Zyrolin Powder for Suspension

Linezolid 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. Linezolid 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 Linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, Linezolid was found to be bactericidal for the majority of strains.

Linezolid tablets should be taken in oral route with or without food. Linezolid IV infusion should be administered by intravenous infusion over a period of 30 to 120 minutes. The recommended daily dosage for Linezolid tablets and IV infusion is described in the following table:

Infection	Dosage, route and frequency of administration
	Pediatric patients* (birth through 11 years of age)	Adults and adolescent (12 years and older)	Recommended duration of treatment (consecutive days)
Nosocomial pneumonia	10 mg/kg orally or intravenously every 8 hours	600 mg orally or intravenously every 12 hours	10 to 14
Community-acquired pneumonia, including concurrent bacteremia
Complicated skin and skin structure infections
Complicated skin and skin structure infections	10 mg/kg orally or intravenously every 8 hours	600 mg orally or intravenously every 12 hours	14 to 28
Uncomplicated skin and skin structure infections	less than 5 years: 10 mg/kg orally every 8 hours 5-11 years: 10 mg/kg orally every 12 hours	Adults: 400 mg orally every 12 hours Adolescents: 600 mg orally every 12 hours	10 to 14
* Neonates less than 7 days: Most pre-term neonates less than 7 days of age (gestational age less than 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 every 8 hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg every 8 hours by 7 days of life.

No dose adjustment is necessary when switching from intravenous to oral administration.

Intravenous administration: Linezolid IV infusion should be inspected visually against a light source for particulate matter prior to administration. Linezolid IV infusion may exhibit a yellow color that can intensify over time without adversely affecting potency. Do not use this intravenous infusion vial in series connections. Additives should not be introduced into this solution. Discard unused portion after single use.

Hepatic impairment: No dose adjustment is recommended for patients with mild-to-moderate hepatic impairment. The pharmacokinetics of Linezolid in patients with severe hepatic impairment have not been evaluated.

Use in children and adolescents: The dose of linezolid for children and adolescents have been described in dose and administration section. The use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended

Drug interaction with medication: Zyrolin is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, Zyrolin has the potential for interaction with adrenergic and serotonergic agents. Some individuals receiving Zyrolin may experience a reversible enhancement of the pressor response to indirect acting sympathomimetic agents, vasopressor or dopaminergic agents. Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, Zyrolin should not be administered to patients with carcinoid syndrome and/or patients taking serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

Drug interaction with food and others: Advice patients to avoid large quantities of foods or beverages with high tyramine content while taking Zyrolin.

Linezolid formulations are contraindicated for using in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid 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. Linezolid 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.

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

Pregnancy: Available data with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Linezolid is present in breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for linezolid and any potential adverse effects on the breastfed child from linezolid or from the underlying maternal condition. Advise lactating women to monitor a breastfed infant for diarrhea and vomiting.

Complete blood counts should be monitored weekly in patients who receive Zyrolin, particularly in those who receive Zyrolin for longer than two weeks, those with pre-existing myelosuppression, those receiving concomitant drugs that produce bone marrow suppression or those with a chronic infection who have received previous or concomitant antibiotic therapy. 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. Zyrolin is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. Careful medical history is necessary since Clostridium difficile-associated Diarrhea (CDAD) has been reported to occur over two months after antibiotic administration. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Unless patients are monitored for potential increases in blood pressure, Zyrolin should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking sympathomimetic agents, vasopressive agents and dopaminergic agents. Patients who develop recurrent nausea or vomiting, unexplained acidosis or low bicarbonate level while receiving Zyrolin should receive immediate medical evaluation. If hypoglycemia occurs, a decrease in the dose of insulin or oral hypoglycemic agent or discontinuation of oral hypoglycemic agent, insulin or Zyrolin may be required.

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

Macrolides

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled and cooled water to the dry mixture in the bottle. For the 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 each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place. Use within 21 days after constitution.

Intravenous Administration: Zyrolin IV Injection is supplied in single-use, ready-to-use infusion bottles. Zyrolin IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bottles should not be used in series connections. Additives should not be introduced into this solution. The infusion bottles should be stored at room temperature and protected from freezing. Zyrolin IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Zyrolin formulations should be stored at room temperature (15°C-30°C), away from light and moisture. All medicines should be kept away from children.