title: Comedication of caspofungin acetate and cyclosporine A after allogeneic haematopoietic stem cell transplantation leads to negligible hepatotoxicity.
abstract: Infections and adverse drug reactions both contribute substantially to mortality after allogeneic stem cell transplantation. It is therefore crucial to the transplant physician to develop an optimal anti-infective strategy, i.e. one which is highly effective and shows few side effects. Caspofungin acetate, the founding member of the echinocandins, is widely used against invasive fungal infections. We retrospectively assessed the hepatotoxicity of caspofungin acetate when administered with cyclosporine A. We reviewed the medical charts of 20 recipients of an allogeneic transplant. In detail, the median value of alanine amino transferase before, during and after administration of caspofungin acetate was 0.39 [standard error of the mean (SEM) 0.65], 0.77 (17) and 0.56 (0.77) micromol l(-1). The maximal value was 4-, 104- and 3.3-fold the upper normal level. The median value of aspartate amino transferase was 0.28 (SEM 0.45), 0.71 (26.26) and 0.60 (0.84) micromol l(-1). The maximal value before, during and after the administration of caspofungin acetate was 3.6-, 203- and 5.3-fold the upper normal level. The median value of gamma glutamyl transferase before, during and after administration of caspofungin acetate was 1.27 (SEM 1.78), 2.33 (3.41) and 1.77 (4.32) micromol l(-1). The maximal value was 1.38-, 2.53- and 1.93-fold the upper normal level. The median value of alkaline phosphatase before, during and after administration of caspofungin acetate was 1.11 (SEM 0.4), 1.97 (2.30) and 1.66 (5.48) micromol l(-1). The maximal value was 0.88-, 4.2- and 8.42-fold the upper normal level, respectively. The median value of total bilirubin before, during and after administration of caspofungin acetate was 23 (SEM 19.69), 38 (55.41) and 20 (67.23) micromol l(-1). The maximal value was 4.18-, 14.18- and 17.88-fold the upper normal level. Taken together, the elevations observed fell after the discontinuation of caspofungin acetate. This report is in accordance with published data. As expected, we did not find any evidence pointing to an increase in nephrotoxicity by caspofungin acetate.
authors.affiliation: BMT Unit, Department of Internal Medicine IV, Oncology and Hematology, University Hospital Halle (Saale), Halle (Saale), Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Christopeit
authors.forename: Martin
authors.initials: M
authors.lastname: Eikam
authors.forename: Gerhard
authors.initials: G
authors.lastname: Behre
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077336:Caspofungin; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000503:physiopathology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005858:Germany; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D055666:Lipopeptides; D008297:Male; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D011183:Postoperative Complications / Q000188:drug therapy* / Q000517:prevention & control; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D016572:Cyclosporine; D000077336:Caspofungin