Zyvoxid

/ Pfizer

Linezolid solution for infusion and film coated tablets may be used as initial therapy. Patients who commence treatment on the parenteral formulation may be switched to either oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as linezolid has an oral bioavailability of approximately 100%. The solution for infusion should be administered over a period of 30 to 120 minutes. The film coated tablets may be taken with or without food. The recommended linezolid dosage should be administered IV or orally twice daily.
Complicated skin and skin structure infections, Community-acquired pneumonia, including concurrent bacteremia, Nosocomial pneumonia:
Pediatric Patients† (Birth through 11 Years of Age), Adults and Adolescents (12 Years and Older): 10 mg/kg IV or oral^‡ q8h, recommended duration of treatment – 10 to 14 consecutive  days.
Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia:
Pediatric Patients† (Birth through 11 Years of Age), Adults and Adolescents (12 Years and Older): 10 mg/kg IV or oral^‡ q8h, recommended duration of treatment – 14to 28 consecutive days.
Uncomplicated skin and skin structure infections:
Pediatric Patients† (Birth through 11 Years of Age): <5 yrs: 10 mg/kg oral‡ q8h  5-11 yrs: 10 mg/kg oral^‡ q12h  – 10 to 14 consecutive  days.
Adults and Adolescents (12 Years and Older): Adults: 400 mg oral^‡ q12h. Adolescents: 600 mg oral^‡ q12h-  – 10 to 14 consecutive  days.
Due to the designated pathogens.
† 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. ‡ Oral dosing using linezolid Tablet.
Adult patients with infection due to MRSA should be treated with Linezolid 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 Linezolid 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.
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 I.V. Injection may be switched to Tablets at the discretion of the physician, when clinically indicated.
Elderly patients: No dose adjustment is required.
Female patients: No dose adjustment is required.
Patients with renal insufficiency: No dose adjustment is required .
Patients with mild to moderate renal insufficiency: (ie CLCR> 30 ml/min}: No dose adjustment is required.
Patients with severe renal insufficiency CLCR < 30 ml/min): No dose adjustment is required. Due to the unknown clinical significance of higher exposure (up to 10 fold) to the two primary metabolites of linezolid in patients with severe renal insufficiency, linezolid should be used with special caution in these patients and only when the anticipated benefit is considered to outweigh the theoretical risk. As approximately 30% of a linezolid dose is removed during 3 hours of hemodialysis, linezolid should be given after dialysis in patients receiving such treatment. The primary metabolites of linezolid are removed to some extent by hemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency. Therefore, linezolid should be used with special caution in patients with severe renal insufficiency who are undergoing dialysis and only when the anticipated benefit is considered to outweigh the theoretical risk. To date, there is no experience of linezolid administration to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than haemodialysis).
Patients with impaired hepatic function: No dose adjustment is required. However, there are no pharmacokinetic data and limited clinical experience of linezolid in patients with severe hepatic insufficiency. Linezolid should be used with special caution in patients with severe hepatic insufficiency and only when the anticipated benefit is considered to outweight the theoretical risk.

Therapy is indicated only when an organism resistant to all other antibiotics is suspected. Indicated in adult and pediatric patients for the treatment of infections when known or suspected to be caused by susceptible organisms including those associated with concurrent bacteraemia such as: Pneumonia – community acquired and nosocomial pneumonia including multi drug resistant streptococcus pneumonia (MDRSP). Skin and soft tissue infections including diabetic foot infections. Enterococcal  infections. Combination therapy may be indicated if a concomitant Gram negative pathogen is documented or suspected.

Hypersensitivity to linezolid or to any of the excipients.
Oxidase Inhibitors: Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, moclobemide) or within two weeks of taking any such medicinal product.
Potential Interactions Producing Elevation of Blood Pressure: Unless the patients are monitored for increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g., pseudoephedrine, phenylpropanolamine), vasopressive agents (e.g., epinephrine, norepinephrine), dopaminergic agents (e.g., dopamine, dobutamine).
Serotonergic Interactions: Patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5–HT1 receptor agonists (triptans), meperidine or buspirone.

Myelosuppression: Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected haematologic parameters have risen toward pretreatment levels. The risk of these effects appears to be related to the duration of treatment. Elderly patients treated with linezolid may be at greater risk of experiencing blood dyscrasias than younger patients. Thrombocytopenia may occur more commonly in patients with severe renal insufficiency, whether or not on dialysis, and in patients with moderate to severe hepatic impairment. Therefore, close monitoring of blood counts is recommended in patients who: have pre-existing anaemia, granulocytopenia or thrombocytopenia; are receiving concomitant medications that may decrease haemoglobin levels, depress blood counts or adversely affect platelet count or function; have severe renal insufficiency or moderate to severe hepatic impairment; receive more than 10-14 days of therapy. Linezolid should be administered to such patients only when close monitoring of haemoglobin levels, blood counts and platelet counts is possible.
If significant myelosuppression occurs during linezolid therapy, treatment should be stopped unless it is considered absolutely necessary to continue therapy, in which case intensive monitoring of blood counts and appropriate management strategies should be implemented.
In addition, it is recommended that complete blood counts (including haemoglobin levels, platelets, and total and differentiated leucocyte counts) should be monitored weekly in patients who receive linezolid regardless of baseline blood count.
Mortality imbalance in a clinical trial in patients with catheter-related Gram-positive bloodstream infections: In a clinical trial involving patients with catheter-related bloodstream infections, higher mortality was observed in those treated with linezolid compared to alternative treatments. This difference was mainly influenced by the type of infection present at the start of the study, particularly the presence of pathogens other than Gram-positive bacteria. Patients in the linezolid group were more likely to develop infections with Gram-negative or mixed organisms, which contributed to increased mortality. As a result, linezolid should only be used for complicated skin and soft tissue infections in patients with known or possible Gram-negative co-infection when no alternative treatment options are available. In such cases, appropriate Gram-negative coverage must be initiated at the same time.
Antibiotic-associated diarrhoea and colitis: If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including linezolid, should be discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.
Lactic acidosis: Lactic acidosis has been reported with the use of linezolid. Patients who develop signs and symptoms of metabolic acidosis including recurrent nausea or vomiting, abdominal pain, a low bicarbonate level, or hyperventilation while receiving linezolid should receive immediate medical attention. If lactic acidosis occurs, the benefits of continued use of linezolid should be weighed against the potential risks.
Rhabdomyolysis: Rhabdomyolysis has been reported with the use of linezolid. Linezolid should be used with caution in patients with pre-disposing factors for rhabdomyolysis. If signs or symptoms of rhabdomyolysis are observed, linezolid should be discontinued and appropriate therapy initiated.
Hyponatraemia and SIADH: Hyponatraemia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) have been observed in some patients treated with linezolid. It is recommended that serum sodium levels are monitored regularly in patients at risk of hyponatraemia such as elderly patients or patients taking medicines that may lower blood sodium levels (e.g. thiazide diuretics such as hydrochlorothiazide).
Peripheral and optic neuropathy: Peripheral neuropathy, as well as optic neuropathy and optic neuritis sometimes progressing to loss of vision, have been reported in patients treated with Linezolid; these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days. If used for over 28 days, visual function should be regularly monitored. An increased risk of neuropathies may occur when Linezolid is used with current or recent antimycobacterial treatment for tuberculosis.
Convulsions: Convulsions have been reported to occur in patients when treated with Linezolid. In most of these cases, a history of seizures or risk factors for seizures was reported.
Monoamine oxidase inhibitors: Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the doses used for antibacterial therapy, it does not exert an anti-depressive effect. There are very limited data from drug interaction studies and on the safety of linezolid when administered to patients with underlying conditions and/or on concomitant medications which might put them at risk from MAO inhibition. Therefore, linezolid is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible.
Use with tyramine-rich foods: Should be advised against consuming large amounts of tyramine-rich foods
Clinical trials: The safety and effectiveness of linezolid when administered for periods longer than 28 days have not been established.
Controlled clinical trials did not include patients with diabetic foot lesions, decubitus or ischaemic lesions, severe burns or gangrene. Therefore, experience in the use of linezolid in the treatment of these conditions is limited.
See prescribing information for full details.

Abdominal pain/cramps/distension, diarrhea, nausea, vomiting.
See prescribing information for full details.

Linezolid is not detectably metabolised by the cytochrome P450 (CYP) enzyme system and it doesn’t  induse or inhibit  the activities of clinically significant human CYP Isoforms (lA2, 2C9, 2C19, 2D6, 2El, 3A4).
See prescribing information for full details.  

Pregnancy: There are limited   data from the use of linezolid in pregnant women.
Lactation: Breast feeding should be discontinued prior to administration of linezolid.
See prescribing information for full details.

No cases of overdose have been reported. However, the following information may prove useful: Supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a linezolid dose is removed during 3 hours of haemodialysis, but no data are available for the removal of linezolid by peritoneal dialysis or haemoperfusion. The primary metabolites of linezolid are also removed by haemodialysis. Signs of toxicity in rats following doses of 3000 mg/kg/day linezolid were decreased activity and ataxia whilst dogs treated with 2000 mg/kg/day experienced vomiting and tremors.

Storage: Solution for injection: store below 25°C.