Brands, Medical Use, Clinical Data
- Powder for solution (for injection)
Brands / Synonyms
For use in the treatment of patients with esophageal candidiasis and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation.
Formerly known as FK463, micafungin is a novel antifungal agent. It is a glucan synthesis inhibitor of the echinocandin structural class. The U.S. Food and Drug Administration approved micafungin in March 2005. Micafungin inhibits an enzyme essential for fungal cell-wall synthesis and is fungicidal (lethal) for Candida. Micafungin can be used concomitantly with a variety of other drugs, including the HIV protease inhibitor ritonavir and the transplant medications cyclosporine and tacrolimus.
Mechanism of Action
Micafungin inhibits the synthesis of 1,3-b-D-glucan, an essential component of fungal cell walls, which is not present in mammalian cells.
Intravenous LD50 in rats is 125mg/kg. In dogs it is >200mg/kg. No cases of overdosage have been reported. Repeated daily doses up to 8 mg/kg (maximum total dose of 896 mg) in adult patients have been administered in clinical trials with no reported dose-limiting toxicity. The minimum lethal dose is 125 mg/kg in rats, equivalent to 8.1 times the recommended human clinical dose for esophageal candidiasis based on body surface area comparisons.
Biotrnasformation / Drug Metabolism
Micafungin is metabolized to M-1 (catechol form) by arylsulfatase, with further metabolism to M-2 (methoxy form) by catechol-O-methyltransferase. M-5 is formed by hydroxylation at the side chain (w-1 position) of micafungin catalyzed by cytochrome P450 (CYP) isozymes. Even though micafungin is a substrate for and a weak inhibitor of CYP3A in vitro, hydroxylation by CYP3A is not a major pathway for micafungin metabolism in vivo.
MYCAMINE is contraindicated in patients with hypersensitivity to any component of this product.
A total of 11 clinical drug-drug interaction studies were conducted in healthy volunteers to evaluate the
potential for interaction between MYCAMINE and mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone,
sirolimus, nifedipine, fluconazole, ritonavir, and rifampin. In these studies, no interaction that altered the
pharmacokinetics of micafungin was observed.
There was no effect of a single dose or multiple doses of MYCAMINE on mycophenolate mofetil, cyclosporine,
tacrolimus, prednisolone, and fluconazole pharmacokinetics.
Sirolimus AUC was increased by 21% with no effect on Cmax in the presence of steady-state MYCAMINE
compared with sirolimus alone. Nifedipine AUC and Cmax were increased by 18% and 42%, respectively, in the
presence of steady-state MYCAMINE compared with nifedipine alone. Patients receiving sirolimus or nifedipine in
combination with MYCAMINE should be monitored for sirolimus or nifedipine toxicity and sirolimus or nifedipine dosage
should be reduced if necessary.
Micafungin is not an inhibitor of P-glycoprotein and, therefore, would not be expected to alter
P-glycoprotein-mediated drug transport activity.