Fungal Infections


Micafungin (Mycamine, Astellas) was the second echinocandin to be licensed. It is a semi-synthetic modification of a fermentation product from the fungus Coleophoma empedri, the lead compound first reported in 1990. Initially reported in 1989, clinical studies of the efficacy of micafungin commenced in 1997, and it was licensed in Japan in 2002, in the USA in 2005 and in Europe in 2008. It inhibits the function of beta-(1,3)-D-glucan synthase.  

Dose & Delivery          

Micafungin is intravenous only. The standard dose is a 100mg, but doses up to 8mg/Kg have been given safely.

A  typical regimen:  For invasive or chronic aspergillosis, at least 150mg daily, for at least 2 weeks. Patients with mild or moderate liver insufficiency should receive the standard dose and it is possible that the drug is not appropriate for patients with severe liver disease. The appropriate dose in children is 2mg/Kg daily and 10mg/Kg in premature infants.

Fungi the drug is active against 

Micafungin is active against all species of Candida. It is extremely active and usually rapidly fungicidal against all species except Candida parapsilosis, Candida guilliermondii and Candida famata against which it is moderately active. Its in vitro activity appears to be greater than other echinocandins, but may be counterbalanced by its higher protein binding. It has activity against Candida biofilms, which azoles in general do not. Some resistant C. albicans, C. glabrata, C. tropicalis and C. krusei isolates have been described, almost all with mutations in 2 hot spots in the target gene.

Micafungin is also against all Aspergillus species. It is not fungicidal against Aspergilli. It is not antagonistic when given in combination with amphotericin B or azoles against Aspergilli.

Typical regimens          

For candidaemia, 100mg daily, increased to 150mg if neutropenic, for at least 2 weeks, or longer if candidaemia is slow to resolve.

For oesophageal candidiasis, 150mg daily, usually for 5-7 days.

For invasive aspergillosis, at least 150mg daily, for at least 2 weeks.

Metabolism and excretion        

The drug is metabolized in the body to several compounds (M1, M2 and M5 principally) some of which circulate. Exposure to these metabolites is low and they have no antifungal activity. No dose alterations need to be made in patients with organ dysfunction or taking other drugs with the one exception of severe liver dysfunction. Rapid clearance in premature infants (gestational age ~26 weeks) is approximately 5-fold greater than in adults, so much greater doses are required.

Drug/Drug interactions 

Micafungin has few interactions with cytochrome people P450 enzymes, so drug interactions are few. It is not a substrate for P-glycoprotein. Micafungin is highly bound to plasma protein (> 99%), more than any other echinocandin. Micafungin may increase the exposure to sirolimus, nifedipine or itraconazole. Micafungin increases amphotericin B exposure by ~30%. View drug interaction database.

Side effects      

Micafungin is well tolerated with occasional fever, phlebitis, headache, abdominal pain, nausea, diarrhoea, vomiting and rash. All were mild and/or reversible when the drug was stopped. Raised liver enzymes occur in up to 1 in 20 patients. Other side effects appeared to be rare.

Other information         

Long term side effects have not been established with the echinocandins because they are relatively new compounds. The duration of therapy is uncertain but typically should be at least two weeks beyond the last evidence of active disease unless a switch to another antifungal is made.

Structure of Micafungin


Coleophoma empedri, A pathogen of cranberry plants (image from Dr. Patricia McManus, University of Wisconsin-Madison) from which micafungin is fermented.

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