Can every Monday, Wednesday, Friday post-dialysis daptomycin (Cubicin) infusion achieve appropriate tissue levels compared to daily Intravenous (IV) dosing in patients with Impaired renal function?

Daptomycin Dosing in Hemodialysis Patients: MWF Post-Dialysis vs. Daily Administration

Daptomycin administered post-dialysis on Monday, Wednesday, and Friday (MWF) can achieve appropriate tissue levels comparable to daily IV dosing in patients with impaired renal function, provided appropriate dosing adjustments are made. 1

Pharmacokinetic Considerations

• Daptomycin is primarily eliminated by the kidneys, with approximately 78% of the administered dose recovered from urine, making dosage adjustment necessary in patients with renal impairment 1
• In patients with severe renal impairment (CrCl <30 mL/min) and those on hemodialysis, the mean AUC is approximately 2-3 times higher than in patients with normal renal function 1
• The half-life of daptomycin is significantly prolonged in patients with severe renal impairment (27.83 hours) and those on hemodialysis (30.51 hours) compared to patients with normal renal function (9.39 hours) 1

Dosing Recommendations for Dialysis Patients

• For patients on hemodialysis, daptomycin should be administered after the completion of hemodialysis on dialysis days 1
• The FDA-approved dosing for hemodialysis patients is based on the indication:
  • For skin and soft tissue infections: 4 mg/kg once every 48 hours 2
  • For bacteremia and endocarditis: 6 mg/kg once every 48 hours 2
• Post-dialysis administration on MWF schedule aligns well with the pharmacokinetics of daptomycin in hemodialysis patients due to its prolonged half-life in this population 1

Evidence Supporting MWF Dosing

• The extended half-life of daptomycin in hemodialysis patients (approximately 30 hours) provides a pharmacokinetic rationale for less frequent dosing 1
• Approximately 23% of daptomycin is removed during a standard hemodialysis session, supporting the practice of post-dialysis administration 3
• The volume of distribution at steady-state of daptomycin is approximately 0.1 L/kg, which allows for adequate tissue penetration even with less frequent dosing 1

Monitoring and Safety Considerations

• Creatine phosphokinase (CPK) levels should be monitored weekly in all patients receiving daptomycin, as CPK elevation is a potential adverse effect 2, 4
• In patients with renal impairment, CPK monitoring may need to be more frequent than once weekly, as CPK elevations may occur earlier (median time to onset of 11.5 days) 4
• When administered post-dialysis on MWF, the risk of drug accumulation is minimized compared to daily dosing without adjustment 1, 4

Potential Pitfalls and Considerations

• Underdosing is a concern in critically ill patients with severe infections; some studies suggest that daily dosing may be necessary in specific situations such as extended dialysis 3, 5
• For complex infections like endocarditis or osteomyelitis, higher doses (>6 mg/kg) have been explored and may be considered on a case-by-case basis 6
• Loss of daptomycin susceptibility has been reported in some patients with complex endovascular infections who were on hemodialysis, suggesting the need for careful monitoring of clinical response 4

Conclusion for Clinical Practice

• MWF post-dialysis administration of daptomycin is an appropriate dosing strategy for hemodialysis patients that can achieve tissue levels comparable to appropriately adjusted daily dosing 1
• This dosing schedule aligns with typical outpatient hemodialysis schedules, potentially improving medication adherence and reducing healthcare costs 4
• For severe or complex infections, higher doses may be considered while maintaining the post-dialysis administration schedule 6