Azathioprine and Lisinopril: Interaction Details

a) Severe anemia developed in eleven renal transplant patients who had been switched from cyclosporine and prednisone to azathioprine and prednisone and were simultaneously receiving either captopril or enalapril ¹. In two of these patients, converting them back to cyclosporine led to rapid resolution of the anemia. To examine the impact of taking azathioprine together with either enalapril or captopril, two groups of 10 patients treated with azathioprine, one that also took an ACE inhibitor (group A) and one that did not (group B), were compared with respect to hematological parameters. Within group A, 8 patients were given enalapril and 2 were given captopril. The 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) levels in group A were significantly lower than those in group B. In group A, hematological parameters and renal function were assessed over the 3 to 6 months before and the 3 to 6 months after ACE inhibitor therapy was begun. A significant reduction in hematocrit (mean 41.5% vs 36%) and hemoglobin (mean 14.1% vs 11.3%) was observed 3 to 6 months after ACE inhibitor therapy was started. The remaining hematological parameters and renal function stayed stable. The combined use of azathioprine with either enalapril or captopril should be avoided.

b) A 37-year-old renal transplant patient became anemic during treatment with azathioprine and enalapril, even though recombinant human erythropoietin (rHuEpo) was also being given ². Three months after the transplant, enalapril 10 mg daily was added to the patient's therapy, which consisted of cyclosporine, azathioprine, mizoribine, and prednisolone. Normocytic normochromic anemia developed gradually, and 6000 International Units per week of rHuEpo was given intravenously once the hematocrit (Hct) fell from 38.7% to 21%. Even after the rHuEpo dose was raised to 9000 International Units, the anemia kept worsening. The patient showed no signs of declining renal function, leukopenia, or thrombocytopenia. Once the Hct dropped to 16.5%, enalapril was stopped. The Hct then gradually rose to 32.2%, despite the fact that rHuEpo administration had been discontinued.

c) A 17-year-old female with malignant nephrosclerosis had been successfully managed with captopril 50 mg daily and furosemide 500 mg daily for seven months. Her white cell counts remained within the normal range. She subsequently underwent a renal transplant, and 20 days after azathioprine 150 mg daily was added to the captopril therapy, the white cell count declined to 1700/mcgL. Azathioprine was discontinued and the white count returned to normal (4600/mcgL) within eight days. When azathioprine was restarted due to suspected rejection, the white count again dropped to 2300/mcgL over 16 days. Captopril therapy was stopped and blood pressure was managed with other antihypertensive drugs. The patient's white count normalized within five days (4700/mcgL), even though azathioprine therapy was continued ³.