Bone marrow depression azathioprine

Hematoiogic effects Severe leukopenia or thrombocytopenia, macrocytic anemia, severe bone marrow depression, and selective erythrocyte aplasia may occur in patients on azathioprine. Hematologic toxicities are dose-related, may occur late in the... 

Patients with frequent relapses despite apparently adequate prophylactic treatment should be reviewed carefully. Associated milk intolerance or coeliac disease need treatment on their merits. Colonoscopic evidence of dysplasia raises the question of undiagnosed malignancy. Occasionally the prophylactic agents themselves can cause watery diarrhoea (particularly olsalazine) or a hypersensitivity colitic disease. Prophylactic azathioprin should be considered in those in whom relapse is frequent despite use of aminosalicylates or if they are poorly tolerated. In the effective dose of 2 mg/kg adverse effects of bone marrow depression are uncommon, but still occur, and regular haematological review is essential (monthly or bi-monthly). Azathioprin-induced pancreatitis is an uncommon but well-recognised entity. 

Drug is less likely than azathioprine to induce severe bone marrow depression, and may replace azathioprine in conventional maintenance immunosuppression regimens... 

Dose-related toxicities of azathioprine or 6-mercaptopurine include nausea, vomiting, bone marrow depression (leading to leukopenia, macrocytosis, anemia, or thrombocytopenia), and hepatic toxicity. Routine laboratory monitoring with complete blood count and liver function tests is required. Leukopenia or elevations in liver chemistries usually respond to medication dose reduction. Severe leukopenia may predispose to opportunistic infections leukopenia may respond to therapy with granulocyte stimulating factor. Hypersensitivity reactions to azathioprine or 6-mercaptopurine occur in 5% of patients. These include fever, rash, pancreatitis, diarrhea, and hepatitis. 

Dosage An initial dose of azathioprine of 1—2 mg/kg BW/day (rounded off to the nearest 25 mg or 50 mg tablet) is recommended. A maintenance dose of 50-75 (—100) mg/day is sufficient. We always administered the combination therapy from the outset and thereby did not observe any side effects from azathioprine — minor fluctuations in bone-marrow depression reverted to normal values spontaneously or after a short period of reduced dosage (25 mg). With this maintenance dose, we retained a... 

The risk of bone marrow depression by cytostatic drugs is potentiated by allopurinol, which also appears to potentiate the therapeutic effect of purine cytostatic drugs, since it competitively inhibits their metabolic breakdown. Studies in animals suggest that this reaction occurs only with oral mercaptopurine (28), although there is older evidence that the toxicity of cyclophosphamide and other cytostatic drugs can be increased by allopurinol (SED-9, 156). The danger of combining allopurinol with azathioprine has been confirmed by cases of bone marrow suppression, particularly in patients with impaired renal function (SEDA-16,114). 

Azathioprine (Imuran) Converted to 6-mercaptopurine ribose phosphate which inhibits purine synthesis. Because DNA RNA synthesis requires proteins, all proliferating cells are inhibited (B-cells, T-cells, nonimmune cells). Prevention of organ transplant rejection. Gl distress, bone marrow depression, infections, mild leukopenia and thrombocytopenia. 

Yet another problem may be encountered in the treatment of patients in whom severe renal damage has developed prior to correct diagnosis, and applies too in both uric acid and 2,8-DHA stone formers. Here the allopurinol dose must be reduced because oxipuri-nol, the active metabolite in vivo, is reabsorbed by the kidney and retained in excess in renal failure. The effective circulating levels are thus higher and the dose must be reduced accordingly, and oxipurinol levels in plasma monitored if possible,with the dose adjusted to keep circulating levels below 100 /xmol/litre (14). Oxipurinol will not only potentiate the action of immunosuppressive drugs such as azathioprine but can itself produce severe bone marrow depression (14). 

Azathioprine is an effective agent in suppressing the immune system in patients undergoing renal transplantation and in patients suffering from acute glomerulonephritis, the renal component of systemic lupus erythematosus, prednisone-resistant idiopathic thrombocytopenic purpura, and functioning autoimmune hemolytic anemia. Azathioprine depresses bone marrow functioning, which is its chief side effect. 

Cytotoxic agents destroy immimologically competent cells. Azathioprine, a prodrug for the purine antagonist mercaptopurine, is used in autoimmune disease because it provides enhanced immunosuppressive activity. Cyclophosphamide is a second choice. Bone marrow is depressed as is to be expected. 

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