s treated with CUBICIN in the Phase 3 controlled clinical trial of S. aureus bacteremia/endocarditis, 25% were 65 years of age or older and 16% were 75 years of age or older. In Phase 3 clinical trials of cSSSI and S. aureus bacteremia/endocarditis, clinical success rates were lower in patients ≥65 years of age than in patients <65 years of age. In addition, treatment-emergent adverse events were more common in patients ≥65 years of age than in patients <65 years of age.
The exposure of daptomycin was higher in healthy elderly subjects than in healthy young subjects. However, no adjustment of CUBICIN dosage is warranted for elderly patients with creatinine clearance (CL) ≥30 mL/min [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ].
Daptomycin is eliminated primarily by the kidneys; therefore, a modification of CUBICIN dosage is recommended for patients with CL <30 mL/min, including patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). In patients with renal impairment, both renal function and creatine phosphokinase (CPK) should be monitored more frequently than once weekly [see Dosage and Administration (2.4) , Warnings and Precautions (5.2, 5.7), and Clinical Pharmacology (12.3) ].
In the event of overdosage, supportive care is advised with maintenance of glomerular filtration. Daptomycin is cleared slowly from the body by hemodialysis (approximately 15% of the administered dose is removed over 4 hours) and by peritoneal dialysis (approximately 11% of the administered dose is removed over 48 hours). The use of high-flux dialysis membranes during 4 hours of hemodialysis may increase the percentage of dose removed compared with that removed by low-flux membranes.
CUBICIN contains daptomycin, a cyclic lipopeptide antibacterial agent derived from the fermentation of Streptomyces roseosporus. The chemical name is N-decanoyl-L-tryptophyl-D-asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε-lactone. The chemical structure is:
The empirical formula is CHNO; the molecular weight is 1620.67. CUBICIN is supplied in a single-use vial as a sterile, preservative-free, pale yellow to light brown, lyophilized cake containing approximately 500 mg of daptomycin for intravenous (IV) use following reconstitution with 0.9% sodium chloride injection [see Dosage and Administration (2.5) ]. The only inactive ingredient is sodium hydroxide, which is used in minimal quantities for pH adjustment. Freshly reconstituted solutions of CUBICIN range in color from pale yellow to light brown.
Daptomycin is an antibacterial drug [see Microbiology (12.4) ].
Based on animal models of infection, the antimicrobial activity of daptomycin appears to correlate with the AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio for certain pathogens, including S. aureus. The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in
Manufacturer
Cubist Pharmaceuticals, Inc.
Active Ingredients
Source
U.S. National Library of Medicine
DailyMed
Last Updated: 2nd of March 2011
