Usual Adult Dose for Skin and Structure Infection

10 mg/kg by IV infusion over 60 minutes every 24 hours for 7 to 14 days

Comments:

• Therapy duration should be guided by the severity and site of the infection and the patient's clinical progress.

Use: Treatment of complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, S. constellatus), or Enterococcus faecalis (vancomycin-susceptible isolates only).

Usual Adult Dose for Nosocomial Pneumonia

10 mg/kg by IV infusion over 60 minutes every 24 hours for 7 to 21 days

Comments:

• Therapy duration should be guided by the severity of the infection and the patient's clinical progress.
• This drug should be reserved for use when alternative treatments are not suitable.

Use: Treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Staphylococcus aureus (including methicillin-susceptible and -resistant isolates).

Renal Dose Adjustments

• CrCl 30 to 50 mL/min: 7.5 mg/kg by IV infusion every 24 hours
• CrCl 10 to less than 30 mL/min: 10 mg/kg by IV infusion every 48 hours
• CrCl less than 10 mL/min: Insufficient data available to make specific adjustment recommendation (per manufacturer product information).

Comments: Calculate CrCl using the Cockcroft-Gault formula and ideal body weight (IBW); use actual body weight if less than IBW.

Liver Dose Adjustments

• Mild and Moderate Liver Impairment: No adjustment recommended.
• Severe Liver Impairment: Data not available.

Precautions

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. It includes a medication guide and communication plan. For additional information: www.fda.gov/REMS.

US BOXED WARNING:

• INCREASED MORTALITY: Patients with pre-existing moderate/severe renal impairment (CrCl 50 mL/min or less) who were treated with this drug for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia had increased mortality versus vancomycin. Use of this drug in these patients should be considered only when the anticipated benefit outweighs the potential risk.
• NEPHROTOXICITY: New onset or worsening renal impairment has occurred; monitor renal function in all patients.
• FETAL RISK: Women of childbearing potential should have a serum pregnancy test prior to treatment. Avoid use of this drug during pregnancy unless the anticipated benefits to the patient outweigh the potential risk to the fetus. Adverse developmental outcomes observed in 3 animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

• Hemodialysis: Insufficient data available to make specific dosage adjustment recommendation (per manufacturer product information).

• Peritoneal dialysis: Data not available.

Other Comments

STORAGE REQUIREMENTS:

• Original packages should be refrigerated (2C to 8C/36F to 46F); excursions to ambient temperatures (up to 25C/77F) acceptable; excessive heat should be avoided.
• Total time of reconstituted solution in vial plus diluted (dosing) solution in infusion bag should not exceed 12 hours at room temperature and 7 days under refrigeration (2C to 8C/36F to 46F).
• Diluted (dosing) solution in infusion bag can also be stored at -30C to -10C/-22F to 14F for up to 32 days.

RECONSTITUTION/PREPARATION/SUSCEPTIBILITY TEST METHOD TECHNIQUES:
The manufacturer product information should be consulted.

IV COMPATIBILITY:

• Compatible IV infusion solutions: 5% Dextrose Injection, USP; 0.9% Sodium Chloride Injection, USP; Lactated Ringer's Injection, USP.
• Additives or other medications should not be added to vials of this drug or infused simultaneously through the same IV line.
• If the same IV line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of this drug with compatible IV infusion solutions.

GENERAL:
Spectrum of Activity:

• This drug exerts concentration-dependent bactericidal activity against susceptible Gram-positive organisms. In vitro studies demonstrated a post-antibiotic effect ranging from 1 to 6 hours against Staphylococcus aureus and other Gram-positive pathogens.
• In vitro and in clinical infections: This drug is active against most isolates of Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Enterococcus faecalis (vancomycin-susceptible isolates only), S. agalactiae, and S. anginosus group (including S. anginosus, S. intermedius, and S. constellatus).
• In vitro: This drug is active against E. faecium (vancomycin-susceptible isolates only), S. haemolyticus, S. dysgalactiae subspecies equisimilis, and S. epidermidis. Safety and efficacy in treating clinical infections due to these microorganisms have not been established.

Minimum Inhibitory Concentration (MIC)90:

• For S. aureus: 0.5 mcg/mL

Cross-Resistance:

• Some vancomycin-resistant enterococci have a reduced susceptibility to this drug. There is no known cross-resistance between this drug and other classes of antibacterial drugs.

Overdosage:

• A higher incidence of adverse reactions was observed in healthy study volunteers who received a dose of 15 mg/kg. Institute maintenance of glomerular filtration and careful monitoring of renal function in conjunction with supportive care. The use of hemodialysis and continuous venovenous hemofiltration to treat an overdose are unknown.

MONITORING:

• Cardiovascular: QTc interval
• Embryofetal Toxicity: Serum pregnancy test (before therapy in women of childbearing potential)
• Gastrointestinal: Diarrhea
• Hypersensitivity: Signs of hypersensitivity/allergic reaction (e.g., skin rash, anaphylaxis)
• Other: "Red-man Syndrome"-like reactions including upper body flushing, urticaria, pruritus, and rash; Ototoxicity (impaired hearing and inner ear disorders)
• Renal: Serum creatinine and CrCl (before therapy, at least every 48 to 72 hours during treatment, end of therapy)

PATIENT ADVICE:

• Take the full course of this drug treatment exactly as directed. Do not skip doses, even if you feel well.
• This drug only treats bacterial infections, not viral infections.
• Tell your healthcare provider about all the medicines you take, including over-the-counter drugs, vitamins, and herbal supplements.
• This drug may cause dizziness, drowsiness, confusion, and blurred vision; avoid driving and other activities such as operating machinery until you know how this drug affects you.