Each film-coated tablet contains Linezolid 600 mg.
Pharmacology: Pharmacodynamics: Linezolid is an oxazolidinone anti-infective agent. Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, Linezolid makes unlikely cross-resistance with other drug classes.
The mechanism of action of Linezolid involves binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevention of formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. (Linezolid binds selectively to the 50s ribosomal subunit.) Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci.
Linezolid is active in vitro against most strains of Staphylococcus aureus (including methicillin resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), Streptococcus agalactiae (group B streptococci, GBS), S. pneumoniae, S. Pyogenes (group A b-hemolytic streptococci, GAS), and vancomycin resistant Enterococcus faecium. Linezolid also has in vitro activity against E. faecalis (including vancomycin-resistant strains), E. faecium (vancomycin-susceptible strains), S. epidermidis (including methicillin-resistant strains [oxacillin-resistant strains]), S. haemolyticus, viridans group streptococci, group G streptococci, Corynebacterium, and Pasteurella multocida.
Resistant to Linezolid has been produced in vitro by serial passage of MRSA (methicillin-resistant Staphylococcus aureus) or enterococci (i.e. E. faecium and E. faecalis).
Pharmacokinetics: Linezolid is well absorbed following oral administration. Peak plasma concentrations occur after 1 to 2 hours. The absolute oral bioavailability is ~ 100%.
Linezolid is readily distributed to well-perfused tissues. Linezolid's volume of distribution at steady state is 40-50 L. It is about 31% bound to plasma protein.
Linezolid is metabolized principally via oxidation to 2 inactive metabolites (an aminoethoxyacetic acid metabolite and a hydroxyethyl glycine metabolite). Linezolid is minimally metabolized and metabolism may be mediated by the cytochrome P-450 (CYP) enzyme system.
Linezolid is eliminated in urine as unchanged drug approximately 30% of an administered dose, as its metabolites approximately 50% of an administered dose and in feces as its metabolites approximately 9% of an administered dose.
Non-renal clearance is approximately 65% of total clearance of Linezolid.
The elimination half-life of Linezolid is 1.5-3 hours for children (1 week-11 years) and 4-5 hours for adults.
Linezolid is active against most gram positive bacteria including MRSA, streptococci and VRE. The drug approved for the treatment of VRE infections.
Linezolid is a not preferred agent in treatment of infections requiring prolonged therapy (i.e. > 2 weeks) due to the risk of serious hematologic and neurologic toxicity. Use of Linezolid is generally reserved for treatment of infections due to drug-resistant organisms (e.g. MRSA, VRE).
Community-acquired pneumonia: Treatment of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only).
Nosocomial pneumonia (hospital-acquired or healthcare-associated pneumonia): Treatment of nosocomial pneumonia (hospital-acquired or healthcare-associated pneumonia) caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), or Streptococcus pneumoniae.
Uncomplicated skin and skin structure infections: Treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes.
Complicated skin and skin structure infections (including diabetic foot infections), without concurrent osteomyelitis: Treatment of complicated skin and skin structure infections (including diabetic foot infections), without concurrent osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. The use of linezolid in the treatment of decubitus ulcers has not been studied.
Vancomycin-resistant Enterococcus faecium (VRE) infections: Treatment of vancomycin-resistant Enterococcus faecium (VRE) infections, including cases with concurrent bacteremia.
Linezolid is administered orally. Linezolid may be given without regard to meals.
Adult: (See Table 1).
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Pediatric: (See Table 2).
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Neonates: Most preterm neonates younger than 7 day of age (gestational age younger than 34 weekห) have lower systemic linezolid clearance values and larger area under the curve (AUC) value than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of a 10 mg/kg every 8 hours regimen in neonates with a suboptimal clinical response. All neonatal patients should receive 10 mg/kg every 8 hours by 7 days of life.
Administration in special patient population: Pediatric use:
The maximum plasma concentration (Cmax
) and the volume of distribution of Linezolid are similar regardless of age in children. Weight-based clearance varies as a function of age. Weight-based clearance is most rapid in children older than 1 week to 11 years of age, resulting in lower area under the curve (AUC) and shorter half-life compared with adults. By adolescence, mean clearance values approach those observed in the adult population. Preterm (less than 34 weeks gestational age) neonates less than 7 days of age may have lower clearance than full-term neonates less than 7 days of age and may require less frequent dosing.
No overall differences in safety, efficacy or pharmacokinetics have been observed in geriatric adults 65 years of age or older compared with younger adults. Dosage adjustments are not necessary in patients.
Patients with hepatic impairment:
Dosage adjustments are not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B). Data are not available regarding the pharmacokinetics of Linezolid in patients with severe hepatic impairment.
Patients with renal impairment:
Pharmacokinetics of Linezolid are not altered in patients with renal insufficiency. Linezolid requires no dose adjustment in renal failure. The two principal metabolites of Linezolid may accumulate in patients with renal impairment and the clinical importance of accumulation of these metabolites has not been determined. Approximately 30% of a dose is eliminated in a 3-hour dialysis session. Because Linezolid is removed by hemodialysis, patients undergoing hemodialysis should receive Linezolid doses after the dialysis session.
According to one study, the use of the standard dose of 600 mg every 12 hours for patients weighing 150 kg or less will provide AUC values similar to that seen in non-obese adult patients; patients weighing more than 150 kg were not included in the study.
Human overdose information is limited. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
There is no specific antidote for Linezolid. Symptomatic and supportive treatment should be provided.
Hypersensitivity to Linezolid or any ingredient in the formulation.
Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 2 weeks of MAOIs.
Hematologic effect: reversible myelosuppression (e.g. anemia, leukopenia, pancytopenia, thrombocytopenia) has been reported in patient receiving Linezolid. In cases where the outcome is known, when Linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood cell counts (CBCs) should be monitored weekly during Linezolid treatment, especially in patients receiving the drug for more than two weeks and in those who have preexisting myelosuppression, are receiving concomitant drugs that produce bone marrow suppression, or have a chronic infection that was or is being treated with concomitant anti-infective therapy.
Discontinuation of therapy with Linezolid should be considered in patients who develop or have worsening myelosuppression. Thrombocytopenia is the most frequently observed blood dyscrasia. The platelet counts for most patients returned to the normal range/baseline during the follow-up period.
Peripheral and optic neuropathy: Peripheral and optic neuropathies have been reported in adults and children receiving Linezolid; these events have occurred principally in patients receiving the drug for longer than the maximum recommended duration of treatment (28 days). All patients receiving Linezolid for extended periods of time (i.e. 3 months or longer) should have their visual function monitored.
Serotonin Syndrome: Serotonin syndrome (including some fatalities) has been reported in patients receiving Linezolid concomitantly with serotonergic drugs. Sign and symptoms of serotonin syndrome include mental changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering, shaking, diarrhea, loss of coordination, and/or fever.
Linezolid should not be used in patients with carcinoid syndrome or in patients receiving SSRIs, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, bupropion, or buspirone unless concomitant therapy is considered clinically appropriate and patients can be carefully monitored for signs and/or symptoms of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Superinfection/Clostridium difficile-associated diarrhea and colitis: Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile, C. Difficile infection (CDI) and C. Difficile-associated diarrhea and colitis (CDAD) have been reported with nearly all anti-infectives, including Linezolid, and may range in severity from mild diarrhea to fatal colitis. Therefore, If CDAD is suspected or confirmed, anti-infective therapy not directed against C. Difficile should be discontinued whenever possible.
Unless patients are monitored for potential increases in blood pressure, Linezolid should not be used in patients with uncontrolled hypertension, pheochromocytoma, or thyrotoxicosis or in patients receiving direct or indirect-acting sympathomimetic agents, vasopressor agents, or dopaminergic agents.
Lactic acidosis 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.
Seizure have been reported in patients receiving Linezolid. Some cases were reported in patients with a history of seizures or risk factors of seizures.
Symptomatic hypoglycemia has been reported in patients with diabetes mellitus receiving Linezolid concomitantly with insulin or oral antidiabetic agents. Use with caution and closely monitor glucose in diabetic patients.
Pregnancy: Pregnancy category C.
Adverse effects were observed in some animal reproduction studies at dose that were also maternally toxic.
Information related to Linezolid use during pregnancy is limited. Linezolid should be used during pregnancy only if potential benefits justify potential risk to the fetus.
Lactation: Linezolid is excreted into breast milk. Linezolid should be used with caution in nursing woman.
Undesirable effects from the use of Linezolid may occur; Central nervous system:
headache, dizziness, insomnia, vertigo.
diarrhea, abdominal pain, constipation, dysgeusia, increased serum lipase, loose stool, nausea, oral candidiasis, pancreatitis, tongue discoloration, vomiting.
Hematologic & Oncologic:
decreased hemoglobin, leukopenia, thrombocytopenia, anemia, eosinophilia, neutropenia.
pruritus, skin rash.
Endocrine & Metabolic:
increased amylase, increased lactate dehydrogenase.
abnormal hepatic function tests, increased serum ALT, increased serum AST (adults), increased serum alkaline phosphatase, increased serum bilirubin.
increased blood urea nitrogen, increased serum creatinine.
Rare but important or life-threatening:
hypertension, convulsions, peripheral neuropathy, seizure, serotonin syndrome, bullous skin disease, Stevens-Johnson syndrome, hypoglycemia, lactic acidosis, Clostridium difficile
-associated diarrhea, dental discoloration, pancytopenia, anaphylaxis, angioedema, rhabdomyolysis, blurred vision, optic neuropathy, vision loss.
Metabolism/transport effects: Linezolid inhibits monoamine oxidase and may interact with drugs that are metabolized by monoamine oxidase. Avoid concomitant use of Linezolid with any of the following: alcohol (ethyl), apraclonidine, atomoxetine, atropine (ophthalmic), BCG (intravesical), bezafibrate, buprenorphine, bupropion, buspirone, carbamazepine, cyclobenzaprine, cyproheptadine, dapoxetine, deferiprone, dexmethylphenidate, dextromethorphan, diethylpropion, dipyrone, epinephrine (oral inhalation), fentanyl, hydromorphone, isometheptene, levonordefrin, MAO inhibitors, maprotiline, meperidine, mequitazine, methyldopa, methylene blue, methylphenidate, mianserin, mirtazapine, moclobemide, morphine (liposomal), morphine (systemic), nefazodone, nefopam, oxymorphone, pholcodine, pizotifen, reboxetine, selective serotonin reuptake inhibitors, serotonin 5-HT1D receptor agonists, serotonin/norepinephrine reuptake inhibitors, tapentadol, tetrabenazine, tetrahydrozoline (nasal), tianeptine, trazodone, tricyclic antidepressant, tryptophan.
Importance of avoiding large quantities of foods or beverages with high tyramine content during Linezolid treatment; this includes foods or beverages that have been aged, fermented, pickled, or smoked to improve flavor (e.g., aged cheeses, fermented or air-dried meats, sauerkraut, soy sauce and other soybean condiments, tap beer, red wine). Consider that tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated.
J01XX08 - linezolid ; Belongs to the class of other antibacterials. Used in the systemic treatment of infections.
Tab 600 mg (white, oval and biconvex with "Click on icon to see table/diagram/image
" embossed on one side and a score with "L" and "600" on the other side) x 1 x 10's.