Echinocandins

GENERAL PRINCIPLES

This class of antifungals inhibits the enzyme (1,3)-#946;-d-glucan synthase that is essential in fungal cell wall synthesis.

TREATMENT

• 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.

Metabolism is primarily hepatic, although the CYP enzyme 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.

• Micafungin sodium (50-150 mg IV q24h) is used for candidemia, esophageal candidiasis, and as fungal prophylaxis for patients undergoing hematopoietic stem cell transplantation. 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.

• Anidulafungin (100-200 mg IV loading dose, followed by 50-100 mg IV q24h) is useful for treatment of candidemia and other systemic Candida infections (intra-abdominal abscess and peritonitis) as well as esophageal candidiasis. The spectrum of activity is similar to that of caspofungin and micafungin. Anidulafungin is not a substrate inhibitor or inducer of CYP isoenzymes and does not have clinically relevant drug interactions. No dosage change is necessary in renal or hepatic insufficiency.

SPECIAL CONSIDERATIONS

Adverse events: Fever, rash, nausea, elevated LFTs, histamine-related reactions, phlebitis at the injection site, and delirium are possible but infrequent adverse reactions.