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Severe leukopeniathrombocytopeniaanemias including macrocytic anemiaand/or pancytopenia may occur in patients being treated with IMURANSevere bone marrow suppression may also occurPatients with intermediate thiopurine S-methyl transferaseTPMTactivity may be at an increased risk of myelotoxicity if receiving conventional doses of IMURANPatients with low or absent TPMT activity are at an increased risk of developing severelife-threatening myelotoxicity if receiving conventional doses of IMURANTPMT genotyping or phenotyping can help identify patients who are at an increased risk for developing IMURAN toxicity2-9See PRECAUTIONSLaboratory TestsHematologic toxicities are dose-related and may be more severe in renal transplant patients whose homograft is undergoing rejectionIt is suggested that patients on IMURAN have complete blood countsincluding platelet countsweekly during the first monthtwice monthly for the second and third months of treatmentthen monthly or more frequently if dosage alterations or other therapy changes are necessaryDelayed hematologic suppression may occurPrompt reduction in dosage or temporary withdrawal of the drug may be necessary if there is a rapid fall in or persistently low leukocyte countor other evidence of bone marrow depressionLeukopenia does not correlate with therapeutic effecttherefore the dose should not be increased intentionally to lower the white blood cell count.
It has been suggested that the toxicity of Imuran may be enhanced in the presence of renal insufficiencybut controlled studies have not supported this suggestionNeverthelessit is recommended that the dosages used should be at the lower end of the normal range and that haematological response should be carefully monitoredDosage should be further reduced if haematological toxicity occurs.
Azathioprine suppresses disease manifestations as well as underlying pathology in animal models of autoimmune diseaseFor examplethe severity of adjuvant arthritis is reduced by azathioprine.
Patients receiving multiple immunosuppressive agents may be at risk of over-immunosuppressiontherefore such therapy should be maintained at the lowest effective level.
It has been suggested that cimetidine and indomethacin may have myelosuppressive effectswhich may be enhanced by concomitant administration of Imuran.
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