Benazepril and Azathioprine: Interaction Details

a) Eleven renal transplant patients who had been converted from cyclosporine and prednisone to azathioprine and prednisone and were concurrently taking either captopril or enalapril developed severe anemia ¹. When two of these patients were converted back to cyclosporine, their anemia rapidly resolved. In order to study the effect of concurrent use of azathioprine and either enalapril or captopril, two groups of 10 azathioprine-treated patients who did (group A) or did not (group B) take an ACE inhibitor were compared to determine hematological parameters. In group A, 8 patients received enalapril and 2 received captopril. Hematocrit (32.9 +/- 6.3% vs 41.0 +/- 5%), hemoglobin (11.5 +/- 2 g/dL vs 13.9 +/- 1.6 g/dL), and haptoglobin (115.7 +/- 65.4 vs 210.4 +/- 114.4 mg/dL) values of group A were significantly lower than those of group B. Hematological parameters and renal function were compared in group A for the periods 3 to 6 months before and 3 to 6 months after institution of ACE inhibitor therapy. There was a significant decrease in hematocrit (mean 41.5% vs 36%) and hemoglobin (mean 14.1% vs 11.3%) 3 to 6 months after starting ACE inhibitor therapy. Other hematological parameters and renal function remained stable. Concurrent use of azathioprine and either enalapril or captopril should be avoided.

b) A 37-year-old renal transplant patient developed anemia while being treated with azathioprine and enalapril, despite also receiving recombinant human erythropoietin (rHuEpo) ². Three months post-transplant, enalapril 10 mg daily was added to the patient's regimen, which included cyclosporine, azathioprine, mizoribine, and prednisolone. Normocytic normochromic anemia gradually appeared, and 6000 International Units per week of rHuEpo was administered intravenously when the hematocrit (Hct) dropped from 38.7% to 21%. In spite of the rHuEpo dose being increased to 9000 International Units, the anemia continued to worsen. The patient had no evidence of decreasing renal function, leukopenia, or thrombocytopenia. When the Hct dropped to 16.5%, the enalapril was discontinued. The Hct gradually recovered to 32.2%, even though the rHuEpo administration had been stopped.

c) A 17-year-old female with malignant nephrosclerosis was being successfully treated with captopril 50 mg daily and furosemide 500 mg daily for seven months. White cell counts were within the normal range. The patient then received a renal transplant, and 20 days after the addition of azathioprine 150 mg daily to the captopril therapy, the white cell count fell to 1700/mcgL. Azathioprine was stopped and the white count returned to normal (4600/mcgL) within eight days. When azathioprine was reintroduced because of suspected rejection, the white count again fell to 2300/mcgL over 16 days. Captopril therapy was discontinued and blood pressure was controlled by other antihypertensive medications. The patient's white count returned to normal within five days (4700/mcgL), despite continuing azathioprine therapy ³.