| Indications1 |
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Zyvox® formulations are indicated in the treatment of infections caused by susceptible strains of designated microorganisms and in patients with:
- Nosocomial pneumonia caused by methicillin-susceptible and -resistant Staphyloccus aureus (MSSA and MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP)
- Community-acquired pneumonia (CAP) caused by S. pneumoniae (including multidrug-resistant strains, MDRSP*), and cases with concurrent bacteremia, or methicillin-susceptible S. aureus strains
- Complicated skin and skin structure infections caused by MRSA and MSSA, Streptococcus pyogenes, or Streptococcus agalactiae
- Uncomplicated skin and skin structure infections caused by methicillin-susceptible S. aureus or S. pyogenes
- Vancomycin-resistant Enterococcus faecium infections
*MDRSP refers to isolates resistant to two or more of the following antibiotics: penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/sulfamethoxazole.
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| Clinical Evidence |
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- Proven linezolid efficacy in patients with nosocomial pneumonia due to MRSA2
- In the nosocomial pneumonia MRSA subset, Kaplan-Meier survival rates for linezolid versus vancomycin were 80.0% and 63.5%, respectively (p=0.03)2
- Clinical cure rates for linezolid versus vancomycin (excluding indeterminate or missing outcomes) were 59.0% and 35.5%, respectively (p<0.01)2
- Demonstrated clinical cure rates were comparable to those observed with vancomycin in the intent-to-treat (ITT) and S. aureus nosocomial pneumonia populations in a retrospective analysis of the 2 prospective clinical trials, previously summarized2-4(Fig 1)
A retrospective analysis of the 2 randomized, double-blind, comparator-controlled trials, previously summarized; the analysis compared the safety and efficacy of ZYVOX IV and vancomycin IV in 1019 (ITT population) patients with nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP). Patients were treated for 7 to 21 days with optional aztreonam 1 g to 2 g q8h. Clinical cure rates were assessed 12 to 28 days after end of therapy. Clinical cure was defined as the resolution of baseline signs and symptoms of pneumonia. Data from patients with indeterminate or missing clinical cure outcomes were excluded. Figure adapted from Wunderink et al. Chest. 20032
- Proven linezolid efficacy in patients with MRSA ventilator-associated pneumonia (VAP)5
- In the MRSA VAP subset, Kaplan-Meier survival rates for linezolid versus vancomycin therapy were 84.1% and 61.7%, respectively (p=0.02)5
- Clinical cure rates for linezolid versus vancomycin therapy were 62.2% and 21.2%, respectively (p=0.001)5
- Demonstrated clinical cure rates were comparable to those observed with vancomycin in the ITT VAP and S. aureus VAP populations in another retrospective analysis5 (Figure 2)
A retrospective analysis of the 2 randomized, double-blind, comparator-controlled trials, previously summarized compared the safety and efficacy of ZYVOX IV and vancomycin IV in 1019 (ITT population) patients with nosocomial pneumonia, including 544 patients with VAP. Patients were treated for 7 to 21 days with optional aztreonam 1 g to 2 g q8h. Clinical cure rates were assessed 12 to 28 days after end of therapy. Clinical cure was defined as the resolution of baseline signs and symptoms of pneumonia. Data from 110 patients with indeterminate or missing clinical cure outcomes were excluded (ZYVOX arm, 55 patients; vancomycin arm, 55 patients). Figure adapted from Kollef et al. Intensive Care Med. 2004.5
- Excellent epithelial lining fluid penetration6,7
- Pulmonary epithelial lining fluid concentrations of linezolid in healthy volunteers* remained above MIC90 values for S. aureus and S. pneumoniae throughout the 12-hour dosing interval6
- Linezolid concentration in epithelial lining fluid was 2 to 4 times greater than that found in plasma throughout the dosing interval6
* A prospective, open-label study of 25 healthy adult male volunteers; MIC90, minimum inhibitory concentration required to inhibit 90% of organisms; pharmacokinetic data do not necessarily correlate with clinical results
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| Safety Profile1 |
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ADVERSE REACTIONS: Diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, dizziness, fever.
INTERACTIONS: Adrenergic and serotonergic agents; strong cytochrome P450 enzyme inducers.
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| Dosages1 |
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| Infection* |
Dosage and route of administration |
Recommended treatment duration (consecutive days) |
| Children (Birth - 11 years old) |
Adults and adolescents(≥12 years old) |
| Complicated skin and skin structure infections |
10 mg/kg IV or oral q8h |
600 mg IV or oral q12h |
10 to 14 |
| Community-acquired pneumonia, including concurrent bacteremia |
| Nosocomial pneumonia |
| Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia |
10 mg/kg IV or oral q8h |
600 mg IV or oral q12h |
14 to 28 |
| Uncomplicated skin and skin structure infections |
<5 yrs: 10 mg/kg oral q8h
5-11 yrs: 10 mg/kg oral q12h |
Adults: 400 mg oral q12h
Adolescents: 600 mg oral q12h |
10 to 14 |
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* Due to designated pathogens
| Strengths1 |
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Film-coated tablet: 400 mg, 600 mg
Oral suspension: 100 mg/5 mL
Intravenous injection: 2 mg/mL
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| Packing1 |
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Film-coated tablets: 400 mg x 100’s; 400 mg x 20’s; 600 mg x 100’s; 600 mg x 20’s
Oral suspension: 100 mg/5 mL in 240-mL glass bottle
Intravenous injection: (per bag) 200 mg/100 mL; 400 mg/200 mL; 600 mg/300 mL
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| Important Safety Information1 |
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CONTRAINDICATIONS: Known hypersensitivity to linezolid or any of the excipients. Concomitant use of linezolid and monoamine oxidase inhibitors or serotonergic agents may potentiate the risk of elevated BP and serotonin syndrome.
PRECAUTIONS: Myelosuppression (incl. anemia, leucopenia, pancytopenia, and thrombocytopenia); Mortality imbalance in an investigational study in patients with catheter-related bloodstreem infections, ie, catheter-site infections; Clostridium difficile-associated diarrhea (CDAD); lactic acidosis; serotonin syndrome; peripheral and optic neuropathy; convulsions. (Please refer to the full Prescribing Information for details).
ADVERSE REACTIONS: Diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, dizziness, fever.
POST-MARKETING ADVERSE REACTIONS: Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia); peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision; lactic acidosis; serotonin syndrome; convulsions; superficial tooth and tongue discoloration; anaphylaxis, angioedema, and bullous skin disorders such as those described in Stevens Johnson; because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made and causal relationship cannot be precisely established.
PREGNANCY and LACTATION: Pregnancy category C – should only be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when administered to a nursing woman as it is not known whether linezolid is excreted in human milk.
Please refer to full prescribing information for more safety information.
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Please review the full product information or package insert before prescribing. |
| References |
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1. Zyvox® (linezolid) Prescribing Information. Pfizer Corporation Hong Kong Limited: 28 July 2010.
2. Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Linezolid vs vancomycin: Analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003;124(5):1789-1797.
3. Rubinstein E, Cammarata SK, Oliphant TH, Wunderink RG. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: A randomized, double-blind, multicenter study. Clin Infect Dis. 2001;32(3):402-412.
4. Wunderink RG, Cammarata SK, Oliphant TH, Kollef MH. Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia. Clin Ther. 2003;25(3):980-992.
5. Kollef M, Rello J, Cammarata S, Croos-Dabrera R, Wunderink R. Clinical cure and survival in Gram-positive ventilator-associated pneumonia: Retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med. 2004;30(3):388-394.
6. Conte JE, Jr., Golden JA, Kipps J, Zurlinden E. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother. 2002;46(5):1475-1480.
7. Boselli E, Breilh D, Rimmelé T, et al. Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia. Crit Care Med. 2005;33(7):1529-1533.
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Please review the full product information or package insert before prescribing.
ZYX11005P |
