Daptomycin

Indications

Daptomycin is used for: Complicated skin and skin structure infections, Staphylococcus aureus bacteraemia

Adult Dose

Intravenous Complicated skin and skin structure infections Adult: 4 mg/kg once daily for 7-14 days, by infusion over 30 min or by inj over 2 min. Staphylococcus aureus bacteraemia Adult: 6 mg/kg once daily for 2-6 wk, by infusion over 30 min.

Child Dose

Staphylococcus Aureus Bacteremia Indicated for treatment of children aged 1-17 years with Staphylococcus aureus bacteremia <1 year: Safety and efficacy not established (see Dosing Considerations) >1 year 12-17 years: 7 mg/kg IV q24hr 7-11 years: 9 mg/kg IV q24hr 1-6 years: 12 mg/kg IV q24hr Duration of therapy: Up to 42 days Complicated Skin & Skin Structure Infections Indicated for the treatment of adult and pediatric patients (aged 1 to 17 yr) with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria <1 year: Safety and efficacy not established (see Dosing Considerations) >1 year 12-17 years: 5 mg/kg IV q24hr 7-11 years: 7 mg/kg IV q24hr 2-6 years: 9 mg/kg IV q24hr 1 to <2 years: 10 mg/kg IV q24hr Duration of therapy: Up to 14 days

Renal Dose

Renal impairment Complicated skin & skin structure infections (cSSSI) CrCl >30 mL/min: 4 mg/kg IV q24hr CrCl <30 mL/min: 4 mg/kg IV q48hr Hemodialysis and CAPD: 4 mg/kg IV q48hr administer following hemodialysis on hemodialysis days Staphylococcus aureus bacteremia CrCl >30 mL/min: 6 mg/kg IV q24hr CrCl <30 mL/min: 6 mg/kg IV q48hr Hemodialysis and CAPD: 6 mg/kg IV q48hr administer following hemodialysis on hemodialysis days

Administration

Reconstitute w/ 10 mL of NaCl 0.9% inj using aseptic technique. Gently rotate the vial to wet the powd and allow it to stand for 10 min. To obtain a completely reconstituted soln, gently swirl or rotate the vial. Do not shake/agitate vial during and after reconstitution. Further dilute the reconstituted soln w/ NaCl 0.9% inj for IV infusion. The final concentration should not exceed 20 mg/mL. IV Administration Adults On hemodialysis days, administer after hemodialysis IV push: Administer reconstituted solution IV over 2 min (in adults only) IV infusion: Infuse diluted solution IV over 30 min Pediatrics 1-6 years: Infuse diluted IV solution at rate of 0.42 mL/min over a 60-min period 7-17 years: Infuse diluted IV solution at rate of 1.67 mL/min over a 30-min period Do not administer Cubicin RF by injection over a two (2) minute period to 1-17 years

Contra Indications

Hypersensitivity

Precautions

Renal impairment. Patient w/ persisting or relapsing Staphylococcus aureus infection. Pregnancy and lactation. Closely monitor for signs and symptoms of eosinophilic pneumonia (e.g. new onset or worsening fever, dyspnoea). Serum creatine kinase should be monitored at least wkly during therapy.

Pregnancy-Lactation

Pregnancy Limited published data on use in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage; no evidence of adverse developmental outcomes observed in animal reproduction studies Lactation Limited published data report that daptomycin is present in human milk at infant doses of 0.1% of maternal dose; there is no information on effects of daptomycin on breastfed infant or effects of daptomycin on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

Interactions

Enhanced adverse/toxic effects w/ HMG-CoA reductase inhibitors (e.g. simvastatin). NSAIDs (e.g. diclofenac, ibuprofen) may reduce excretion of daptomycin and increase risk of renal impairment. Synergistic antibacterial effects against staphylococci and enterococci w/ aminoglycosides (e.g. gentamicin, tobramycin), rifampicin or β-lactam anti-infectives (e.g. penicillins, cephalosporins).

Adverse Effects

Side effects of Daptomycin : 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%)

Mechanism of Action

Daptomycin is a cyclic lipopeptide antibacterial derived from the fermentation of Streptomyces roseosporus. It causes bacterial cell death by binding to bacterial membranes and disrupting the membrane potential; thus inhibiting the synthesis of protein, DNA and RNA. Daptomycin exhibits rapid concentration-dependent bactericidal effects against susceptible gm+ve bacteria in vitro.