University of Nebraska Medical Center

Daptomycin (Cubicin)

The Pharmacy and Therapeutics Committee voted to add daptomycin to the inpatient formulary with Antimicrobial Restrictions, effective March 21st, 2005. The Antimicrobial Restrictions are in place due to concerns regarding a variety of issues: off-label use; the need for increased dosage for patients with bacteremia/endocarditis or other serious infections due to gram-positive pathogens; contraindication for daptomycin use in patients with pneumonia.

In order to make this medication available as a formulary agent for the general medical staff, to ensure appropriate usage, and to protect the medical staff from medical/legal considerations, the Pharmacy and Therapeutics Committee has approved the following requirements for daptomycin use:

  1. Use of this drug, without Antimicrobial Restrictions, is allowed for FDA-labeled indications only (see below).
  2. A written indication for use must accompany ALL daptomycin orders in the permanent medical record. Empiric orders should include site of infection and possible infecting organism(s).
    1. Any off-label use will require review and approval for continued use by the Infectious Disease (ID) Service. The ordering physician is responsible for contacting the ID service. A single dose only of daptomycin (6 mg/kg for bacteremia, endocarditis, or osteomyelitis) will be dispensed pending ID response; therefore, the review must be initiated within 24 hours of the original order.
    2. If off-label use is approved, the ID Service will relay this information to the ordering physician as well as to the pharmacy for continued administration of daptomycin. If daptomycin is thought to be inappropriate, the ID Service will provide alternative recommendations and communicate these recommendations to the physician originating the daptomycin order.

If you have any questions regarding this policy, please direct them to the Antimicrobial Stewardship Program (ASP) by contacting Scott Bergman, PharmD via email at scbergman@nebraskamed.com or telephone at 402.559.4149.

Daptomycin Review

Daptomycin is the first member of a new class of antibiotics called cyclic lipopeptides. Lipopeptides exhibit calcium dependent binding to bacterial plasma cell membranes. Once bound to the cell membranes, daptomycin causes potassium ions to leak from the cell, which causes a depolarization of membrane potential and eventual cell death. Daptomycin is a concentration-dependent, bactericidal agent with activity against gram-positive organisms.

The FDA-approved indications for daptomycin are for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only); and for the treatment of bacteremia and right-sided endocarditis caused by Staphylococcus aureus (including methicillin-resistant isolates). The recommended dosing of daptomycin for cSSSIs is 4 mg/kg once daily for 7 to 14 days; the recommended dose of daptomycin for bacteremia and/or endocarditis is 6 mg/kg once daily for 2 to 6 weeks. The dosing interval should be extended to 48 hours in patients with severe renal insufficiency (CrCl < 30 mL/min, including hemodialysis or peritoneal dialysis). Daptomycin is NOT indicated for the treatment of pneumonia. Phase III trials of community acquired pneumonia (CAP) treated with daptomycin resulted in a higher incidence of death and serious cardiorespiratory adverse events versus CAP treated with comparator agents.

Daptomycin can cause skeletal muscle myopathy with elevations in CPK. The percentage of patients treated with daptomycin in phase III trials who experienced muscle pain or weakness associated with CPK elevations > 4x ULN was 0.2%. Myopathy is fully reversible when therapy is withdrawn. Co-administration of daptomycin and HMG-CoA reductase inhibitors ("statins") may result in a possible increased risk of myopathy. The temporary suspension of HMG-CoA reductase inhibitors while receiving daptomycin is recommended. Patient's receiving daptomycin therapy should have CPK levels drawn weekly. Daptomycin should be discontinued in patients with symptoms of muscle pain or weakness whose CPK levels exceed 1000 U/L (~ 5x ULN), or in patients without symptoms whose CPK exceeds 10x ULN.

Daptomycin vs Vancomycin
Drug Cost Cost/14 days
70 kg pt
Monitoring Costs 14 days Total Cost
70 kg pt
Daptomycin $152 per 500mg vial $1,191.68* $7.52 (X2 CPK level) $1,199.20
Vancomycin $43.34 per 10gram vial $121.35
(1g q12h)
$80.00 (X5 peak/trough levels) $201.35
*does not include cost of wasted drug- waste cost is $66.88 per day or $936.32 for 14 days for a 70kg patient