Azathioprine

Indications

Azathioprine is used for: Rheumatoid arthritis, Prevention of rejection in organ and tissue transplantation, Auto-immune diseases, Renal homotransplantation

Adult Dose

Rheumatoid Arthritis 1 mg/kg/day 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 Kidney Transplantation Prevention of transplant rejection 3-5 mg/kg/day PO initially on day of transplant or 3 days before transplant (rare) Maintenance: 1-3 mg/kg/day PO Auto-immune diseases 1-3 mg/kg/day. Hepatic Impairment Reduce dose.

Child Dose

Juvenile Idiopathic Arthritis 1 mg/kg/day 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

Renal Dose

Reduce dose.

Administration

May be taken with or without food. Preferably taken w/ or after meals to reduce GI discomfort.

Contra Indications

Hypersensitivity; previous treatment with alkylating agents; pregnancy, lactation.

Precautions

Increased risk of serious infections and neoplasia in chronic immunosuppression; leucopenia, thrombocytopenia, renal or hepatic impairment. Increased risk of haematologic toxicity in patients with thiopurine methyltransferase deficiency. Monitor CBC (including platelet count) wkly during 1st mth, twice mthly for 2nd and 3rd mth, then mthly; monitor more frequently if there are dosage adjustments. Monitor LFT periodically; discontinue treatment if jaundice occurs. Reduce dose promptly or withdraw drug temporary if there is rapid decrease/persistently low WBC or signs of bone marrow depression. Dose reduction may be necessary in patients with reduced TPMT (thiopurine methyltransferase) activity. Lactation: Drug excreted at low levels in breast milk; use not recommended

Pregnancy-Lactation

Pregnancy category: D Lactation: Drug excreted at low levels in breast milk; use not recommended

Interactions

Increased risk of haematotoxicity with aminosalicylates, drugs that affect myelopoesis e.g. co-trimoxazole or trimethoprim. Increased risk of infections with intra-uterine devices and live vaccines. Increased risk of leucopenia with ACE inhibitors. Concurrent use may reduce the anticoagulant effect of vitamin K antagonists e.g. warfarin. Increased risk of myelosuppressive effects when used with drugs that inhibit TPMT (thiopurine methyltransferase) or xanthine oxidase e.g. olsalazine, allopurinol. Potentially Fatal: Increased risk of serious haematotoxicity or hepatotoxicity with leflunomide. Increased risk of bone marrow suppression with mycophenolate mofetil. Increased risk of infections and malignancies with efalizumab.

Adverse Effects

Side effects of Azathioprine : >10% Leukopenia (28-50%), Infection (20%) <1% Lymphoma Frequency Not Defined Fever, chills; bone marrow depression, thrombocytopenia or anaemia; anorexia, nausea, diarrhoea; arthralgias; secondary infections; hepatotoxicity, rash, alopoecia. Potentially Fatal: Myelosuppression, mutagenicity and carcinogenicity; veno-occlussive liver disease.

Mechanism of Action

Azathioprine is an imidazolyl derivative of mercaptopurine, which inhibits DNA, RNA and protein synthesis and antagonises purine synthesis. It also inhibits mitosis and interferes with cellular metabolism of susceptible organisms. Azathioprine inj should be converted to oral therapy as soon as the drug can be tolerated.