Cyclosporin A: drug discontinuation for the management of long-term toxicity after liver transplantation.
After liver transplantation, long-term cyclosporin A (CsA) administration is commonly complicated by renal insufficiency and other side effects. To manage these problems, 1.5 to 2.0 mg x kg(-1) x day(-1) of azathioprine for at least 6 weeks was prescribed; CsA was then discontinued or reduced to < or = 2.5 mg x kg(-1) x day(-1) for several months. The dose of prednisone was kept constant. CsA was discontinued in 14 patients because of nephrotoxicity (three or more serum creatinine levels of > or = 1.5 mg/dL), in 1 patient because of headaches and in 1 patient because of a generalized sensory neuropathy; 1 patient refused to continue taking the drug. The CsA dose was reduced in 13 patients, 12 because of nephrotoxicity and 1 because of headaches. One patient in whom administration of CsA was stopped developed azathioprine hepatotoxicity, whereas 1 patient whose dose was reduced developed acute cellular rejection. These complications were controlled by discontinuing azathioprine and reinitiating CsA. In the patients in whom CsA was discontinued, the mean serum creatinine level decreased from 2.42 +/- 0.48 to 1.72 +/- 0.39 mg/dL (P = .00004); in the patients in whom CsA was reduced, the mean serum creatinine level decreased less markedly. This report suggests that discontinuation of CsA along with increased doses of azathioprine is safe for some patients and may be effective in managing CsA-related nephrotoxicity and other side effects after liver transplantation. Additional studies are needed to determine whether this approach is safe and effective for the growing number of post-transplantation patients who may be candidates for such therapy.
Liver Study Unit, Department of Medicine, University of Chicago, IL, USA.
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Chan
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DasGupta
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Baker
D000328:Adult; D001379:Azathioprine / Q000494:pharmacology; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine