Linzolid(Linezolid)

Therapeutic Group: Anti Bacterial

Presentation

Linzolid 400 Tablet: Each film-coated tablet contains Linezolid INN 400 mg.

Linzolid 600 Tablet: Each film-coated tablet contains Linezolid INN 600 mg.

Linzolid Powder for Suspension: After reconstitution, according to direction, each 5 ml suspension contains Linezolid INN 100 mg.

Linzolid 600 IV Infusion: Each 300 ml solution contains Linezolid INN 600 mg.

Linzolid 200 IV Infusion: Each 100 ml solution contains Linezolid INN 200 mg

Description

Linzolid (Linzolid) is a synthetic, antibacterial agent belonging to a new class of antibiotics, the oxazolidinones, with in vitro activity against Gram positive aerobic bacteria, some Gram positive anaerobic bacteria and certain Gram negative bacteria. It selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. Linzolid binds to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome and prevents the formation of a functional 70S initiation complex which is an essential component of the bacterial translation process. The results of time-kill studies have shown Linzolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linzolid was found to be bactericidal for the majority of strains.

Indications

• 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). Combination therapy may be clinically indicated if the documented or presumptive pathogens include Gram-negative organism.

• 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.

• 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) including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only)

Dosage & Administration

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 Linzolid (Linezolid) has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film coated tablets or oral suspension may be taken with or without food.
Adults and Adolescents (12 Years and Older):

• Complicated skin and skin structure infections & Community-acquired pneumonia, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 10 to 14 days.
• Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 14-28
For Pediatric Patients (Birth through 11 Years of Age):
• Complicated skin and skin structure infections & Community-acquired pneumonia, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 10 to 14 days.
• Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia: 600 mg IV or oral b.i.d.for 14-28.
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 every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

Side Effects

Most of the adverse events reported with Linzolid were mild to moderate in intensity. The most common adverse events in patients treated with Linzolid were diarrhea, headache and nausea. Other adverse included oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Precautions

Patients who develop recurrent nausea or vomiting, unexplained acidosis, or low bicarbonate level while receiving Linzolid should receive immediate medical evaluation. Where administration of Linzolid and concomitant serotonergic agents is clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyper reflexia and incoordination. If signs or symptoms occur physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linzolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

Use in Pregnancy & Lactation

Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linzolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: It is not known whether Linzolid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Linzolid is administered to a nursing woman.

Drug Interaction

Monoamine Oxidase Inhibition: Linzolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, Linzolid has the potential for interaction with adrenergic and serotonergic agents.
Adrenergic Agents: Some individuals receiving Linzolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.
Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linzolid and serotonergic agents.

Over Dose

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linzolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linzolid by peritoneal dialysis or haemoperfusion.

Storage

Linzolid formulations should be stored at room temperature 25 °C, away from light and moisture. All medicines should be kept away from children.

Commercial Pack

Linzolid 400 Tablet: Each box contains 10 tablets in a blister strip.

Linzolid 600 Tablet: Each box contains 10 tablets in a blister strip.

Linzolid Powder for Suspension: After reconstitution, according to direction, each bottle contains 100 ml suspension.
Linzolid 600 IV Infusion: Each box contains 1 bottle of 300 ml solution for IV infusion, one infusion set & a hanger.
Linzolid 200 IV Infusion: Each box contains 1 bottle of 100 ml solution for IV infusion, one infusion set & a hanger.

Others

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled & cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.
Note: Shake the suspension well before use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool & dry place. Use within 21 days after reconstitution.

Intravenous Administration: Linzolid IV Injection is supplied in single-use, ready-to-use infusion bags. Parenteral drug products should be inspected visually for particulate matter prior to administration. Minute leaks should be checked by firmly squeezing the bag. If leaks are detected, the solution should be discarded, as sterility may be impaired. Linzolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bag should not be used in series connections. Additives should not be introduced into this solution. The infusion bag should be stored at room temperature and protected from freezing. Linzolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.