect heterozygotes, whose dose will need to be cut in half, and homozygotes who are deficient of the enzyme and should not receive the drug.

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

There is an increased risk of malignancy in humans with the use of purine antimetabolites for chronic immunosuppression. Reports of malignancy have included posttransplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. Healthcare providers using azathioprine should be very familiar with this risk, the mutagenic potential, and hematologic toxicities. Patients should be advised of the risk of malignancy with azathioprine.

Patients receiving immunosuppressants, including azathioprine, have an increased risk of developing lymphoma and other malignancies, predominantly of the skin. Patients with increased skin cancer risk should limit exposure to sunlight and ultraviolet light using protective clothing and high protection factor sunscreen. Renal transplant patients are reported to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. The risk of posttransplant lymphomas may be increased in patients who receive aggressive therapy with immunosuppressants; therefore, immunosuppressive drug therapy should be maintained at the lowest effective levels. Information is available on the malignancy risk in rheumatoid arthritis. It has not been possible to define the precise risk of malignancy due to azathioprine. The data suggest the risk may be increased in patients with rheumatoid arthritis, though lower than for renal transplant patients. However, acute myelogenous leukemia as well as solid tumors have been observed in patients with rheumatoid arthritis who have received azathioprine.

Use of azathioprine has been associated with development of HSTCL, primarily in adolescent and young adult males receiving treatment for Crohn's disease or ulcerative colitis. Most cases have occurred in patients receiving combination therapy known to suppress the immune system; however, there have been cases reported in patients receiving azathioprine alone. HSTCL is a fast-growing and usually fatal type of cancer. Patients should be monitored for the development of sign and symptoms of malignancies including splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss. Safety and efficacy of azathioprine have not been established for the treatment of Crohn's disease and ulcerative colitis.

Azathioprine is contraindicated for use in the treatment of rheumatoid arthritis in pregnant women. Azathioprine is contraindicated for use in patients with rheumatoid arthritis previously treated with alkylating agents (e.g., cyclophosphamide, chlorambucil, melphalan, or others) due to a prohibitive risk of malignancy.

Severe leukopenia, thrombocytopenia, anemias (including macrocytic anemia), and/or pancytopenia have been reported with azathioprine. Severe bone marrow suppression may be observed. Patients with intermediate thiopurine S-methyl transferase (TPMT) activity may be at an increased risk of myelotoxicity if receiving conventional doses of azathioprine. Patients with low or absent TPMT activity are at an increased risk of developing severe, life-threatening myelotoxicity if receiving conventional doses of azathioprine. TPMT phenotyping or genotyping can help identify patients who are at an increased risk for developing azathioprine toxicity. Hematologic toxicities are dose related and may present more severely in renal transplant patients undergoing organ rejection. It is suggested that patients on azathioprine have complete blood counts (CBC), including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are required. Delayed hematologic suppression may be observed. Prompt reduction in dosage or temporarily withdrawal of the drug may be required if there is a rapid fall in or persistently low leukocyte count, or other evidence of bone marrow depression. Leukopenia does not correlate with therapeutic effect; therefore the dose of azathioprine should not be increased intentionally to lower the white blood cell count.

It is advised that consideration be given to either genotype or phenotype patients for TPMT. Phenotyping and genotyping methods are commercially available. TPMT*2, TPMT*3A, and TPMT*3C are the most common nonfunctional alleles associated with reduced levels of TPMT activity. Patients with one nonfunctional allele (heterozygous) have intermediate activity and those with two nonfunctional alleles (homozygous) have low or absent TPMT activity. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have had recent blood transfusions. TPMT testing may also be considered in patients with abnormal CBC results that do not respond to dosage reduction. Early drug discontinuation in these patients is recommended. TPMT testing cannot substitute for CBC monitoring in patients receiving azathioprine therapy.

Patients receiving chronic immunosuppression, particularly homograft recipients, are at a higher risk for serious infections. Fungal, viral, bacterial, and protozoal infections may be fatal and should be treated aggressively. Reduction of azathioprine dosage and/or use of other drugs should be considered.

A gastrointestinal (GI) hypersensitivity reaction characterized by severe nausea and vomiting has been observed. These side effects may also be accompanied by diarrhea, rash, fever, malaise, myalgias, elevations in liver enzymes, and occasionally, hypotension. Symptoms of GI toxicity most often develop within the first several weeks of treatment with azathioprine and are reversible upon discontinuation of the drug. The event can recur within hours after rechallenge with a single dose of azathioprine.

All patients started on azathioprine should have CBC, including platelet count, weekly during the first month of treatment, twice monthly for the second and third months, then monthly or more frequently if dosage adjustments or other therapy changes are needed.

Dialysis

Hemodialysis, CAPD: The dose should be reduced to 50% of the normal daily dose.
Because azathioprine is moderately dialyzed by hemodialysis, doses should be administered after dialysis sessions.

Other Comments

Azathioprine is metabolized by thiopurine methyl transferase. In the general population, there are persons who are deficient of the enzyme, homozygotes (0.3%), and should not be given the drug, and there are persons with decrease enzyme activity, heterozygotes (10%), whose dose should be halved.

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