Loxenil

Each film coated tablet contains 600 mg of Linezolid.

Pharmacology: Pharmacodynamics: Antimicrobial Action: Linezolid is an oxazolidinone antibacterial with activity against a range of aerobic Gram-positive bacteria including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. It is less active against Gram-negative bacteria, but has some in-vitro activity against Haemophilus influanzae, spp., (Branhamella catarrhalis) and Pasteurella spp. It is not active against Acinetobacter spp., Enterobacteriaceae, or Pseudomonas spp. Oxazolidinone antibacterials are bacteriostatic and act by inhibition of ribosomal protein synthesis. Cross-resistance between oxazolidinones and other classes of antibacterial is considered unlikely. Resistant strains of enterococci and methicillin-resistant Staph. aureus have been reported.
Pharmacokinetics: Linezolid is rapidly and extensively absorbed after oral doses and maximum plasma concentrations are achieved after 1 to 2 hours. It is about 31% bound to plasma proteins. Linezolid is reported to be distributed into bone, fat, lungs, muscle, skin blister fluids, and into the CSF. It is metabolised mainly by oxidation to 2 main inactive metabolites, the hydroxyethyl glycine metabolite (PNU-142586) and the aminoethoxyacetic acid metabolite (PNU-142300); other minor inactive metabolites have also been identified. About 40% of a dose is excreted in the urine as PNU-142586, 30% as linezolid, and 10% as PNU-142300. Small amounts of metabolites are excreted in the faeces. The elimination half-life of linezolid is about 5 to 7 hours. Children exhibit more rapid clearance of linezolid than adults; half-life is reported to range from about 2 to 4 hours, increasing with age.

Treatment of the following infections caused by susceptible strains of the designated microorganisms. Linezolid is not indicated for the treatment of gram-negative infections. It is critical that specific gram-negative therapy may be initiated immediately if a concomitant gram-negative pathogen is documented or suspected.
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 multidrug resistant trains (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. Linezolid has not been studied in the treatment of decubitus ulcers.
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes.
Community-acquired pneumonia caused by Streptococcus pneumoniae [including multidrug 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 Linezolid and other antibacterial drugs, Linezolid 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.
*MDRSP refers to isolates resistant to ≥2 of the following antibiotics: Penicillin, 2nd-generation cephalosporins, macrolides, tetracycline and trimethoprim/sutfamethoxazole.

Adult patients with infection due to Methicillin-resistant Staphylococcus aureus (MRSA) should be treated with Linezolid 600 mg every 12 hrs. In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to gram-positive pathogens with MICs of 4 mcg/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 suboptimal clinical response, particularly those with pathogens with MIC of 4 mcg/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 7-28 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. May be taken with or without meal.
The recommended dosage for Linezolid formulations for the treatment of infections is described in the table below.

Click on icon to see table/diagram/image

Hypersensitivity to linezolid or any of the other components of Linezolid.
Monoamine Oxidase lnhibitors: Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (eg, phenelzine, isocarboxazid) or within 2 weeks of taking any such medicinal product.
Potential Interactions Producing Elevation of Blood Pressure: Unless patients are monitored for potential 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 (eg, pseudoephedrine), vasopressive agents (eg, epinephrine, norepinephrine), dopaminergic agents (eg, dopamine, dobutamine).
Potential Serotonergic Interactions: Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: Serotonin re-uptake inhibitors, bicyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Myelosuppression (including anemia, leukopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pre-treatment levels. Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for >2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression. In adult and juvenile dogs and rats, myelosuppression, reduced extramedullary hematopoiesis in spleen and liver and lymphoid depletion of thymus, lymph nodes and spleen were observed Mortality Imbalance in an lnvestigational Study in Patients with Catheter-Related Bloodstream Infections, Including Those with Catheter-Site Infections: An imbalance in mortality was seen in patients treated with linezolid relative to vancornycin / dicloxacillin / oxacillin in an open-label study in seriously ill patients with intravascular catheter-related infections [78/363 (21.5%) vs 58/363 (16%); odds ratio 1.426, 95% CI 0.97, 2.098]. While causality has not been established, this observed imbalance occurred primarily in linezolid-treated patients in whom either gram-negative pathogens, mixed gram-negative and gram-positive pathogens, or no pathogen were identified at baseline, but was not seen in patients with gram-positive infections only. Linezolid is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. Linezolid has no clinical activity against gram-negative pathogens and 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 Indications). Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zyvox, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile and surgical evaluation should be instituted as clinically indicated. Hypoglycemia: Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents when treated with linezolid, a reversible, nonselective MAO inhibitor. Some MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or hypoglycemic agents. While a causal relationship between linezolid and hypoglycemia has not been established, diabetic patients should be cautioned of potential hypoglycemic reactions when treated with linezolid. If hypoglycemia occurs, a decrease in the dose of insulin or oral hypoglycemic agent, or discontinuation of oral hypoglycemic agent insulin or linezolid may be required.

The adverse effects most frequently reported in patients given linezolid include diarrhoea, nausea and vomiting, metallic taste, headache, insomnia, constipation, rashes, dizziness, fever, oral and vaginal candidiasis, and abnormal liver function tests. Lactic acidosis has been reported. Convulsions have also been reported in patients treated with linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported. There have been rare reports of bullous skin eruptions including Stevens-Johnson syndrome. Peripheral and optic neuropathy, sometimes progressing to loss of vision, have occurred rarely, mainly in patients given linezolid for more than 28 days. Visual blurring has been reported in some patients given less than 28 days of treatment. Reversible myelosuppression including anaemia, leucopenia, pancytopenia and, in particular, thrombocytopenia has been reported and blood counts should be monitored weekly in patients receiving linezolid. Patients particularly at risk are those who have received linezolid for more than 10 to 14 days, who are receiving other bone marrow suppressant drugs, or who have pre-existing myelosuppression or severe renal impairment. Patients with mixed (Gram-negative and Gram-positive) infections are at a higher risk of mortality when linezolid is given as monotherapy; linezolid must therefore be used with appropriate antibacterial cover.

Linezolid is a reversible, nonselective MAOI and therefore has the potential to interact with adrenergic and serotonergic drugs. Enhanced pressor activity has been reported in patients receiving linezolid with phenylpropanolamine or pseudoephedrine and initial doses of dopamine or adrenaline should be reduced. There have also been cases of serotonin syndrome when linezolid was taken with serotonin reuptake inhibitors and similar symptoms when it was taken with dextromethorphan. The interactions of conventional MAOIs, both with other drugs and with foods, are described under Phenelzine.

Store at temperatures not exceeding 30°C.

Other Antibiotics

J01XX08 - linezolid ; Belongs to the class of other antibacterials. Used in the systemic treatment of infections.

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