Dosing and uses of Cubicin (daptomycin)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 500mg/vial
Skin Infections
4 mg/kg IV infusion q24hr for 7-14 days
Staphylococcus Aureus Bacteremia (Including Endocarditis)
6 mg/kg IV infusion q24hr for at least 2-6 weeks
Complicated Skin & Skin Structure Gram-Positive Bacterial Infections
6 mg/kg IV q24hr for 2-4 weeks
Spectrum of action
- Staphylococcus aureus (including MRSA)
- Streptococcus pyogenes
- Streptococcus agalactiae
- Streptococcus dysgalactiae ssp equisimilis
- Enterococcus faecalis (vancomycin-susceptible)
Dosage modifications
Renal impairment
- CrCl <30 mL/min: Give same dose q48hr
- On hemodialysis days, administer after hemodialysis
Dosing Considerations
Monitor creatine phosphokinase (CPK)
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Cubicin (daptomycin) adverse (side) effects
1-10%
Insomnia (9.0%)
Pharyngolaryngeal pain (8.0%)
Chest pain (7.0%)
Elevated blood creatine phosphokinase (7.0%)
Edema (7.0%)
Abdominal pain (6.0%)
Hypertension (6.0%)
Pruritus (6.0%)
Headache (5.4%)
Diarrhea (5.2%)
Sweating (5.0%)
Bacteremia (5.0%)
Sepsis (5.0%)
Rash (4.3%)
Abnormal LFTs (3.0%)
UTI (2.4%)
Hypotension (2.4%)
Dizziness (2.2%)
Dyspnea (2.1%)
Postmarketing Reports
Immune system disorders: Anaphylaxis; hypersensitivity reactions, including angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia; consider treatment with systemic steroids
Infections and infestations: Clostridium difficile–associated diarrhea
Musculoskeletal disorders: myoglobin increased; rhabdomyolysis;
Respiratory, thoracic, and mediastinal disorders: Cough, eosinophilic pneumonia
Nervous system disorders: Peripheral neuropathy
Skin and subcutaneous tissue disorders: Serious skin reactions, including Stevens-Johnson syndrome and vesiculobullous rash
Gastrointestinal disorders: Nausea, vomiting
Special senses: Visual disturbances
Blood and lymphatic system disorders: Anemia
General and administration site conditions: Pyrexia
Renal and urinary disorders: Acute kidney injury, renal insufficiency, and renal failure
Skin and Subcutaneous Tissue Disorders: Acute generalized exanthematous pustulosis
Warnings
Contraindications
Hypersensitivity
Cautions
Pseudomembranous colitis has been reported; may range from mild to life-threatening
Use cautiously in patients with peripheral neuropathies and myopathy; consider discontinuation
Discontinue with symptoms of myopathy and CPK >1000 U/L (>5x ULN), or no symptoms and CPK >2000 U/L (>10x ULN)
CPK elevations more prevalent if dosed more frequently than q24hr
Consider suspending statins during daptomycin therapy; theoretical risk of additive myopathy
Monitor INR closely for several days if on warfarin
May cause eosinophilic pneumonia characterized by fever, cough, shortness of breath, and difficulty breathing; may result in progressive respiratory failure and is potentially fataL
Prolonged use may result in fungal or bacterial superinfection
Perform susceptibility testing and rule out sequestered foci of infection if persisting or relapsing S. aureus bacteremia/endocarditis occurs
Evaluate patients for Clostridium difficile if diarrhea occurs
Avoid use in pediatric patients <12 months; potential nervous system or muscular system effects
Decreased efficacy reported in patients with moderate baseline renal impairment
Pregnancy and lactation
Pregnancy category: B
Lactation: Present in human milk but is poorly bioavailable orally; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cubicin (daptomycin)
Mechanism of action
Cyclic lipopeptide: Binds to bacterial membranes and causes rapid depolarization of membrane potential; causes inhibition of protein, DNA, RNA synthesis, and bacterial cell death
Absorption
Peak plasma time
- 0.5-0.8 hr
Peak plasma concentration
- 4 mg/kg dose: 58 mcg/mL
- 6 mg/kg dose: 94 mcg/mL
AUC
- 4 mg/kg dose: 494 mcg•hr/mL
- 6 mg/kg dose: 632 mcg•hr/mL
Distribution
Protein bound: 92%
Vd: 0.1 L/kg
Elimination
Half-life: 8 hr
Dialyzable: 11-15% of dose removed by continuous ambulatory peritoneal dialysis/hemodialysis
Renal clearance: 3.7-4.8 mL/hr/kg
Total body clearance: 8-9 mL/hr/kg
Excretion: Urine (78%)
Administration
IV Incompatibilities
Solution: Dextrose-containing diluents
Do not admix with other drugs
IV Compatibilities
Solution: NS, Lr
IV Preparation
Reconstitute 500 mg vial with 10 mL NS; dilute further with NS for infusion using aseptic technique (no preservatives or bacteriostatic agents)
Reconstituted solution and diluted infusion solution stable for 12 hr at room temperature and 48 hr at 2-8°C, but do not exceed combined storage time of 12 hr at room temperature and 48 hr refrigerated
IV Administration
Administer intravenously in 0.9% sodium chloride either by injection over 2 min or infusion over 30 min
Do not use in conjunction with ReadyMED elastometric infusion pumps
On hemodialysis days, administer after hemodialysis
