The Food and Drug Administration (FDA) recently approved Cubicin[TM] (daptomycin for injection) for the treatment of complicated skin and skin structure infections. Cubicin is the first approved product in a new class of antibiotics called cyclic lipopeptide antibacterial agents. The mechanism of action of daptomycin is distinct from any other antibiotic. Daptomycin binds to bacterial membranes and causes a rapid depolarization of membrane potential. The loss of membrane potential leads to inhibition of protein, DNA, and RNA synthesis, which results in bacterial cell death.
Cubicin has been shown to be effective against susceptible strains of the following Gram-positive microorganisms): Staphylococcus aureus (including methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp, equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only). Cubicin is not indicated for the treatment of pneumonia.
The recommended dosing schedule for Cubicin is 4 mg/kg/day IV infusion. Doses of Cubicin higher than 4 mg/kg/day have not been studied in Phase 3 controlled clinical trials. In Phase 1 and 2 clinical studies, CPK elevations appeared to be more frequent when daptomycin was dosed more frequently than once daily. Daptomycin is excreted primarily by the kidney and lower doses should be given to patients with renal impairment. No dosage adjustment is warranted when administering daptomycin to patients with mild to moderate hepatic impairment. The pharmacokinetics of daptomycin in patients with severe hepatic insufficiency have not been evaluated. In vitro studies with human hepatocytes indicate that daptomycin does not inhibit or induce the activities of the following human cytochrome (CYP) P450 isoforms: IA2, 2A6, 2C9, 2C19, 2D6, 2El, and 3A4. It is unlikely that daptomycin will inhibit or induce the metabolism of drugs metabolized by the CYP P450 system.
The most common adverse events included gastrointestinal disorders, injection site reactions, fever, headache, insomnia, dizziness, and rash. Few patients developed elevations in serum CPK levels.
Cubist Pharmaceuticals, Inc. is the sponsor of the New Drug Application (NDA) for Cubicin.
COPYRIGHT 2003 Journal of Drugs in Dermatology
COPYRIGHT 2004 Gale Group
Contact
Home
A
Dacarbazine