| Indication |
For use in the treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections, as well as esophageal candidiasis, and prophylaxis of Candida
infections in patients undergoing hematopoietic stem cell
transplantation. Micafungin is also used as an alternative for the
treatment of oropharyngeal candidiases and has been used with some
success as primary or salvage therapy, alone or in combination with
other antifungals, for the treatment of invasive aspergillosis. |
| Pharmacodynamics |
Formerly known as FK463, micafungin is a semisynthetic lipopeptide synthesized from a fermentation product of Coleophoma empetri
that works as an 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. Depending on its
concentration, micafungin may be fungicidal against some Candida, but is usually fungistatic against Apergillus.
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 beta-1,3-D-glucan, an
essential component of fungal cell walls which is not present in
mammalian cells. It does this by inhibiting beta-1,3-D-glucan synthase. |
| Absorption |
Not absorbed orally |
| Volume of distribution |
- 0.39 ± 0.11 L/kg [adult patients with esophageal candidiasis]
|
| Protein binding |
Highly (>99%) protein bound in vitro, independent of plasma
concentrations over the range of 10 to 100 µg/mL. The primary binding
protein is albumin; however, micafungin, at therapeutically relevant
concentrations, does not competitively displace bilirubin binding to
albumin. Micafungin also binds to a lesser extent to a1-acid-glycoprotein. |
| 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. |
| Route of elimination |
Fecal excretion is the major route of elimination (total radioactivity at 28 days was 71% of the administered dose). |
| Half life |
14-17 hours |
| Clearance |
- 0.359 +/- 0.179 mL/min/kg [Adult Patients with IC with 100 mg]
- 0.321 +/- 0.098 mL/min/kg [HIV- Positive Patients with EC with 50 mg]
- 0.327 +/- 0.093 mL/min/kg [HIV- Positive Patients with EC with 100 mg]
- 0.340 +/- 0.092 mL/min/kg [HIV- Positive Patients with EC with 150 mg]
- 0.214 +/- 0.031 mL/min/kg [hematopoietic stem cell transplant recipients 3 mg/kg]
- 0.204 +/- 0.036 mL/min/kg [hematopoietic stem cell transplant recipients 4 mg/kg]
- 0.224 +/- 0.064 mL/min/kg [hematopoietic stem cell transplant recipients 6 mg/kg]
- 0.223 +/- 0.081 mL/min/kg [hematopoietic stem cell transplant recipients 8 mg/kg]
|
| Toxicity |
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. |
