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TPMT TESTING CANNOT SUBSTITUTE FOR COMPLETE BLOOD COUNTCBCMONITORING IN PATIENTS RECEIVING IMURANTPMT genotyping or phenotyping can be used to identify patients with absent or reduced TPMT activityPatients with low or absent TPMT activity are at an increased risk of developing severelife-threatening myelotoxicity from IMURAN if conventional doses are givenPhysicians may consider alternative therapies for patients who have low or absent TPMT activityhomozygous for non-functional allelesIMURAN should be administered with caution to patients having one non-functional alleleheterozygouswho are at risk for reduced TPMT activity that may lead to toxicity if conventional doses are givenDosage reduction is recommended in patients with reduced TPMT activityEarly drug discontinuation may be considered in patients with abnormal CBC results that do not respond to dose reduction.

Chromosomal abnormalitieswhich disappear with timehave been demonstrated in lymphocytes from the offspring of patients treated with ImuranExcept in extremely rare casesno overt physical evidence of abnormality has been observed in the offspring of patients treated with ImuranAzathioprine and long-wave ultraviolet light have been shown to have a synergistic clastogenic effect in patients treated with azathioprine for a range of disorders.

Limited immunologic and other abnormalities have occurred in a few infants born of renal allograft recipients on IMURANIn a detailed case report13 documented lymphopeniadiminished IgG and IgM levelsCMV infectionand a decreased thymic shadow were noted in an infant born to a mother receiving 150 mg azathioprine and 30 mg prednisone daily throughout pregnancyAt 10 weeks most features were normalizedDeWitte et al reported pancytopenia and severe immune deficiency in a preterm infant whose mother received 125 mg azathioprine and 12.5 mg prednisone daily14 There have been two published reports of abnormal physical findingsWilliamson and Karp described an infant born with preaxial polydactyly whose mother received azathioprine 200 mg daily and prednisone 20 mg every other day during pregnancy15 Tallent et al described an infant with a large myelomeningocele in the upper lumbar regionbilateral dislocated hipsand bilateral talipes equinovarusThe father was on long-term azathioprine therapy16.

15Williamson RAKarp LEAzathioprine teratogenicityreview of the literature and case reportObstet Gynecol198158:247-250.

1Lennard LThe clinical pharmacology of 6-mercaptopurineEur J Clin Pharmacol1992;43:329-339.

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