Daptomycin Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Skin and Structure Infection

Complicated: 4 mg/kg IV every 24 hours for 7 to 14 days

Usual Adult Dose for Endocarditis

Staphylococcus aureus bloodstream infections, including those with right-sided infective endocarditis: 6 mg/kg IV every 24 hours for 2 to 6 weeks

Usual Adult Dose for Bacteremia

Staphylococcus aureus bloodstream infections: 6 mg/kg IV every 24 hours for 2 to 6 weeks

Renal Dose Adjustments

CrCl less than 30 mL/min:
Complicated skin and skin structure infections: 4 mg/kg IV every 48 hours
Staphylococcus aureus bloodstream infections: 6 mg/kg IV every 48 hours

Liver Dose Adjustments

Mild to moderate hepatic impairment: No adjustment recommended.
Severe hepatic impairment: Data not available

Precautions

Anaphylaxis/hypersensitivity reactions have been reported with daptomycin and may be life-threatening. Daptomycin should be discontinued and appropriate therapy should be instituted if an allergic reaction to the drug occurs.

Patients should be monitored for the development of muscle pain or weakness, especially of distal extremities, and creatine phosphokinase (CPK) levels should be monitored weekly. Levels should be monitored more often in patients with recent prior or concurrent treatment with HMG-CoA reductase inhibitors or if CPK elevations occur during treatment. Renal function and CPK should be monitored more often than once weekly in patients with renal impairment. Daptomycin should not be dosed more often than once a day as CPK elevations seemed to occur more frequently during clinical trials at such a frequency. Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy along with CPK elevations greater than 1000 units/L (about 5 times ULN), and in patients without symptoms who have CPK elevations 10 times ULN or greater. The temporary discontinuation of drugs associated with rhabdomyolysis (such as HMG-CoA reductase inhibitors) should be considered during daptomycin therapy.

Eosinophilic pneumonia has been reported in patients receiving daptomycin. Eosinophilic pneumonia may lead to progressive respiratory failure and is potentially fatal if not quickly recognized and appropriately managed. Diffuse pulmonary infiltrates, fever, and dyspnea with hypoxic respiratory insufficiency have been reported in cases associated with daptomycin. In general, eosinophilic pneumonia developed 2 to 4 weeks after the start of therapy and improved when daptomycin was discontinued and steroid therapy was started. Recurrence of eosinophilic pneumonia has been reported upon reexposure. Patients should be closely monitored for signs and symptoms of eosinophilic pneumonia (including new onset or worsening fever, dyspnea, cough, and new infiltrates on chest imaging studies). Patients who develop these signs and symptoms should undergo prompt medical evaluation and should discontinue daptomycin at once. Treatment with systemic steroids is recommended.

Peripheral neuropathy has been reported during postmarketing experience. Clinicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving daptomycin.

Clostridium difficile associated diarrhea (CDAD) has been reported with almost all antibiotics and may potentially be life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea following daptomycin therapy. Mild cases generally improve with discontinuation of the drug, while severe cases may require supportive therapy and treatment with an antimicrobial agent effective against C difficile. Hypertoxin producing strains of C difficile cause increased morbidity and mortality; these infections can be resistant to antimicrobial treatment and may necessitate colectomy.

The impurity 2-mercaptobenzothiazole (MBT) has been isolated from reconstituted daptomycin stored in ReadyMED (R) elastomeric infusion pumps. The clinical significance of this finding is unknown. Daptomycin should not be used in conjunction with ReadyMED (R) elastomeric infusion pumps.

Superinfection with nonsusceptible organisms (i.e., yeasts) may occur with antibiotic therapy. Appropriate measure should be taken if superinfection occurs during treatment.

Lower clinical success rates and higher rates of adverse effects have been observed with daptomycin in elderly patients (65 years or older).

Limited data have shown decreased efficacy in patients with moderate baseline renal impairment (CrCl less than 50 mL/min). These data should be considered when selecting antibacterial therapy for patients with baseline moderate to severe renal impairment.

Repeat blood cultures are recommended for patients with persisting or relapsing Staphylococcus aureus bacteremia/endocarditis or poor clinical response. Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial regimen may be required.

Safety and efficacy have not been established in pediatric patients (less than 18 years of age).

Dialysis

CrCl less than 30 mL/min, including hemodialysis and CAPD:
Complicated skin and skin structure infections: 4 mg/kg IV every 48 hours
Staphylococcus aureus bloodstream infections: 6 mg/kg IV every 48 hours

Daptomycin should be administered after hemodialysis on hemodialysis days.

Other Comments

Daptomycin should be administered either via IV injection over 2 minutes or via IV infusion over 30 minutes.

Combination therapy may be clinically indicated if the documented or presumed pathogens include Gram-negative or anaerobic organisms. Daptomycin is not indicated for the treatment of left-sided infective endocarditis due to Staphylococcus aureus or for the treatment of pneumonia. Daptomycin has not been studied in patients with prosthetic valve endocarditis.

There are limited safety data for the use of daptomycin beyond 28 days.

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