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This class of antifungals inhibits the enzyme (1,3)-β-D-glucan synthase that is essential in fungal cell wall synthesis.
- Caspofungin acetate (70 mg IV loading dose, followed by 50 mg IV q24h) has fungicidal activity against most Aspergillus and Candida spp., including azole-resistant Candida strains. Caspofungin does not have activity against Cryptococcus, Histoplasma, Blastomyces, Coccidioides, or Mucor spp. It is FDA approved for treatment of candidemia and refractory invasive aspergillosis and as empiric therapy in febrile neutropenia.
- Metabolism is primarily hepatic, although the cytochrome P450 system is not significantly involved. An increased maintenance dosage is necessary with the use of drugs that induce hepatic metabolism (e.g., efavirenz, nelfinavir, phenytoin, rifampin, carbamazepine, dexamethasone). The maintenance dose should be reduced to 35 mg for patients with moderate hepatic impairment; however, no dose adjustment is necessary for renal failure.
- In vitro and limited clinical data suggest a synergistic effect when caspofungin is given in conjunction with itraconazole, voriconazole, or amphotericin B for Aspergillus infections.
- Adverse events: Fever, rash, nausea, and phlebitis at the injection site are infrequent.
- Micafungin sodium is used for candidemia (100 mg IV q24h), esophageal candidiasis (150 mg IV q24h), and as fungal prophylaxis for patients undergoing hematopoietic stem cell transplantation (50 mg IV q24h). The spectrum of activity is similar to that of anidulafungin and caspofungin. There may be clinically insignificant increases in serum concentrations of sirolimus and nifedipine. Micafungin may increase cyclosporine concentrations in about 20% of patients. No change in dosing is necessary in renal or hepatic dysfunction.
- Adverse events include elevated LFTs and rare cases of rash and delirium.
- Anidulafungin (200 mg IV loading dose, followed by 100 mg IV q24h) is useful for treatment of candidemia and other systemic Candida infections (intra-abdominal abscess and peritonitis) as well as esophageal candidiasis (100-mg loading dose, followed by 50 mg daily). The spectrum of activity is similar to that of caspofungin and micafungin. Anidulafungin is not a substrate inhibitor or inducer of cytochrome P450 isoenzymes and does not have clinically relevant drug interactions. No dosage change is necessary in renal or hepatic insufficiency.
Adverse events include possible histamine-mediated reactions, elevations in LFTs, and, rarely, hypokalemia.