Authors: Carter, Natalie J.; Keating, Gillian M.

Source: Pediatric Drugs, Volume 11, Number 4, 4 August 2009 , pp. 271-291(21)

Publisher: Adis International

Abstract:

Abstract Intravenous micafungin (Mycamine®; Funguard®) is an echinocandin indicated in Japan and the EU for the treatment of pediatric patients (including neonates) with invasive candidiasis and as prophylaxis against Candida infection in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the EU, micafungin is also indicated in pediatric patients who are expected to have neutropenia for ≥10 days. In Japan, children may also receive micafungin for the treatment of, or as prophylaxis against, invasive Aspergillus infection. Micafungin is not currently approved for use in pediatric patients in the US.

Micafungin has very good antifungal activity against a wide range of Candida spp. in vitro. It has a favorable pharmacokinetic profile allowing for once-daily administration, has few drug-drug interactions, and reports of resistance are rare. The results of pediatric substudies indicate that intravenous micafungin is effective in a majority of patients for the treatment of candidemia and other types of invasive candidiasis, and provides effective prophylaxis against invasive fungal infections in pediatric patients undergoing HSCT. The tolerability profile of micafungin in pediatric patients was generally acceptable. In the EU, micafungin is indicated for use when other antifungal medications are not appropriate. Therefore, micafungin provides an alternative to other antifungal agents used in the management of candidemia and invasive candidiasis in pediatric patients, or as prophylaxis against fungal infections in pediatric patients undergoing HSCT.

Pharmacologic Properties Micafungin inhibits the synthesis of 1,3-β-D-glucan, a major component of fungal cell walls. It has demonstrated in vitro antifungal and fungicidal activity against a wide range of Candida spp. encountered clinically, including multidrug-resistant Candida spp. residing in biofilms, and fluconazole-resistant Candida spp. In two large (n >1000 clinical isolates) studies, the minimum inhibitory concentration at which 90% of isolates were inhibited (MIC₉₀) was 0.015-0.06 μg/mL for C. albicans, C. glabrata, C. kefyr, and C. tropicalis isolates. In the larger of the two studies, the micafungin MIC₉₀ was 0.015-2 μg/mL across all Candida spp. isolates, and 100% susceptibility to micafungin was seen at an MIC of 0.06-2 μg/mL, depending on the isolate. An MIC susceptibility breakpoint for micafungin against Candida spp. of ≤2 μg/mL was recently established by the Clinical and Laboratory Standards Institute. Reports of resistance to micafungin are rare.

Because of its high molecular weight, micafungin has poor oral bioavailability and is only available for intravenous administration. Over a dose range of 0.5-6.0 mg/kg, micafungin demonstrated linear, dose-proportional pharmacokinetics in pediatric patients with febrile neutropenia or deep mycosis and in premature neonates with a variety of underlying conditions. Micafungin is >99% plasma protein bound. It is mainly metabolized in the liver and is predominantly excreted via the fecal route. The clearance of micafungin was affected by age, with patients aged 2-8 years clearing the drug more quickly than those aged 9-17 years. Micafungin had few drug-drug interactions.

Therapeutic Efficacy Intravenous micafungin was effective in the treatment of pediatric patients aged <16 years (including neonates) with candidemia or other types of invasive candidiasis in a pediatric substudy (n = 109) of a large (n = 537), randomized, double-blind, multicenter, phase III trial. In this substudy, the efficacy of micafungin 2 mg/kg/day in patients weighing ≤40 kg and 100 mg/day in those weighing >40 kg was compared with that of liposomal amphotericin B 3 mg/kg/day; all medications were infused over 1 hour each day for 2-8 weeks. Candidemia accounted for over 90% of infections in this study, and a non-C. albicans spp. was the infecting organism in ≈60% of cases. Micafungin was effective in the majority of patients for the treatment of candidemia or other types of invasive candidiasis, irrespective of patient age, primary diagnosis, baseline neutropenic status, and whether or not the patient required an increase in drug dosage, was born prematurely, or had an intravenous catheter present at baseline. With regard to the primary endpoint, 73% and 76% of micafungin and liposomal amphotericin B recipients achieved treatment success (i.e. clinical and mycologic response) at the end of treatment (EOT) as determined by the study investigator.

Document Type: Research article

Affiliations: 1: Wolters Kluwer Health ∣ Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Philadelphia, Pennsylvania, USA

Publication date: 2009-08-04

Related content

• In this: publication
• By this: publisher
• In this Subject: Pediatrics ,  Pharmacology
• By this author: Carter, Natalie J. ;  Keating, Gillian M.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers