A New Antifungal With Fewer Limitations

[Guest guest]

Abstract: ph JM; Jain R; Danziger LH College of Pharmacy,

University of Illinois,

Chicago, Illinois

The echinocandins represent the newest class of antifungals to combat infections caused by Candida sp. Micafungin is an echinocandin

recently approved by the United States Food and Drug Administration. It is indicated in adults for esophageal candidiasis and prophylaxis against candidal

infections in hematopoietic stem cell transplant

recipients. Micafungin exhibits

in vitro fungicidal activity against Candida sp, including fluconazole-resistant

isolates. Its in vivo efficacy is comparable to that

of fluconazole in the treatment of esophageal candidiasis and superior to that of fluconazole

for prophylaxis of invasive candidal infections. Because it is not significantly metabolized by the cytochrome P450 3A system, micafungin

is associated with few drug interactions. Micafungin does not require adjustment in patients with

renal and/or hepatic impairment, and it has been shown to be well tolerated in

both adult and pediatric patients. Its efficacy

against Candida sp, coupled with its overall safety and drug interaction

profiles, makes it an attractive option in the treatment against esophageal candidiasis and prophylaxis against invasive candidal infections.

Study

Summary - Micafungin sodium (Mycamine) is

one of the latest in a class of echinocandin antifungals for fighting infections from Candida species. It

is indicated in adults for esophageal candidiasis and

is used as prophylaxis against candidal infections in

hematopoietic stem cell transplant recipients. Micafungin's in vivo efficacy is

comparable to that of fluconazole in the treatment of

esophageal candidiasis and surpasses that of fluconazole for prophylaxis of invasive candidal

infections. It is not significantly metabolized by the

cytochrome P450 3A system; therefore, it is

associated with few drug interactions. It also does

not require adjustment in patients with moderate renal and/or hepatic

impairment, and has been shown to be well tolerated in both adult and pediatric

patients.

The

recommended dosage of micafungin for the treatment of

esophageal candidiasis is 150 mg/day administered

intravenously over 1 hour. For patients undergoing hematopoietic stem cell transplantation, the recommended

prophylactic dose for candidal infections is 50

mg/day over 1 hour. A time-kill curve study

demonstrated that micafungin is primarily fungicidal

(greater than 99.9% reduction) against C albicans, C glabrata, and C

krusei, and fungistatic

against C tropicalis

isolates. The most common adverse events with micafungin include injection-site reactions such as

phlebitis, site irritation, and pain, along with histamine-related reactions of

pruritis, rash, and flushing.

Viewpoint

- This study found that dosages of micafungin do

not need to be adjusted for patients with moderate renal and/or hepatic

impairment (creatinine clearances of 15-29 mL/min and Child Pugh scores of 7-9), but it excluded

patients with severe hepatic disease from the study group. Therefore,

routine monitoring of liver function tests should be performed for patients

with severe hepatic dysfunction who are being given micafungin.

Traditional

antifungals -- amphotericin-based

formulas and azole agents -- are effective for

treating candidal infections, but they are also known

for their toxicities and drug interactions. Micafungin's efficacy against Candida species, along with its overall safety and drug

interaction profiles, make it an appealing option in the treatment of

esophageal candidiasis and prophylaxis against

invasive candidal infections.

Due to

the limited number of drug interactions associated with micafungin,

combination treatment is also possible. For instance,

the combination of micafungin with amphotericin or an azole agent

has been successful in case reports for salvage therapy against Aspergillus

species.[1]

Micafungin's mechanism of action

is similar to that of caspofungin, which is also in

the echinocandin class, and it is less expensive than

caspofungin based on the recommended treatment dose. However, because it is a new drug, further pharmacokinetic

studies are needed to evaluate potential drug interactions and to assess the

appropriate dosage parameters for patients with severe hepatic disease.

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