Caspofungin, a new weapon against invasive aspergillosis

Caspofungin (MK-0991; L-743,872; CASPOFUNGIN MSD(R)) is a member of the echinocandin family, a new class of antifungal agents acting on the fungus wall by inhibiting the synthesis of glucan. In vitro, caspofungin is active against yeasts of the genus Candida, on several species of filamentous fungi including Aspergillus spp. as well as some dimorphic fungi. Several experimental studies in immunosuppressed or neutropenic mice and rats have shown that caspofungin is effective against invasive aspergillosis when given intraperitoneally. The poor bioavailability of caspofungin following oral administration means that it has to be given intravenously. Its half-life elimination is long (9 to 11 hours) which means that it can be given once daily. No decrease in daily dose is required in patients with renal or mild hepatic impairment. In humans, the efficacy of intravenous caspofungin (70 mg on the first day, then 50 mg/d thereafter) has been shown in the second-line treatment of invasive aspergillosis in patients resistant to, or unable to tolerate, standard treatment. A favorable response (complete or partial) was seen in 26 (41%) of the 63 evaluable patients. Overall, the safety profile of caspofungin at a dose of 50 mg/d or over, studied in over 400 patients, is good. The most common side-effects are fever, irritation at the site of infusion, headache or nausea. Renal tolerability is excellent. A few cases of transient elevation of transaminases have been reported especially during the concomitant administration of ciclosporine.