Daptomycin Dosing: Once Daily (OD) Administration
Daptomycin is administered once daily (OD), never twice daily (BD), for all approved indications including complicated skin and soft tissue infections, bacteremia, and endocarditis. 1, 2
FDA-Approved Dosing Schedule
The FDA label explicitly specifies once-daily dosing for all indications 1:
- Complicated skin and skin structure infections (cSSSI): 4 mg/kg IV once daily 1, 2
- S. aureus bacteremia and right-sided endocarditis: 6 mg/kg IV once daily 1, 2
- Pediatric patients (1-17 years): Once daily dosing based on age-specific weight-based calculations 1
Pharmacokinetic Rationale for Once-Daily Dosing
Daptomycin exhibits concentration-dependent bactericidal activity, meaning efficacy is optimized by achieving high peak concentrations rather than maintaining continuous drug levels 3, 2:
- The key pharmacodynamic parameters are AUC₂₄/MIC ratio (target ≥250 for 80% kill efficacy) and Cmax/MIC ratio (target >10) 3, 2
- The elimination half-life is approximately 8 hours, supporting once-daily administration 4
- Plasma protein binding is 90-93% and remains stable across dosing ranges 4
Critical Safety Consideration: Why NOT Twice Daily
More frequent dosing intervals (such as BD) were associated with significantly increased skeletal muscle toxicity, including elevated creatine phosphokinase levels and myopathy 2. This is the primary reason daptomycin must be given once daily rather than divided doses.
Higher Dose Considerations
For severe infections, particularly endocarditis or infections with elevated MICs, higher once-daily doses may be warranted 3:
- 8-10 mg/kg once daily for complicated MRSA bacteremia and endocarditis 3
- 10-12 mg/kg once daily for multidrug-resistant enterococcal infections (off-label) 3
- Doses up to 12 mg/kg once daily have been studied and found safe in healthy volunteers 4
Renal Dosing Adjustment
For patients with creatinine clearance <30 mL/min or on hemodialysis, extend the dosing interval to once every 48 hours (not twice daily) 1, 2.
Common Pitfall to Avoid
Never divide the daily dose into twice-daily administration—this increases muscle toxicity risk without improving efficacy and contradicts the concentration-dependent pharmacodynamics that require high peak levels 2, 4.