Nezocin

Uses

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 used 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)

Nezocin is also used to associated treatment for these conditions: Community Acquired Pneumonia (CAP) caused by Staphylococcus Aureus Infections, Community acquired pneumonia caused by Susceptible strains of Streptococcus pneumoniae, Complicated Skin and Skin Structure Infection caused by Staphylococcus Aureus Infections, Complicated Skin and Skin Structure Infection caused by Streptococcus Agalactiae Infection, Complicated Skin and Skin Structure Infection caused by Streptococcus Pyogenes Infection, Nosocomial Pneumonia caused by Staphylococcus Aureus Infections, Nosocomial Pneumonia caused by Streptococcus Pneumoniae Infections, Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus Aureus Infections, Uncomplicated Skin and Skin Structure Infections caused by Streptococcus Pyogenes Infection, Vancomycin-resistant Enterococcus faecium infection

How Nezocin works

Nezocin exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing.

Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant Enterococcus faecium and Staphylococcus aureus have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Dosage

Nezocin dosage

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 Nezocin 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.

Intravenous Administration: Nezocin 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. Nezocin 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. Nezocin IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

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 Nezocin 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.

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. 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.

Side Effects

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

Toxicity

Clinical signs of overdosage observed in rats were decreased activity and ataxia (2000 mg/kg/day) and in dogs were vomiting and tremors (3000 mg/kg/day). Treatment of overdose should involve symptomatic and supportive measures and may include hemodialysis if clinically necessary.

Precaution

Patients who develop recurrent nausea or vomiting, unexplained acidosis, or low bicarbonate level while receiving Nezocin should receive immediate medical evaluation. Where administration of Nezocin 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 Nezocin. In some of these cases, a history of seizures or risk factors for seizures was reported.

Interaction

Monoamine Oxidase Inhibition: Nezocin is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, Nezocin has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Nezocin 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 Nezocin and serotonergic agents.

Food Interaction

• Avoid tyramine-containing foods and supplements. Avoid food containing high amounts of tyramine (>100mg). Tyramine-containing foods include cheese, red wine, fava beans, pickled foods, cured foods, and alcoholic beverages.
• Take with or without food. Co-administration with food does not significantly alter the pharmacokinetics of linezolid.

[Major] CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs).

The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of MAOIs.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor.

These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements.

Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well.

At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed.

Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned.

Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

Nezocin Hypertension interaction

[Moderate] Nezocin should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and

Caution and close monitoring are recommended when prescribing this agent to these patients.

Nezocin Drug Interaction

Major: ondansetronModerate: fluticasone / salmeterol, diphenhydramine, albuterol / ipratropium, furosemide, metoprololUnknown: ciprofloxacin, sulfamethoxazole / trimethoprim, apixaban, ferrous sulfate, acetaminophen, clopidogrel, pantoprazole, acetaminophen, valproic acid, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol, phytonadione

Nezocin Disease Interaction

Major: colitis, bone marrow suppressionModerate: acidosis, carcinoid syndrome, hemodialysis, hypertension, hypoglycemia, liver disease, MAOI activity, neuropathy, renal dysfunction, seizures

Volume of Distribution

At steady-state, the volume of distribution of linezolid in healthy adults is approximately 40-50 liters.

Elimination Route

Nezocin is extensively absorbed following oral administration and has an absolute bioavailability of approximately 100%. Maximum plasma concentrations are reached within approximately 1 to 2 hours after dosing (T_max) and range from 8.1-12.9 mcg/mL after single doses and 11.0-21.2 mcg/mL after multiple dosing.

The absorption of orally administered linezolid is not significantly affected by co-administration with food and it may therefore be given without regard to the timing of meals.

Half Life

The elimination half-life is estimated to be between 5 and 7 hours.

Clearance

Total clearance of linezolid is estimated to be 100-200 mL/min, the majority of which appears to be non-renal. Mean renal clearance is approximately 40 mL/min, which suggests net tubular reabsorption, while non-renal clearance is estimated to account for roughly 65% of total clearance, or 70-150 mL/min on average. Variability in linezolid clearance is high, particularly for non-renal clearance.

Elimination Route

Urinary excretion is the primary means by which linezolid and its metabolic products are excreted. Following the administration of a radiolabeled dose of linezolid under steady-state conditions, approximately 84% of radioactivity was recovered in the urine, of which approximately 30% is unchanged parent drug, 40% is the hydroxyethyl glycine metabolite, and 10% is the aminoethoxyacetic acid metabolite. Fecal elimination is comparatively minor, with no parent drug observed in feces and only 6% and 3% of an administered dose found in the feces as the hydroxyethyl glycine metabolite and the aminoethoxyacetic acid metabolite, respectively.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Nezocin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Nezocin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nezocin is administered to a nursing woman.

Contraindication

Nezocin formulations are contraindicated for use in patients who have known hypersensitivity to Nezocin or any of the other product components. Nezocin should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product. Nezocin should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Acute Overdose

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

Storage Condition

Should be stored at room temperature 25° C, away from light and moisture.

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