Buy Linezolid (Zyvox) Without Prescription 600mg

Linezolid is a synthetic oxazolidinone anti-infective agent that is active against enterococci, staphylococci, and streptococci. Molecular Formula: C16H20FN3O4

Uses

Linezolid is used orally and/or IV for the treatment of vancomycin-resistant Enterococcus faecium infections and for the treatment of community-acquired pneumonia, nosocomial pneumonia, and uncomplicated or complicated skin and skin structure infections caused by susceptible staphylococci or streptococci. Concomitant use of another anti-infective may be indicated in the treatment of some of these infections (e.g., nosocomial pneumonia, complicated skin and skin structure infections) if the documented or presumptive pathogens also include gram-negative bacteria.

Vancomycin-resistant Enterococcus faecium Infections

Linezolid is used for the treatment of vancomycin-resistant E. faecium infections, including those associated with concurrent bacteremia. In a randomized, double-blind study in adults comparing high-dose linezolid (600 mg every 12 hours IV or orally) with low-dose linezolid (200 mg every 12 hours IV or orally) for 7-28 days, cure rates for patients with documented vancomycin-resistant E. faecium at any infection site were 67 or 52% for those receiving high- or low-dose linezolid, respectively, based on intent-to-treat analysis. Some patients received concomitant therapy with aztreonam or aminoglycosides. Compared with patients in the high-dose group, there were more adverse events and more deaths among patients in the low-dose group.

Efficacy of linezolid for the treatment of vancomycin-resistant E. faecium infections in pediatric patients is supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic studies in neonates and pediatric patients up to 17 years of age, and data from a randomized, open-label, comparator-controlled study of documented or suspected gram-positive bacterial infections in pediatric patients younger than 12 years of age.

Respiratory Tract Infections

Community-acquired Pneumonia

Linezolid is used for the treatment of community-acquired pneumonia (CAP) caused by susceptible strains of S. pneumoniae (established for penicillin-susceptible strains only), including those associated with concurrent bacteremia, or susceptible strains of Staphylococcus aureus (established for oxacillin-susceptible [previously known as methicillin-susceptible] strains only).

Because linezolid does not provide coverage against all pathogens that may be involved in CAP (e.g., Haemophilus influenzae), the drug is not usually considered a first- or second-line drug for empiric treatment of CAP. For information on empiric regimens recommended for treatment of CAP. In 2 randomized clinical studies in patients 13 years of age or older with CAP, cure rates with linezolid (600 mg every 12 hours for 7-14 days orally or IV followed by oral administration) were similar (approximately 90%) to those achieved with oral cefpodoxime proxetil (200 mg every 12 hours for 10-14 days) or IV ceftriaxone (1 g every 12 hours) followed by oral cefpodoxime proxetil (200 mg every 12 hours) for 7-14 days. Linezolid was substantially more effective than ceftriaxone followed by cefpodoxime in a subset of hospitalized patients with CAP and associated S. pneumoniae bacteremia (93.3 versus 69.6%, respectively).

Efficacy of linezolid for the treatment of CAP in pediatric patients is supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic studies in neonates and pediatric patients up to 17 years of age, an uncontrolled study in pediatric patients 8 months through 12 years of age, and data from a randomized, open-label, comparator-controlled study of documented or suspected gram-positive bacterial infections in pediatric patients younger than 12 years of age.

Nosocomial Pneumonia

Linezolid is used for the treatment of nosocomial pneumonia caused by susceptible strains of S. aureus (oxacillin-susceptible and -resistant strains) or S. pneumoniae (established for penicillin-susceptible strains only). Concomitant use of another anti-infective should be considered if the documented or presumptive pathogens include gram-negative organisms. In a randomized, double-blind study in adults with nosocomial pneumonia, cure was achieved in 57% of clinically evaluable patients receiving linezolid (600 mg every 12 hours IV for 7-21 days) compared with 60% of those receiving vancomycin (1 g every 12 hours IV for 7-21 days). Both treatment groups also received concomitant therapy with aztreonam (1-2 g every 8 hours IV) for gram-negative coverage.

Efficacy of linezolid for the treatment of nosocomial pneumonia in children is supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic studies in neonates and pediatric patients up to 17 years of age, and data from a randomized, open-label, comparator-controlled study of documented or suspected gram-positive bacterial infections in pediatric patients younger than 12 years of age. In the comparator-controlled study in pediatric patients with documented or suspected gram-positive infections, cure rates in those with nosocomial pneumonia were 72% in those receiving linezolid and 92% in those receiving vancomycin based on intent-to-treat analysis; however, cure rates in clinically evaluable children with nosocomial pneumonia receiving linezolid were similar to rates in clinically evaluable children receiving vancomycin.

Skin and Skin Structure Infections

Linezolid is used for the treatment of uncomplicated skin and skin structure infections caused by S. aureus (oxacillin-susceptible strains) or S. pyogenes (group A b-hemolytic streptococci) and for complicated skin and skin structure infections, including diabetic foot infections without concurrent osteomyelitis, caused by S. aureus (oxacillin-susceptible and -resistant strains), S. pyogenes, or S. agalactiae (group B streptococci).

The use of linezolid in the treatment of decubitus ulcers has not been studied. Concomitant use of another anti-infective may be appropriate if the documented or presumptive pathogens include gram-negative bacteria. In a randomized, double-blind clinical study in adults with complicated skin and skin structure infections, the efficacy rates (clinical, microbiologic, and overall outcomes) were similar for linezolid (600 mg every 12 hours IV initially, with an option to convert to oral administration) or oxacillin (2 g every 6 hours IV) with an option to switch to oral dicloxacillin (500 mg every 6 hours) for 10-21 days. Patients in both treatment groups received concomitant aztreonam (1-2 g every 6-8 hours IV) if empiric gram-negative coverage was considered necessary. In a randomized clinical study in patients 13 years of age or older with known or suspected oxacillin-resistant skin and skin structure infections, efficacy (clinical, microbiologic, and overall outcomes) was similar for therapy with linezolid (600 mg every 12 hours IV initially, with an option to convert to oral administration) or vancomycin (1 g every 12 hours IV) for 14-28 days. In adults with uncomplicated skin and skin structure infections, similar cure rates were achieved with either oral linezolid (400 mg twice daily) or clarithromycin (250 mg twice daily) for 7-14 days in 2 identically designed, randomized, double-blind clinical studies.

In a randomized, multicenter open-label comparative study in adults with diabetic foot infections, efficacy rates (clinical and microbiologic outcomes) were similar in patients receiving linezolid (600 mg every 12 hours IV or orally) or an aminopenicillin (ampicillin sodium and sulbactam sodium 1.5-3 g every 6 hours IV, amoxicillin and clavulanate potassium 500-875 mg every 8-12 hours orally, or amoxicillin and clavulanate potassium 0.5-2 g every 6 hours IV [IV preparation not commercially available in the US]) for 14-28 days. Patients in both treatment groups received concomitant aztreonam (1-2 g every 8-12 hours IV) if gram-negative pathogens were isolated from the infection site and patients receiving an aminopenicillin also were treated with vancomycin (1 g every 12 hours IV) if oxacillin-resistant S. aureus was isolated from the foot infection.

Efficacy of linezolid for the treatment of complicated skin and skin structure infections in pediatric patients is supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic studies in neonates and pediatric patients up to 17 years of age, and data from a randomized, comparator-controlled study of documented or suspected gram-positive bacterial infections in pediatric patients younger than 12 years of age. In the comparator-controlled study in pediatric patients with documented or suspected gram-positive infections, cure rates in children with complicated skin and skin structure infections were 85% in those receiving linezolid and 91% in those receiving vancomycin based on intent-to-treat analysis; however, cure rates in clinically evaluable children with complicated skin and skin structure infections receiving linezolid were similar to cure rates in clinically evaluable children receiving vancomycin.

Efficacy of linezolid for the treatment of uncomplicated skin and skin structure infections in pediatric patients caused by S. aureus (oxacillin-susceptible strains) or S. pyogenes is supported by data from a comparator-controlled study in pediatric patients 5-17 years of age.

Dosage and Administration

Reconstitution and Administration

Linezolid is administered orally or by IV infusion.

Oral Administration

Orally administered linezolid may be given without regard to meals. However, large quantities of foods or beverages with high tyramine content should be avoided while taking linezolid. Linezolid powder for oral suspension should be reconstituted at the time of dispensing with the amount of water specified on the bottle to provide a suspension containing 100 mg/5 mL. After tapping the bottle gently to loosen the powder, the water should be added in 2 portions, and the suspension agitated well after each addition. Prior to administration of each dose, the suspension should be gently mixed by inverting the bottle 3-5 times.

IV Administration

Linezolid premixed injection for IV administration in single-use flexible containers should be infused over 30-120 minutes without further dilution. Linezolid premixed solutions should be inspected visually for particulate matter prior to administration and should not be used if visible particles are evident. The solution may exhibit a yellow color that can intensify over time without adversely affecting potency.

The bags should be squeezed firmly to check for minute leaks. If leaks are detected, the solution should be discarded as sterility may be impaired. Linezolid premixed injection for IV administration in single-use flexible infusion bags should not be used in series connections, and additives should not be introduced into the solution. During simulated Y-site administration, linezolid was physically incompatible with amphotericin B, chlorpromazine hydrochloride, diazepam, erythromycin lactobionate, pentamidine isethionate, phenytoin sodium, and co-trimoxazole. In addition, linezolid is chemically incompatible with ceftriaxone sodium. Linezolid is compatible with 5% dextrose, 0.9% sodium chloride, and lactated Ringer’s injection.

General Dosage

The usual oral or IV dosage of linezolid for the treatment of vancomycin-resistant Enterococcus faecium infections or for the treatment of community-acquired pneumonia (CAP), nosocomial pneumonia, or complicated skin and skin structure infections caused by susceptible staphylococci or streptococci in adults and adolescents 12 years of age or older is 600 mg every 12 hours. For the treatment of uncomplicated skin and skin structure infections caused by susceptible staphylococci or streptococci, the usual oral dosage of linezolid is 400 mg every 12 hours in adults and 600 mg every 12 hours in adolescents.

Skin and skin structure infections in adults caused by oxacillin-resistant S. aureus (previously known as methicillin-resistant S. aureus) should be treated with linezolid 600 mg every 12 hours. The usual oral or IV dosage of linezolid for the treatment of vancomycin-resistant E. faecium infections or for the treatment of CAP, nosocomial pneumonia, or complicated skin and skin structure infections caused by susceptible staphylococci or streptococci in pediatric patients younger than 12 years of age is 10 mg/kg every 8 hours. For the treatment of uncomplicated skin and skin structure infections caused by susceptible staphylococci or streptococci in pediatric patients, the usual oral dosage of linezolid is 10 mg/kg every 8 hours in those younger than 5 years of age and 10 mg/kg every 12 hours in those 5-11 years of age. In premature neonates younger than 7 days of age, linezolid therapy should be initiated in a dosage of 10 mg/kg every 12 hours; a dosage of 10 mg/kg every 8 hours may be considered in neonates with an inadequate response to the lower dosage. By 7 days of age, all neonates should receive linezolid in a dosage of 10 mg/kg every 8 hours.

When clinically appropriate, patients treated initially with IV linezolid may be switched to oral linezolid without dosage adjustment. The recommended duration of linezolid therapy is 14-28 days in patients with vancomycin-resistant E. faecium infections (including those with concurrent bacteremia) and 10-14 days in those with CAP (including those with concurrent bacteremia), nosocomial pneumonia, or complicated or uncomplicated skin and skin structure infections caused by susceptible staphylococci or streptococci.

Special Populations

No special population dosage recommendations at this time. There are no clinical data on the use of linezolid in patients with severe renal or hepatic (Child Pugh class C) impairment. However, the 2 principal metabolites of linezolid may accumulate in patients with severe renal insufficiency; clinical importance has not been determined. Patients on hemodialysis should receive linezolid after the dialysis session. It is not known whether linezolid or its metabolites are removed by peritoneal dialysis.

Cautions

Contraindications

Known hypersensitivity to linezolid or any ingredient in the formulation.

Warnings/Precautions

Warnings Hematologic Effects

Myelosuppression (e.g., anemia, leukopenia, pancytopenia, thrombocytopenia) has been reported in patients receiving linezolid. Discontinuance of therapy should be considered. Hematologic parameters generally have returned toward pretreatment values following discontinuance of linezolid. Complete blood cell counts should be monitored weekly, especially in patients who require longer than 2 weeks of linezolid therapy, who have preexisting myelosuppression, who are receiving concomitant drugs that produce bone marrow suppression, or who have a chronic infection that was or is being treated with concomitant anti-infective therapy.

Major Toxicities Clostridium difficile-associated Colitis

Reported with numerous anti-infectives, including linezolid; may range in severity from mild to life-threatening. Evaluate and monitor patients who develop diarrhea during therapy.

General Precautions Lactic Acidosis

Lactic acidosis, characterized by recurrent nausea and vomiting, has been reported in patients receiving linezolid. Patients who develop recurrent nausea and vomiting, unexplained acidosis, or a low bicarbonate concentration while receiving linezolid should undergo immediate medical evaluation.

Monamine Oxidase Inhibition

Linezolid is a weak, nonselective, reversible inhibitor of monoamine oxidase (MAO). Patients should be instructed to consume less than 100 mg of tyramine per meal while they are taking linezolid. For additional information on food interactions in patients receiving MAO inhibitors, including examples of foods that may have a high tyramine content.

Resistance

Because of concerns about increased microbial resistance to anti-infective agents due to inappropriate use, the manufacturer states that clinicians should consider alternative anti-infectives to linezolid when prescribing an anti-infective for outpatient use. Some clinicians recommend that linezolid be reserved for treatment of well-documented, serious vancomycin-resistant enterococcal infections.

Phenylketonuria

Individuals who must restrict their intake of phenylalanine should be warned that Zyvox® for oral suspension contains aspartame, which is metabolized in the GI tract following oral administration, to provide 20 mg of phenylalanine per 5 mL of suspension. The other linezolid formulations do not contain aspartame.

Other Precautions

Linezolid has not been studied in patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism.

Specific Populations Pregnancy Category C.

Lactation Linezolid and its metabolites are distributed into milk in rats; caution if used in nursing women.

Pediatric Use

Safety and efficacy of linezolid in pediatric patients is supported by adequate and well-controlled studies in adults, pharmacokinetic studies in children from birth to 17 years of age, and data from uncontrolled and controlled studies in children. Safety of the drug has been evaluated in 248 pediatric patients 5-11 years of age with uncomplicated skin and skin structure infections and in 215 pediatric patients younger than 12 years of age with other infections who received linezolid for up to 28 days. In these studies, 83-99% of adverse effects were described as mild or moderate. While some pharmacokinetic parameters (i.e., peak plasma concentration, volume of distribution) are similar in children of all ages, linezolid clearance varies with age. Excluding neonates younger than 1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as children age, the clearance of linezolid decreases and clearance values in adolescents approach those observed in adults. Systemic exposure (mean daily area under the plasma concentration-time curve [AUC]) in pediatric patients younger than 12 years of age receiving linezolid every 8 hours generally is similar to that in adults and adolescents receiving the drug every 12 hours. There is wider intraindividual variability in linezolid clearance and in systemic drug exposure in all pediatric age groups relative to adults. Inadequate systemic exposure, site and severity of infection, and underlying medical conditions should be considered in children with a suboptimal response to linezolid, especially those with infections caused by gram-positive organisms that have minimum inhibitory concentrations (MICs) of 4 mcg/mL.

Geriatric Use

No substantial differences in safety and efficacy nor in pharmacokinetics relative to younger adults. Severe Renal Impairment Use with caution. Severe Hepatic Impairment Use with caution.

Common Adverse Effects

Adverse effects occurring in 2% or more of adults receiving linezolid include diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, and dizziness. Drug-related adverse effects reported in 1% or more of pediatric patients receiving linezolid in clinical studies include diarrhea, nausea, headache, thrombocytopenia, vomiting, abdominal pain, anemia, eosinophilia, rash, and vertigo.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely with drugs metabolized by hepatic microsomal (cytochrome P-450 [CYP]) enzymes such as phenytoin or warfarin.

Aztreonam and Gentamicin

Pharmacokinetic interaction unlikely.

Sympathomimetic Agents

Potential pharmacologic interaction (enhanced vasopressor effects) with sympathomimetic agents such as dopamine, epinephrine, phenylpropanolamine, or pseudoephedrine.

Serotonergic Agents

Potential pharmacologic interaction (serotonin syndrome). Although serotonin syndrome was not reported during clinical trials with linezolid, there have been a limited number of postmarketing case reports of the syndrome in patients who received linezolid concurrently with or shortly after discontinuation of certain selective serotonin-reuptake inhibitors (SSRIs) (e.g., citalopram, paroxetine, sertraline). Clinicians should consider the possibility if signs and symptoms of serotonin syndrome (e.g., hyperpyrexia, cognitive dysfunction) occur in patients receiving such concomitant therapy. Some clinicians suggest that linezolid be used with caution in patients receiving SSRIs, and some suggest that SSRI therapy should be discontinued before linezolid is initiated and not reinitiated until 2 weeks after linezolid therapy is completed. For further information on serotonin syndrome, including manifestations and treatment.

Description

Linezolid is a synthetic oxazolidinone anti-infective agent that is structurally unrelated to other anti-infectives commercially available in the US. In contrast to other anti-infectives that inhibit bacterial protein synthesis, linezolid acts early in translation by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit and preventing the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process.

Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Linezolid is active in vitro and in clinical infections against most strains of Enterococcus faecium (established in vancomycin-resistant strains only), Staphylococcus aureus (including oxacillin-resistant strains), Streptococcus agalactiae (group B streptococci), S. pneumoniae (established in penicillin-susceptible strains only), and S. pyogenes (group a b-hemolytic streptococci).

Linezolid also has demonstrated in vitro activity against Enterococcus faecalis (including vancomycin-resistant strains), E. faecium (vancomycin-susceptible strains), S. epidermidis (including oxacillin-resistant strains [previously known as methicillin-resistant strains]), S. haemolyticus, S. pneumoniae (penicillin-resistant strains), viridans group streptococci, and Pasteurella multocida; however, safety and efficacy of linezolid in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled clinical studies to date. Resistance to linezolid has been produced in vitro by serial passage of enterococci (i.e., E. faecalis, E. faecium) in the presence of increasing concentrations of the drug, and resistance to linezolid has emerged rarely in patients receiving the drug for the treatment of E. faecium or E. faecalis infections.

Strains of oxacillin-resistant S. aureus with decreased susceptibility to linezolid have been produced in vitro by serial passage on gradient plates, and resistant strains also have been isolated from a renal dialysis patient receiving the drug for the treatment of peritonitis caused by oxacillin-resistant S. aureus. The potential for cross-resistance between linezolid and other anti-infectives commercially available in the US is considered low because of the drug’s unique mechanism of action. Linezolid is well absorbed following oral administration (absolute bioavailability approximately 100%) and is readily distributed to well-perfused tissues. The drug is metabolized principally via oxidation to 2 inactive metabolites: an aminoethoxyacetic acid metabolite and a hydroxyethyl glycine metabolite. Linezolid is not metabolized to any measurable extent by the cytochrome P-450 (CYP) enzyme system.

Linezolid does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 and is not an enzyme inducer, suggesting that the drug is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.

Advice to Patients

Importance of avoiding excessive amounts (>100 mg per meal) of dietary tyramine while receiving linezolid. Phenylketonurics should be informed that linezolid oral suspension contains aspartame. Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. Importance of notifying clinicians of history of hypertension. Importance of monitoring for signs of hypersensitivity reaction. Importance of women informing clinicians if they are or plan to become pregnant or are breastfeeding.

Importance of completing the entire course of therapy even if symptoms improve within a few days. Importance of reporting persistent or worsening symptoms of infection. If using the oral suspension: once reconstituted, do not shake the bottle vigorously. Instead, gently invert the bottle 3-5 times to resuspend the drug prior to administration of each dose. Overview.

For additional information until a more detailed monograph is developed and published, the manufacturer’s labeling should be consulted. It is essential that the manufacturer’s labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Although a 400-mg tablet and a 400-mg premixed injection have been approved for marketing in the US and are described in the manufacturer’s labeling, the manufacturer states that these preparations are not currently available. Linezolid Oral For suspension 100 mg/5 mL Zyvox®, Pfizer Tablets, film- 600 mg Zyvox®,coated Pfizer Parenteral Injection, for IV 2 mg/mL (200 and 600 mg) in Zyvox® Injection, (in flexible infusion sterile isotonic solution containers) Pfizer