【药理作用】

Classification: Immunosuppressant

Action/Kinetics: Antimetabolite that is quickly split to form mercaptopurine. To be effective, the drug must be given during the induction period of the antibody response. The precise mechanism in depressing the immune response is unknown, but it suppresses cell-mediated hypersensitivities and alters antibody production. Inhibits synthesis of DNA, RNA, and proteins and may interfere with meiosis and cellular metabolism. The mechanism for its effect on autoimmune diseases is not known. Is readily absorbed from the GI tract. The anuric client manifests increased effectiveness and toxicity (up to twofold). Onset: 6-8 weeks for rheumatoid arthritis. t1/2: 3 hr.

【适应症】

As an adjunct to prevent rejection in renal homotransplantation. In adult clients meeting criteria for classic or definite rheumatoid arthritis as defined by the American Rheumatism Association. Restrict use to clients with severe, active, and erosive disease that is not responsive to conventional therapy. Investigational: Chronic ulcerative colitis, generalized myasthenia gravis, to control the progression of Behet's syndrome (especially eye disease), Crohn's disease (low doses).

【用法用量】

Tablets, IV Use in renal homotransplantation. Adults and children, initial: 3-5 mg/kg (120 mg/m2), 1-3 days before or on the day of transplantation; maintenance: 1-3 mg/kg (45 mg/m2) daily. Rheumatoid arthritis, SLE. Adults and children, tablets, initial: 1 mg/kg (50-100 mg); then, increase dose by 0.5 mg/kg/day after 6-8 weeks and thereafter q 4 weeks, up to maximum of 2.5 mg/kg/day; maintenance: lowest effective dose. Dosage should be reduced in clients with renal dysfunction. Myasthenia gravis. 2-3 mg/kg/day. However, side effects occur in more than 35% of clients. To control progression of Behet's syndrome. 2.5 mg/kg/day. To treat Crohn's disease. 75-100 mg/day.

【注意事项】

Pregnancy Category: D

Contraindications: Treatment of rheumatoid arthritis in pregnancy or in clients previously treated with alkylating agents. Pregnancy and lactation.

Special Concerns: Hematologic toxicity is dose-related and may occur late in the course of therapy; may be more severe in renal transplant clients undergoing rejection. Although used in children, safety and efficacy have not been established.

【不良反应】

Hematologic: Leukopenia, thrombocytopenia, macrocytic anemia, severe bone marrow depression selective erythrocyte aplasia. GI: N&V, diarrhea, abdominal pain, steatorrhea. CNS: Fever, malaise. Other: Increased risk of carcinoma severe infections (fungal, viral, bacterial, and protozoal), and hepatotoxicity are major side effects. Also, skin rashes, alopecia, myalgias, increase in liver enzymes, hypotension, negative nitrogen balance.

【相互作用】

ACE inhibitors / ↑ Risk of severe leukopenia Allopurinol / ↑ Pharmacologic effect of azathioprine R/T ↓ liver breakdown Anticoagulants / ↓ Anticoagulant effect Corticosteroids / With azathioprine, may cause muscle wasting after prolonged therapy Cyclosporine / ↑ Plasma cyclosporine levels Echinacea / Do not give with azathioprine Methotrexate / ↑ Plasma levels of the active metabolite, 6-mercaptopurine Tubocurarine / ↓ Tubocurarine effect and other nondepolarizing neuromuscular blocking agents

【药物过量】

Symptoms: Large doses may result in bone marrow hypoplasia bleeding, infection, and death. Treatment: Approximately 45% can be removed from the body following 8 hr of hemodialysis.