INDICATIONS AND USAGE
ZYVOX formulations are indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms (see PRECAUTIONS, Pediatric Use and DOSAGE AND ADMINISTRATION and CLINICAL STUDIES). Linezolid is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected (see WARNINGS).
Vancomycin-Resistant Enterococcus faecium infections, including cases with concurrent bacteremia.
Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), or Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]).
Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. ZYVOX has not been studied in the treatment of decubitus ulcers.
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible only) or Streptococcus pyogenes.
Community-acquired pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]), including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
DOSAGE AND ADMINISTRATION
The recommended dosage for ZYVOX formulations for the treatment of infections is described in Table 14.
Table 14. Dosage Guidelines for ZYVOX
InfectionDue to the designated pathogens (see INDICATIONS AND USAGE)
|Dosage and Route of Administration||Recommended Duration of Treatment (consecutive days)|
|Pediatric Patients Neonates <7 days: Most pre-term neonates < 7 days of age (gestational age < 34 weeks) have lower systemic linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg q12h. Consideration may be given to the use of 10 mg/kg q8h regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg q8h by 7 days of life (see CLINICAL PHARMACOLOGY, Special Populations, Pediatric). (Birth through 11 Years of Age)||Adults and Adolescents (12 Years and Older)|
|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|
|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|
Adult patients with infection due to MRSA should be treated with ZYVOX 600 mg q12h.
In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with MICs of 4 µg/mL treated with ZYVOX had clinical cures. However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure (AUC) compared with adults. In pediatric patients with a sub-optimal clinical response, particularly those with pathogens with MIC of 4 µg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response (see CLINICAL PHARMACOLOGY, Special Populations, Pediatric and PRECAUTIONS, Pediatric Use).
In controlled clinical trials, the protocol-defined duration of treatment for all infections ranged from 7 to 28 days. Total treatment duration was determined by the treating physician based on site and severity of the infection, and on the patient's clinical response.
No dose adjustment is necessary when switching from intravenous to oral administration. Patients whose therapy is started with ZYVOX I.V. Injection may be switched to either ZYVOX Tablets or Oral Suspension at the discretion of the physician, when clinically indicated.
ZYVOX I.V. Injection is supplied in single-use, ready-to-use infusion bags (see HOW SUPPLIED for container sizes). Parenteral drug products should be inspected visually for particulate matter prior to administration. Check for minute leaks by firmly squeezing the bag. If leaks are detected, discard the solution, as sterility may be impaired.
ZYVOX I.V. Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. Do not use this intravenous infusion bag in series connections. Additives should not be introduced into this solution. If ZYVOX I.V. Injection is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each product. In particular, physical incompatibilities resulted when ZYVOX I.V. Injection was combined with the following drugs during simulated Y-site administration: amphotericin B, chlorpromazine HCl, diazepam, pentamidine isothionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole. Additionally, chemical incompatibility resulted when ZYVOX I.V. Injection was combined with ceftriaxone sodium.
If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of ZYVOX I.V. Injection with an infusion solution compatible with ZYVOX I.V. Injection and with any other drug(s) administered via this common line (see Compatible Intravenous Solutions).
Compatible Intravenous Solutions
- 5% Dextrose Injection, USP
- 0.9% Sodium Chloride Injection, USP
- Lactated Ringer's Injection, USP
Keep the infusion bags in the overwrap until ready to use. Store at room temperature. Protect from freezing. ZYVOX I.V. Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.
Constitution of Oral Suspension
ZYVOX for Oral Suspension is supplied as a powder/granule for constitution. Gently tap bottle to loosen powder. Add a total of 123 mL distilled water in two portions. After adding the first half, shake vigorously to wet all of the powder. Then add the second half of the water and shake vigorously to obtain a uniform suspension. After constitution, each 5 mL of the suspension contains 100 mg of linezolid. Before using, gently mix by inverting the bottle 3 to 5 times. DO NOT SHAKE. Store constituted suspension at room temperature. Use within 21 days after constitution.
ZYVOX I.V. Injection is available in single-use, ready-to-use flexible plastic infusion bags in a foil laminate overwrap. The infusion bags and ports are latex-free. The infusion bags are available in the following package sizes:
|100 mL bag (200 mg linezolid)||NDC 0009-5137-01|
|200 mL bag (400 mg linezolid)||NDC 0009-5139-01|
|300 mL bag (600 mg linezolid)||NDC 0009-5140-01|
ZYVOX Tablets are available as follows:
400 mg (white, oblong, film-coated tablets printed with "ZYVOX 400mg")
|100 tablets in HDPE bottle||NDC 0009-5134-01|
|20 tablets in HDPE bottle||NDC 0009-5134-02|
|Unit dose packages of 30 tablets||NDC 0009-5134-03|
600 mg (white, capsule-shaped, film-coated tablets printed with "ZYVOX 600 mg")
|100 tablets in HDPE bottle||NDC 0009-5135-01|
|20 tablets in HDPE bottle||NDC 0009-5135-02|
|Unit dose packages of 30 tablets||NDC 0009-5135-03|
ZYVOX for Oral Suspension is available as a dry, white to off-white, orange-flavored granule/powder. When constituted as directed, each bottle will contain 150 mL of a suspension providing the equivalent of 100 mg of linezolid per each 5 mL. ZYVOX for Oral Suspension is supplied as follows:
|100 mg/5 mL in 240-mL glass bottles||NDC 0009-5136-01|
Storage of ZYVOX Formulations
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light. Keep bottles tightly closed to protect from moisture. It is recommended that the infusion bags be kept in the overwrap until ready to use. Protect infusion bags from freezing.