micafungin and Liver-Failure

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.

Topics: Actins; Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Area Under Curve; Candidiasis; Caspofungin; Drug Resistance, Microbial; Echinocandins; Humans; Lipopeptides; Lipoproteins; Liver; Liver Failure; Micafungin; Models, Chemical; Peptides, Cyclic; Rats

One of the major adverse events of caspofungin and micafungin is hepatotoxicity, however, there are few reports compared the incidence of hepatotoxicity between caspofungin and micafungin. Herein, the primary objective of this study was to compare the incidence of hepatotoxicity between caspofungin and micafungin treatments for patients with fungal or suspected fungal infection.. In total, 201 patients [caspofungin group: 66 patients; micafungin group: 135 patients] treated with echinocandins from April 2014 to November 2015 at Aichi Medical University Hospital. Investigation item were as follows; sex, age, weight, height, duration of treatment, total dose, disease type, clinical isolates, liver enzyme levels, concomitant medications. Liver function was assessed in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. We divided into two groups depend on their liver enzyme levels before treated with echinocandins; normal group (liver enzyme levels ≤ CTCAE Grade 1), abnormal group (liver enzyme levels ≥ CTCAE Grade 2).. The overall incidence of serious hepatotoxicity (Grade 3 or higher) was 6.1% (4/66) in the caspofungin group and 7.4% (10/135) in the micafungin group. The proportion of patients used caspofungin and micafungin showed serious hepatotoxicity were 0% (0/47) and 6.5% (7/108) in normal group (p = 0.17), and 21.1% (4/19) and 10.7% (3/28) in abnormal group (p = 0.42).. There was no notable difference in serious hepatotoxicity between the caspofungin group and the micafungin group, even though in patients with abnormal liver enzyme levels (CTCAE grade 2 or higher).

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Caspofungin; Echinocandins; Female; Humans; Incidence; Lipopeptides; Liver Failure; Male; Micafungin; Middle Aged; Mycoses; Retrospective Studies; Young Adult

To determine the reasons of prescription, the characteristics of patients and factors that affected the outcome of critically ill patients treated with micafungin (MCF) during their stay in Spanish ICUs.. Observational, retrospective and multicenter study. Patients admitted to the ICU between March 2011 and October 2012 (20-month period) treated with MCF for any reason were included in the study. Severity of patients at the beginning of treatment was measured with the APACHE II, SOFA, Child-Pugh and MELD scores. Reasons for the use of MCF were classified as prophylaxis, preemptive treatment, empirical treatment and directed treatment. Continuous variables are expressed as mean and standard deviation or median, and categorical variables as percentages. A multivariate analysis was performed to identify variables related to intra-ICU mortality.. The study population included 139 patients admitted to 19 Spanish ICUs, with a mean age of 57.3 (17.1) years, 89 (64%) men, with surgical (53.2%) and/or medical (44.6%) conditions, APACHE II score of 20.6 (7.7) and SOFA score of 8.4 (4.3), with 84.2% of patients requiring mechanical ventilation, 59% parenteral nutrition, 37.4% extrarenal depuration procedures and 37.4% treatment with steroids. MCF was indicated as empirical treatment of a proven infection in 51 (36.7%) cases, pre-emptive treatment in 50 (36%) especially as a result of the application of the Candida score (32 cases), directed treatment of fungal infection in 23 (16.5%) and as prophylactic treatment in 15 (10.8%) cases. In 108 (77%) cases, a daily dose of 100mg was administered, with a loading dose in only 9 cases (6.5%). The mean duration of treatment was 13.1 (13) days. A total of 59 (42.4%) patients died during their stay in the ICU and 16 after ICU discharge (hospital mortality 53.9%). Independent risk factors for intra-ICU mortality were the Child-Pugh score (OR 1.45, 95% CI 1.162-1.813; P=.001) and the MELD score (OR 1.05, 95% CI 1.011-1.099; P=.014).. MCF is usually administered at a dose of 100mg/day, without loading dose and in 72.7% of cases as pre-emptive or empirical treatment. Factors that better predicted mortality were indicators of liver insufficiency at the time of starting treatment.

Topics: Adult; Aged; Antifungal Agents; Combined Modality Therapy; Critical Care; Echinocandins; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Lipopeptides; Liver Failure; Male; Micafungin; Middle Aged; Mycoses; Postoperative Complications; Retrospective Studies; Severity of Illness Index; Spain

Topics: Antifungal Agents; Candidiasis; Double-Blind Method; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Echinocandins; Europe; Humans; Lipopeptides; Liver Failure; Micafungin; Randomized Controlled Trials as Topic