Daptomycin IV Dosing for Adults
The FDA-approved dose of daptomycin is 4 mg/kg IV once daily for complicated skin and soft tissue infections and 6 mg/kg IV once daily for S. aureus bacteremia and right-sided endocarditis, though expert consensus supports higher doses of 8-10 mg/kg for complicated infections including left-sided endocarditis. 1
Standard FDA-Approved Dosing
Complicated Skin and Soft Tissue Infections (cSSSI)
- 4 mg/kg IV once every 24 hours for 7-14 days 1
- Can be administered as either a 2-minute IV push or 30-minute infusion in adults 1
S. aureus Bacteremia and Right-Sided Endocarditis
- 6 mg/kg IV once every 24 hours for 2-6 weeks 1
- This is the only FDA-approved dose for bloodstream infections 2
- Duration depends on complexity: 2 weeks for uncomplicated bacteremia, 4-6 weeks for complicated bacteremia or endocarditis 2
Expert-Recommended Higher Dosing (Off-Label)
Left-Sided Endocarditis and Complicated Infections
- 8-10 mg/kg IV once daily is recommended by multiple expert guidelines for left-sided endocarditis and complicated MRSA infections 2
- The American Heart Association explicitly notes that while these higher doses are not FDA-approved, they may reduce treatment-emergent resistance and are generally well tolerated 2
- Infectious diseases consultation should guide selection of higher dosing 2
Enterococcal Endocarditis (Multidrug-Resistant)
- 10-12 mg/kg IV once daily for penicillin-, aminoglycoside-, and vancomycin-resistant enterococci 3
- Treatment duration exceeds 6 weeks for these resistant organisms 3
Renal Dosing Adjustments
Creatinine Clearance ≥30 mL/min
- No adjustment needed - use standard dosing every 24 hours 1
Creatinine Clearance <30 mL/min (Including Hemodialysis)
- Administer every 48 hours instead of every 24 hours 1
- For cSSSI: 4 mg/kg every 48 hours 1
- For bacteremia/endocarditis: 6 mg/kg every 48 hours 1
- When possible, administer after hemodialysis on dialysis days 1
Critical caveat: Retrospective data suggests that discontinuation due to elevated CPK may be avoided by adjusting to every 48-hour dosing when CrCl <30 mL/min, with CPK elevation occurring at a median of 11.5 days 4. This suggests more frequent CPK monitoring than weekly is warranted in renally impaired patients 4.
Administration Details
Reconstitution and Preparation
- Reconstitute 500 mg vial with 10 mL of 0.9% sodium chloride to achieve 50 mg/mL concentration 1
- Avoid vigorous shaking to minimize foaming 1
- Allow wetted powder to stand 10 minutes undisturbed before gentle rotation 1
Infusion Methods for Adults
- 2-minute IV push: Administer reconstituted solution (50 mg/mL) directly 1
- 30-minute infusion: Dilute appropriate volume in 50 mL bag of 0.9% sodium chloride 1
Stability After Reconstitution
- Room temperature: 12 hours maximum 1
- Refrigerated (2-8°C): 48 hours maximum 1
- Combined storage time (vial + infusion bag) must not exceed these limits 1
Important Contraindications and Incompatibilities
Absolute Contraindication
- Do NOT use for pneumonia - daptomycin is inhibited by pulmonary surfactant and is contraindicated for aspiration pneumonia 2
- Exception: Effective for septic pulmonary emboli from bacteremia (different pathogenesis than aspiration pneumonia) 2
Drug Incompatibilities
- Never mix with dextrose-containing solutions - only use 0.9% sodium chloride 1
- Do not use with ReadyMED elastomeric pumps - causes leaching of 2-mercaptobenzothiazole impurity 1
Combination Therapy Recommendations
What NOT to Add
- Do not add gentamicin to daptomycin for bacteremia or native valve endocarditis 2
- Do not add rifampin to daptomycin for bacteremia or native valve endocarditis 2, 3
- These combinations do not improve outcomes and may prolong bacteremia duration 2
Safety Monitoring Requirements
CPK Monitoring
- Baseline CPK before initiating therapy 5
- Weekly CPK monitoring at minimum 5
- More frequent monitoring (potentially twice weekly) in renally impaired patients given median onset of 11.5 days 4
- Discontinue if CPK elevation occurs with muscle symptoms 4