Uses
An echinocandin antifungal drug which inhibits the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections.
Uses
Micafungin is a semi-synthetic cyclic lipopeptide belonging to the echinocandin class that was reported in 1999 from Fujisawa in Japan. Unlike other marketed semi-synthetic derivatives in this class, micafungin is not derived from echinocandin but rather from FR901379 which contains a phenolic sulfate to enhance aqueous solubility, a serious limitation in the class. Micafungin inhibits the synthesis of β-(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi and is extensively referenced in the literature with over 700 citations.
Uses
Micafungin is a semi-synthetic cyclic lipopeptide belonging to the echinocandin class that was reported in 1999 from Fujisawa in Japan. Unlike other marketed semi-synthetic derivatives in this class, micafungin is not derived from echinocandin but rather from FR901379 which contains a phenolic sulphate to enhance aqueous solubility, a serious limitation in the class. Micafungin inhibits the synthesis of β-(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi and is extensively referenced in the literature with over 700 citations.
Definition
ChEBI: A cyclic hexapeptide echinocandin antibiotic which exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall. It is used as the sodium salt for the treatment of invas
ve candidiasis, and of aspergillosis in patients who are intolerant of other therapy.
Originator
Fujisawa (Japan)
Brand name
Mycamine(Astellas);Funguard.
Antimicrobial activity
It is active against Aspergillus spp., Candida spp. and the cyst
form of Pn. jirovecii. Resistance has rarely been reported.
Pharmaceutical Applications
A semisynthetic lipopeptide derived from a fermentation
product of Coleophoma empetri. Formulated as the monosodium
salt for intravenous infusion.
Pharmacokinetics
Cmax 50 mg 1-h infusion: c. 5 mg/L 1 h post infusion
Plasma half-life: 11–15 h
Volume of distribution: 0.4 L/kg
Plasma protein binding: 99%
Blood concentrations increase in proportion to dosage. Unlike anidulafungin and caspofungin, a loading dose is not required.
Distribution
The drug is widely distributed, the highest concentrations being found in the liver. Levels in the CSF and urine are negligible.
Metabolism and excretion
It is metabolized by the liver and the three inactive metabolites are excreted in the feces (70%). Less than 1% of a dose is eliminated as unchanged drug in the urine. No dosage adjustment is required in patients with severe renal impairment or mild to moderate hepatic impairment. The effect of severe hepatic impairment on micafungin pharmacokinetics has not been studied. Micafungin is not cleared by hemodialysis.
Clinical Use
Candidemia and certain invasive forms of candidosis
Esophageal candidosis
Prophylaxis of Candida infections in hematopoietic stem cell transplant
(HSCT) recipients
Side effects
Occasional histamine-mediated infusion-related reactions,
injection site reactions and transient abnormalities of liver
enzymes have been reported. Isolated cases of significant
hepatic or renal dysfunction, hepatitis, or liver or renal failure
have also been described.
Drug interactions
Potentially hazardous interactions with other drugs
Ciclosporin: possibly increases ciclosporin
concentration.
Sirolimus: increases sirolimus concentration.
Metabolism
Metabolised in the liver by arylsulfatase to its catechol
form and further metabolised to the methoxy form by
catechol-O-methyltransferase. Some hydroxylation to
micafungin via cytochrome P450 isoenzymes also occurs.
Exposure to these metabolites is low and metabolites do
not contribute to the overall efficacy of micafungin.
After 28 days about 71% of a dose is recovered in the
faeces and 12% in the urine.
