From the Guidelines
Daptomycin is primarily cleared by the kidneys, with a high percentage of the administered dose being renally excreted. The mechanism of action of daptomycin involves disrupting cell membrane function via calcium-dependent binding, resulting in bactericidal activity in a concentration-dependent fashion 1. Key characteristics of daptomycin include:
- High protein binding of 91%
- Renal excretion as the primary route of clearance
- FDA approval for specific indications such as S. aureus bacteremia, right-sided infective endocarditis, and complicated skin and soft tissue infections (cSSTI) The fact that daptomycin is highly protein bound and renally excreted has significant implications for its use in patients with renal impairment 1. For patients with normal renal function, standard dosing is typically 4-6 mg/kg once daily, depending on the indication. However, for patients with impaired renal function, dose adjustments are necessary to prevent accumulation and potential toxicity. The predominantly renal elimination pathway of daptomycin means that its pharmacokinetics are significantly altered in patients with kidney disease, necessitating careful monitoring and dose adjustments in these populations.
From the FDA Drug Label
Daptomycin is eliminated primarily by the kidneys; therefore, a modification of daptomycin for injection dosage interval is recommended for adult patients with CL CR <30 mL/min, including patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) The route of clearance for daptomycin is renal clearance, with the drug being eliminated primarily by the kidneys 2.
- The drug can also be removed by hemodialysis and peritoneal dialysis, although this occurs slowly 2 2.
- Hemodialysis can remove approximately 15% of the administered dose over 4 hours, while peritoneal dialysis can remove approximately 11% of the administered dose over 48 hours 2.
From the Research
Route of Clearance for Daptomycin
- The primary route of clearance for daptomycin is renal, with approximately 50% of the dose excreted unchanged in the urine 3.
- This renal clearance is significant enough to require dosage adjustment in patients with renal insufficiency to prevent potential toxicity 3, 4, 5.
- The elimination half-life of daptomycin increases in patients with severe renal failure, indicating a decrease in renal clearance 5.
- Studies have shown that patients with creatinine clearance (CrCl) < 30 ml/min require adjusted dosing regimens, such as 4 mg/kg/48h for skin and soft tissue infections and 6 mg/kg/48h for bacteremia and right endocarditis, to achieve optimal efficacy and minimize toxicity 5, 6, 7.
- The pharmacokinetics of daptomycin are altered in patients with renal impairment, leading to increased exposure to unbound daptomycin and a higher probability of reaching efficacy targets, but also a higher risk of toxicity 6.