By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
The FDA has approved a new intravenous antifungal agent. Micafungin is a member of the echinocandin class that inhibits the formation of fungal cell walls. It is the second member of the class after caspofungin. Micafungin is marketed by Fujisawa as MycamineTM.
Indications
Micafungin is indicated for the prophylaxis of Candida albicans infections in patients undergoing hematopoietic stem cell transplantation. It is also indicated for the treatment of patients with esophageal candidiasis.1
Dosage
The recommended dose for the treatment of esophageal candidiasis is 150 mg IV daily. The mean duration of treatment from clinical studies was 15 days (range, 10-30 days). For prophylaxis, the recommended dose is 50 mg per day with a mean duration of 19 days (range, 6-51 days).1
Intravenous infusion should be over a period of 1 hour. No dosage adjustment is required for severe renal or mild-to-moderate hepatic dysfunction.
Micafungin is available as 50 mg single-dose vials.
Potential Advantages
Micafungin (50 mg daily) has been shown to be more effective than fluconazole for prophylaxis of fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation (n = 882).2
Absence of invasive fungal infection occurred in 80% of patients in the micafungin arm and 73% in the fluconazole group. Micafungin is well tolerated and has a low potential for drug interactions,3,4 and is active against a broad range of Candida species including azole-resistant strains.4 Cross resistance to azole and amphotericin B has not been shown.3 Micafungin appears less likely to interact with cyclosporine than caspofungin resulting in elevation of liver enzymes.3
Potential Disadvantages
Micafungin is not available as an oral formulation. Patients receiving concomitant therapy with sirolimus or nifedipine should be monitored for toxicity due to increased bioavailability of these drugs.1 Adverse events associated with micafungin include leukopenia, neutropenia, nausea, vomiting, diarrhea, abdominal pain, rash, pyrexia, and rigor. The frequencies ranged from 1-3%.1 Elevations of liver enzymes, hyperbilirubinemia, and injection site reactions have also been reported.
Comments
Micafungin is the second member of the class, echinocandin. These drugs are inhibitors of -1.3-D-glucan synthase enzyme complex resulting in damaging fungal cell wall. It’s activity is mainly directed at Candida and Aspergillus spp. The minimum inhibitory concentration is lower than amphotericin B and fluconazole against common Candida spp.3 It’s generally fungicidal against Candida and fungistatic against Aspergillus spp. Phase III studies involved treating candidiasis and the prophylaxis of fungal infections in patients undergoing hematopoietic stem cell transplantation. Micafungin (50 mg daily) was found to be more effective than fluconazole (400 mg daily) in prophylaxis. For treatment of esophageal candidiasis micafungin in HIV-positive patients (150 mg daily) was comparable to fluconazole 200 mg daily (89.8% vs 86.7%).4 Micafungin is generally well tolerated and is at least as well tolerated as fluconazole. The wholesale cost of micafungin is $93.50 per 50 mg vial.
Clinical Implications
Current fluconazole is the standard for esophageal candidiasis and prophylaxis in neutropenic patients.5
Micafungin provides an effective alternative and appears to be more effective than fluconazole in prophylaxis in neutropenic patients. About 10% of Candida albicans and 48% of nonalbican spp. (eg, C. krusei, C. glabrata) are resistant to fluconazole and mycafungin may be an active option.4 The role of combination therapy (with amphotericin B or fluconasole) requires more study, but some degree of synergy has been reported.3,6 Caspofungin is also approved for esophageal candidiasis and has also shown comparable efficacy to fluconazole.7 However the role of this echinocandin is likely reserved for its other approved indications, candidemia and invasive aspergillosis refractory to or intolerant of other antifungal drugs.
References
1. Mycamine Product Information. Fujisawa Pharmaceutical Company. March 2005.
2. van Burik JH, et al. Clin Infect Dis. 2004;39: 1407-1416.
3. Denning DW. Lancet. 2003;362:1142-1151.
4. de Wet N, et al. Clin Infect Dis. 2004;39:842-849.
5. Bartlett JG. Pocket Book of Infectious Disease Therapy Lippincott Williams & Wilkins. Philadelphia, PA. 2004.
6. Jarvis B ,et al. Drugs. 2004;64:969-982.
7. Cancidas® Product Information. Merck & Co. Inc. March 2004.
The FDA has approved a new intravenous antifungal agent.
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