micafungin and Kidney-Diseases

Currently, three echinocandins are available for the treatment of fungal infections. Micafungin is the latest drug to be incorporated into this group of antifungal agents. Although the mechanism of action of micafungin is similar to that of other echinocandins, this molecule has certain pharmacokinetic characteristics that distinguish it from other drugs in this group. Nowadays, there is wide information on the pharmacokinetic behavior of micafungin, mainly from patients included in clinical trials. However, there is far less knowledge of the pharmacokinetics of this echinocandin in special populations. The aim of the current review was to analyze the available information on the pharmacokinetics of micafungin in pediatric patients, the elderly, patients with renal insufficiency or liver failure, and transplant recipient.

Topics: Adolescent; Adult; Age Factors; Aged; Antifungal Agents; Child; Child, Preschool; Clinical Trials as Topic; Comorbidity; Cytochrome P-450 CYP3A; Drug Interactions; Echinocandins; Humans; Infant; Kidney Diseases; Lipopeptides; Liver Diseases; Micafungin; Middle Aged; Mycoses; Postoperative Complications; Transplantation; Young Adult

Antifungal prophylaxis is the first option to fight against fungal infection in high-risk hematological patients (remission of induction of acute myeloblastic leukemia/myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation). Fluconazole prophylaxis is not effective in preventing infection with moulds, mainly invasive aspergillosis, and consequently the triazole currently recommended in high-risk hematological patients is posaconazole. Nevertheless, given that posaconazole can only be administered orally, alternative prophylaxis may be required. Antifungal prophylaxis with micafungin is an attractive option. At a dose of 50 mg/day (1 mg/kg if weight is ≤ 40 kg) micafungin is approved for the prophylaxis of candidiasis in hematopoietic stem cell transplant recipients. Higher doses have been evaluated in adults (100 mg/day, 150 mg/day) and in children (3 mg/kg/day) with good efficacy and safety. Because of this agent's spectrum of activity, which includes both Candida and Aspergillus, together with its favorable pharmacokinetic profile regarding to the absence of significant drug interactions, this agent is appropriate in hematopoietic stem cell transplant recipients and in hematological patients following therapeutic protocols with vinca alkaloids. The optimal and most cost-effective dose for prophylaxis, as well as alternative regimens to daily intravenous administration, which would allow the use of this drug beyond conventional hospitalization (day care hospital, domiciliary transplantation therapy), remain to be determined.

Topics: Adult; Ambulatory Care; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Male; Meta-Analysis as Topic; Micafungin; Mycoses; Postoperative Complications; Practice Guidelines as Topic; Triazoles

Less toxic antifungal drugs are required for empirical antifungal therapy. Micafungin is an echinocandin drug that is effective against both Candida and Aspergillus, and preliminary clinical studies have shown good antifungal activity. We prospectively examined the effect and safety of micafungin against febrile neutropenia with suspected fungal infection in 53 patients (median age, 56 years) who had undergone chemotherapy. The administered dose of micafungin was 150 mg/day, and its effect was evaluated as fever resolution as well as the results of chest imaging and serum fungal tests. Micafungin levels were measured on day 4 after the first administration using high-performance liquid chromatography. We also measured trough levels of micafungin. Underlying diseases comprised acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 20), multiple myeloma (n = 3), and non-Hodgkin's lymphoma (n = 26). The overall efficacy of micafungin was 70%. Breakthrough fungal infections were documented in two (3.8%) patients, both of whom died of invasive mycosis. None of the patients were switched to other antifungal drugs due to events unrelated to adverse effects. Plasma levels of micafungin and the degree of hepatic or renal dysfunction did not correlate. Micafungin is safe and effective for the empirical antifungal therapy of febrile neutropenia in patients with hematological malignancies.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Antineoplastic Agents; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Echinocandins; Female; Fever; Hematologic Neoplasms; Humans; Kidney Diseases; Lipopeptides; Liver Diseases; Male; Micafungin; Middle Aged; Mycoses; Neutropenia; Treatment Outcome

Micafungin is an antifungal agent metabolized by arylsulfatase with secondary metabolism by catechol-O-methyltransferase. The objectives of this study were to estimate the pharmacokinetic parameters and plasma protein binding of micafungin in volunteers with moderate hepatic dysfunction (n = 8), volunteers with creatinine clearance < 30 mL/min (n = 9), and matched controls (n = 8 and n = 9, respectively). Single-dose micafungin pharmacokinetics were estimated using noncompartmental techniques. There was a statistically lower area under the observed micafungin concentration-time curve (AUC) from time 0 to infinity for subjects with moderate hepatic dysfunction as compared to control subjects (97.5 +/- 19 microg.h/mL vs 125.9 +/- 26.4 microg.h/mL, P = .03), although there was no difference in micafungin weight-adjusted clearance (10.9 +/- 1.7 mL/h/kg vs 9.8 +/- 1.8 mL/h/kg, P = .2). The difference in area under the concentration-time curve may be explained by the differences in body weight between subjects and controls. Renal dysfunction did not alter micafungin pharmacokinetics.

Topics: Adult; Area Under Curve; Echinocandins; Female; Humans; Infusions, Intravenous; Kidney Diseases; Lipopeptides; Lipoproteins; Liver Diseases; Male; Metabolic Clearance Rate; Micafungin; Middle Aged; Peptides, Cyclic

Limited data exist regarding echinocandins as antifungal prophylaxis in liver transplant recipients.. The efficacy and safety of targeted prophylaxis with micafungin or amphotericin B lipid complex (ABLC) was assessed in a sequential cohort of high-risk patients (posttransplantation dialysis, retransplantation, or reoperation) and compared with those without high risk who did not receive prophylaxis. Outcomes were assessed at 90 days.. Micafungin versus ABLC recipients were older (P=0.0065) and more likely to have hepatocellular carcinoma (P=0.025). High-risks, that is, dialysis (55.6% vs. 79.2%), retransplantation (5.6% vs. 12.5%), and reoperation (38.9% vs. 20.8%) did not differ between the two groups. Invasive fungal infections developed in 11.1% (2 of 18) of micafungin recipients, 8.3% (2 of 24) of ABLC recipients, and 3% (7 of 234) of patients without high risks (P=0.12). In nondialyzed patients, ABLC versus micafungin recipients had significantly higher serum creatinine on day 14 (P=0.04). However, renal and hepatic function, rejection, graft loss, and mortality did not differ for the two groups on day 90.. Targeted prophylaxis with micafungin or ABLC decreased the risk of mycoses in high-risk recipients compared with that in low-risk recipients. Compared with ABLC, however, micafungin appeared to be associated with lower early-renal dysfunction and no additional risk of hepatic dysfunction.

Topics: Amphotericin B; Antifungal Agents; Chi-Square Distribution; Drug Administration Schedule; Echinocandins; Female; Graft Rejection; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Liver Transplantation; Male; Micafungin; Middle Aged; Mycoses; Premedication; Renal Dialysis; Reoperation; Risk Factors; Time Factors; Treatment Outcome

The echinocandins provide an attractive new option for prophylactic and empirical treatment of invasive fungal infections in patients with neutropenia after intensive cytotoxic chemotherapy or hematopoietic stem cell transplantation. We present two patients with hematological diseases who experienced massive intravascular hemolysis followed by renal failure after administration of micafungin. In indirect antiglobulin test, significant agglutination was observed when red blood cells were exposed to the mixture of micafungin and either of the patients' plasma samples, indicating that production of antibodies directed against both micafungin and red blood cell membrane induced hemolysis attack. Micafungin-mediated immune hemolysis represents an uncommon but life-threatening adverse reaction leading to renal failure.

Topics: Antibody Formation; Antifungal Agents; Echinocandins; Erythrocytes; Hemolysis; Humans; Kidney Diseases; Lipopeptides; Male; Micafungin; Middle Aged; Myelodysplastic Syndromes