Composition:
active substance: linezolid;
1 ml of solution contains 2 mg of linezolid;
excipients: anhydrous glucose, sodium citrate, citric acid, monohydrate, sodium hydroxide, hydrochloric acid, water for injection.

Pharmaceutical form. Solution for infusion.
Basic physical and chemical properties: a clear, pale yellow solution

Pharmacotherapeutic group. Antibacterial agents for systemic use. Other antibacterial agents.
ATC code J01X X08.

Pharmacological properties.
Pharmacodynamics.
Linezolid is a synthetic, antibacterial agent that belongs to a new class of antimicrobials, the oxazolidinones. It has in vitro activity against aerobic Gram positive bacteria and anaerobic microorganisms. Linezolid selectively inhibits bacterial protein synthesis via a unique mechanism of action. Specifically, it binds to a site on the bacterial ribosome (23S of the 50S subunit) and prevents the formation of a functional 70S initiation complex which is an essential component of the translation process. The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Susceptible organisms
Gram positive aerobes: Enterococcus faecalis, Enterococcus faecium*, Staphylococcus aureus*, coagulase negative staphylococci, Streptococcus agalactiae*, Streptococcus pneumoniae*, Streptococcus pyogenes*, Group C streptococci, Group G streptococci.
Gram positive anaerobes: Clostridium perfringens, Peptostreptococcus anaerobius, Peptostreptococcus species.
Resistant organisms: Haemophilus influenza, Moraxella catarrhalis, Neisseria species, Enterobacteriaceae, Pseudomonas species.
* Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications.
Whereas linezolid shows some in vitro activity against Legionella, Chlamydia pneumoniae and Mycoplasma pneumoniae, there are insufficient data to demonstrate clinical efficacy.
Cross resistance
Linezolid's mechanism of action differs from those of other antibiotic classes. In vitro studies with clinical isolates (including methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin- and erythromycin-resistant streptococci) indicate that linezolid is usually active against organisms which are resistant to one or more other classes of antimicrobial agents.
Resistance to linezolid is associated with point mutations in the 23S rRNA.
Pharmacokinetics.
Linessa contains linezolid which is biologically active and is metabolised to form inactive derivatives.
Absorption
Linezolid is rapidly and extensively absorbed following oral dosing. Maximum plasma concentrations are reached within 1 to 2 hours of dosing. Absolute bioavailability of linezolid is approximately 100%. Therefore, linezolid can be orally or intravenously administered without dose adjustment.
Linezolid can be used regardless of food intake. The time to reach maximum plasma concentration increases from 1.5 to 2.2 hours, and C_max is reduced by about 17% when using linezolid with high-fat food. However, the total exposure estimated as rep AUC_0‑¥, is similar in both cases.
Distribution
Pharmacokinetic studies have shown that linezolid is rapidly distributed in tissues with good perfusion. Plasma protein binding is about 31% and is not concentration dependent. Volume of distribution at steady-state averages at about 40-50 litres in healthy adults
Linezolid concentrations have been determined in various fluids from a limited number of subjects in phase 1 studies following multiple dosing. The ratio of linezolid in saliva and sweat relative to plasma was 1.2:1.0 and 0.55:1.0, respectively..
Biotransformation
Linezolid is primarily metabolised by oxidation of the morpholine ring resulting mainly in the formation of two inactive open-ring carboxylic acid derivatives; the aminoethoxyacetic acid metabolite (A) and the hydroxyethyl glycine metabolite (B). Metabolite A is believed to be formed by an enzymatic process, whereas the formation of metabolite B is mediated by a non-enzymatic mechanism involving chemical oxidation in vitro. In vitro studies have shown that linezolid is minimally metabolized with the possible involvement of the human cytochrome P450 system in this process. However, the metabolic ways for linezolid have not been fully studied.
Elimination
Non-renal clearance accounts for approximately 65% of the total clearance of linezolid. Under steady-state conditions, approximately 30% of the dose is found as linezolid, 40% – as metabolite B and 10% – as metabolite A. The average renal clearance of linezolid is 40 ml/min, indicating tubular reabsorption. Linezolid is not nearly found in the faeces, whereas approximately 6% of the dose is found in the faeces as metabolite B and 3% – as metabolite A.
A small degree of non-linearity in clearance is observed with increasing doses of linezolid. This appears to be due to lower renal and nonrenal clearance at higher linezolid concentrations. However, the difference in clearance is small and is not reflected in the apparent elimination half-life.
Renal impairment. Linezolid pharmacokinetics are not altered in patients with any stage of renal failure; however, two major metabolites of linezolid are accumulated in patients with renal failure including increased accumulation in patients with greater severity of renal dysfunction. Linezolid pharmacokinetics and its two metabolites have also been studied in haemodialysis patients with end-stage renal failure. In end-stage renal failure study, 14 patients received 600 mg of linezolid every 12 hours for 14.5 days. Regardless of kidney function, the same plasma concentrations of linezolid were achieved, so no dose adjustment is recommended for patients with renal impairment. However, given the lack of information on the clinical relevance of the major metabolites accumulation, the use of linezolid in patients with renal impairment and the potential risks of accumulation of such metabolites should be considered. Both linezolid and two metabolites are eliminated by haemodialysis. There is no information on the effect of peritoneal dialysis on linezolid pharmacokinetics.
Hepatic impairment. Linezolid pharmacokinetics is not altered in 7 patients with mild to moderate hepatic insufficiency (i.e. Child-Pugh class A or B). Based on available data, no dose adjustment is recommended for patients with mild to moderate hepatic insufficiency. The pharmacokinetics of linezolid in patients with severe hepatic insufficiency has not been evaluated.

Clinical particulars.
Indications.
Treatment of infections caused by of anaerobic or aerobic gram-positive susceptible strains, including infections accompanied by bacteraemia, such as:
- nosocomial pneumonia;
- community acquired pneumonia;
- complicated infections of the skin and its structures, including infections due to diabetic foot without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes or Streptococcus agalactiae;
- uncomplicated infections of the skin and its structures caused by Staphylococcus aureus (methicillin isolates only) or Streptococcus pyogenes;
- enterococcal infections, including vancomycin resistant strains Enterococcus faecium or faecalis.
If infectious agents include gram-negative bacteria, the combination therapy is clinically indicated.

Contraindications.
Hypersensitivity to linezolid or to any of the excipients.
Linessa should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of taking any such medicinal product.
Unless there are facilities available for close observation and monitoring of blood pressure, Linessa should not be administered to patients with the following underlying clinical conditions or on the following types of concomitant medications:
- patients with uncontrolled hypertension, phaeochromocytoma, carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder, acute confusional states;
- serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT₁ receptor agonists (triptans), directly and indirectly acting sympathomimetic agents (including the adrenergic bronchodilators, pseudoephedrine and phenylpropanolamine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), pethidine or buspirone..
Breastfeeding should be discontinued during the drug administration (see section “Pregnancy and lactation”).

Precautions for use.
Myelosuppression
Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving linezolid. When linezolid was discontinued, the affected haematologic parameters have risen toward pretreatment levels. The risk of these effects appears to be related to the duration of treatment. Elderly patients treated with linezolid may be at greater risk of experiencing blood dyscrasias than younger patients. Thrombocytopenia may occur more commonly in patients with severe renal insufficiency, whether or not on dialysis. Therefore, close monitoring of blood counts is recommended in patients who: have pre-existing anaemia, granulocytopenia or thrombocytopenia; are receiving concomitant medications that may decrease haemoglobin levels, depress blood counts or adversely affect platelet count or function; have severe renal insufficiency; receive more than 10-14 days of therapy. Linezolid should be administered to such patients only when close monitoring of haemoglobin levels, blood counts and platelet counts is possible.
If significant myelosuppression occurs during linezolid therapy, treatment should be stopped unless it is considered absolutely necessary to continue therapy, in which case intensive monitoring of blood counts and appropriate management strategies should be implemented.
In addition, it is recommended that complete blood counts (including haemoglobin levels, platelets, and total and differentiated leucocyte counts) should be monitored weekly in patients who receive linezolid regardless of baseline blood count.
In compassionate use studies, a higher incidence of serious anaemia was reported in patients receiving linezolid for more than the maximum recommended duration of 28 days. These patients more often required blood transfusion. Cases of anaemia requiring blood transfusion have also been reported post marketing, with more cases occurring in patients who received linezolid therapy for more than 28 days.
Cases of sideroblastic anaemia have been reported post-marketing. Where time of onset was known, most patients had received linezolid therapy for more than 28 days. Most patients fully or partially recovered following discontinuation of linezolid with or without treatment for their anaemia.
Mortality imbalance in a clinical trial in patients with catheter-related Gram positive bloodstream infections
Excess mortality was seen in patients treated with linezolid, relative to vancomycin/dicloxacillin/oxacillin, in an open-label study in seriously ill patients with intravascular catheter-related infections [78/363 (21.5%) vs 58/363 (16.0%)]. The main factor influencing the mortality rate was the Gram positive infection status at baseline. Mortality rates were similar in patients with infections caused purely by Gram positive organisms (odds ratio 0.96; 95% confidence interval: 0.58-1.59) but were significantly higher (p=0.0162) in the linezolid arm in patients with any other pathogen or no pathogen at baseline (odds ratio 2.48; 95% confidence interval: 1.38- 4.46). The greatest imbalance occurred during treatment and within 7 days following discontinuation of study drug. More patients in the linezolid arm acquired Gram negative pathogens during the study and died from infection caused by Gram negative pathogens and polymicrobial infections. Therefore, in complicated skin and soft tissue infections linezolid should only be used in patients with known or possible co-infection with Gram negative organisms if there are no alternative treatment options available (see section “Indications”). In these circumstances treatment against Gram negative organisms must be initiated concomitantly.
Antibiotic-associated diarrhoea and colitis
Antibiotic-associated diarrhoea and antibiotic-associated colitis, including pseudomembranous colitis and Clostridium difficile-associated diarrhoea, has been reported in association with the use of nearly all antibiotics including linezolid and may range in severity from mild diarrhoea to fatal colitis. Therefore, it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of linezolid. If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including linezolid, should be discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.
Lactic acidosis
Lactic acidosis has been reported with the use of linezolid. Patients who develop signs and symptoms of metabolic acidosis including recurrent nausea or vomiting, abdominal pain, a low bicarbonate level, or hyperventilation while receiving linezolid should receive immediate medical attention. If lactic acidosis occurs, the benefits of continued use of linezolid should be weighed against the potential risks.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis. Adverse events, such as lactic acidosis, anaemia and neuropathy (optic and peripheral), may occur as a result of this inhibition; these events are more common when the drug is used longer than 28 days.
Potential interactions producing elevation of blood pressure
Unless the cases when monitoring patients for the suggested elevation of blood pressure is available, linezolid should not be administered to patients with uncontrolled arterial hypertension, pheochromocytoma, thyrotoxicosis and/or concomitant use of such types of drugs as: direct and indirect sympathomimetics (pseudoephedrine), vasopressors (epinephrine, norepinephrine), dopaminergic agents (dopamine, dobutamine).
Serotonin syndrome
Spontaneous reports of serotonin syndrome associated with the co-administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been reported. Co-administration of linezolid and serotonergic agents is therefore contraindicated (see section 4.3) except where administration of linezolid and concomitant serotonergic agents is essential. In those cases patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur physicians should consider discontinuing either one or both agents; if the concomitant serotonergic agent is withdrawn, discontinuation symptoms can occur.
Peripheral and optic neuropathy
Peripheral neuropathy, as well as optic neuropathy and optic neuritis sometimes progressing to loss of vision, have been reported in patients treated with linezolid; these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days.
All patients should be advised to report symptoms of visual impairment, such as changes in visual acuity, changes in colour vision, blurred vision, or visual field defect. In such cases, prompt evaluation is recommended with referral to an ophthalmologist as necessary. If any patients are taking linezolid for longer than the recommended 28 days, their visual function should be regularly monitored.
If peripheral or optic neuropathy occurs, the continued use of linezolid should be weighed against the potential risks.
There may be an increased risk of neuropathies when linezolid is used in patients currently taking or who have recently taken antimycobacterial medications for the treatment of tuberculosis.
Convulsions
Convulsions have been reported to occur in patients when treated with linezolid. In most of these cases, a history of seizures or risk factors for seizures was reported. Patients should be advised to inform their physician if they have a history of seizures.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the doses used for antibacterial therapy, it does not exert an antidepressive effect. There are very limited data from drug interaction studies and on the safety of linezolid when administered to patients with underlying conditions and/or on concomitant medications which might put them at risk from MAO inhibition. Therefore, linezolid is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible (see sections “Contraindications” and “Interaction with other medicinal products and other types of interactions”).
Use with tyramine-rich foods
Patients should be advised against consuming large amounts of tyramine rich foods (see section “Interaction with other medicinal products and other types of interactions”).
Hypoglycaemia
Post-registration reports indicate cases of symptomatic hypoglycaemia when using linezolid, a non-selective MAO inhibitor, in diabetic patients receiving insulin or oral hypoglycaemic agents. Some MAO inhibitors have been associated with hypoglycaemic episodes in diabetic patients receiving insulin or hypoglycaemic agents. Since there is no causal link between linezolid and hypoglycemia, the patients with diabetes should be warned of a potential hypoglycaemic reaction when using linezolid.
In the event of hypoglycaemia, a reduction of insulin or oral hypoglycaemic agent doses or discontinuation of oral hypoglycaemic agent, insulin or linezolid may be required.
Superinfection
The effects of linezolid therapy on normal flora have not been evaluated in clinical trials.
The use of antibiotics may occasionally result in an overgrowth of non-susceptible organisms. For example, approximately 3% of patients receiving the recommended linezolid doses experienced drug-related candidiasis during clinical trials. If superinfection occurs during therapy, appropriate measures should be taken.
Special populations
Linezolid should be used with special caution in patients with severe renal insufficiency and only when the anticipated benefit is considered to outweigh the theoretical risk (see sections “Method of administration and dosage”).
It is recommended that linezolid should be given to patients with severe hepatic insufficiency only when the perceived benefit outweighs the theoretical risk (see sections “Method of administration and dosage”).
No need to adjust the dose depending on the patient's gender.
Impairment of fertility
Linezolid reversibly decreased fertility and induced abnormal sperm morphology in adult male rats at exposure levels approximately equal to those expected in humans; possible effects of linezolid on the human male reproductive system are not known.
Clinical trials
The safety and effectiveness of linezolid when administered for periods longer than 28 days have not been established.
Controlled clinical trials did not include patients with diabetic foot lesions, decubitus or ischaemic lesions, severe burns or gangrene. Therefore, experience in the use of linezolid in the treatment of these conditions is limited.
Excipients
Each ml of the solution contains 50 mg (i.e. 15 g/300 ml) glucose. This should be taken into account in patients with diabetes mellitus or other conditions associated with glucose intolerance. Each ml of solution also contains 0.48 mg (114 mg/300 ml) sodium. The sodium content should be taken into account in patients on a controlled sodium diet.

Interaction with other medicinal products and other forms of interaction.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). There are very limited data from drug interaction studies and on the safety of linezolid when administered to patients on concomitant medications that might put them at risk from MAO inhibition. Therefore, linezolid is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible (see sections “Contraindications” and “Special precautions”).
Potential interactions producing elevation of blood pressure
In normotensive healthy volunteers, linezolid enhanced the increases in blood pressure caused by pseudoephedrine and phenylpropanolamine hydrochloride. Co-administration of linezolid with either pseudoephedrine or phenylpropanolamine resulted in mean increases in systolic blood pressure of the order of 30-40 mmHg, compared with 11-15 mmHg increases with linezolid alone, 14-18 mmHg with either pseudoephedrine or phenylpropanolamine alone and 8-11 mmHg with placebo. Similar studies in hypertensive subjects have not been conducted. It is recommended that doses of drugs with a vasopressive action, including dopaminergic agents, should be carefully titrated to achieve the desired response when co-administered with linezolid.
Potential serotonergic interactions
The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers. Subjects were administered dextromethorphan (two 20 mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis and hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers. Subjects were administered dextromethorphan (two 20 mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis and hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
There has been one report of a patient experiencing serotonin syndromelike effects while taking linezolid and dextromethorphan which resolved on discontinuation of both medications.
During clinical use of linezolid with serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), cases of serotonin syndrome have been reported. Therefore, while co-administration is contraindicated (see section “Contraindications”), management of patients for whom treatment with linezolid and serotonergic agents is essential, is described in section “Precautions for use”.
Use with tyramine-rich foods
No significant pressor response was observed in subjects receiving both linezolid and less than 100 mg tyramine. This suggests that it is only necessary to avoid ingesting excessive amounts of food and beverages with a high tyramine content (e.g. mature cheese, yeast extracts, undistilled alcoholic beverages and fermented soya bean products such as soy sauce).
Drugs metabolised by cytochrome P450
Linezolid is not detectably metabolised by the cytochrome P450 (CYP) enzyme system and it does not inhibit any of the clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Similarly, linezolid does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug interactions are expected with linezolid.
Rifampicin. The co-administration of rifampicin and linezolid decreased the linezolid Cmax and AUC by 21% and 32%, respectively. The mechanism of this interaction and its clinical significance are unknown.
Warfarin. When warfarin was added to linezolid therapy at steady-state, there was a 10% reduction in mean maximum INR on co-administration with a 5% reduction in AUC INR. There are insufficient data from patients who have received warfarin and linezolid to assess the clinical significance, if any, of these findings.
Antibiotics
Aztreonam. The pharmacokinetics of linezolid or aztreonam is not changed with the concomitant use of these drugs.
Gentamicin. The pharmacokinetics of linezolid or gentamicin is not changed with the concomitant use of these drugs.
In vitro studies have shown additivity or indifference between linezolid and vancomycin, gentamicin, rifampin, imipenem-cilastatin, aztreonam, ampicillin, streptomycin.
Antioxidants
When using the drug with vitamin C or vitamin E, it is not recommended to adjust the dose of linezolid.
Pregnancy and lactation.
Pregnancy. There are limited data from the use of linezolid in pregnant women. Studies in animals have shown reproductive toxicity. A potential risk for humans exists. Linessa should not be used during pregnancy other than the cases when the potential benefit outweighs the theoretical risk.
Breastfeeding. Animal data suggest that linezolid and its metabolites may pass into breast milk. Breastfeeding should be discontinued prior to and throughout administration.
Effects on ability to drive and use machines.
Patients should be warned about the potential for dizziness or symptoms of visual impairment (see sections “Precautions for use” and “Adverse reactions”) whilst receiving linezolid and should be advised not to drive or operate machinery if any of these symptoms occurs.

Method of administration and dosage.
The duration of treatment is dependent on the pathogen, the site of infection and its severity, and on the patient's clinical response.
The following recommendations for duration of therapy reflect those used in the clinical trials. Shorter treatment regimens may be suitable for some types of infection but have not been evaluated in clinical trials.
The maximum treatment duration is 28 days. The safety and effectiveness of linezolid when administered for periods longer than 28 days have not been established.
No increase in the recommended dosage or duration of treatment is required for infections associated with concurrent bacteraemia.
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 linezolid has an oral bioavailability of approximately 100%.
The dose recommendations as per the indications are given in the table below.

^† Newborns <7 days. Most preterm infants <7 days of age (<34 weeks gestation) have lower linezolid systemic clearance and higher AUC than most full-term infants and children under 1 year of age. Treatment of such infants should be started at a dose of 10 mg / kg every 12 hours. For infants with poor clinical response to the drug, a dose of 10 mg / kg every 8 hours may be considered. All patients under 7 days of age should receive a dose of 10 mg / kg every 8 hours.
^‡ The drug is used in another dosage form with the possibility of appropriate dosage.
Special precautions for handling. Do not use if the vial leaks or its content is opaque Any unused medicinal product or waste material should be disposed.
The intravenous infusion is carried out within 30-120 minutes. Do not use the infusion bags in series connections! No other drugs should be added to this solution.
Upon the co-administration of Linessa for intravenous injection and another drug, each of them should be administered separately, according to the recommended dose and route of administration of each drug.
When using one intravenous system for sequentially administration of multiple drugs, this system should be washed with infusion solution compatible with Linessa and another drug injected through the system before and after the administration of the intravenous injection drug.
Compatible solutions for infusion: 0.9% sodium chloride intravenous infusion, 5% glucose intravenous infusion, Ringer-lactate solution for injection.
Incompatibilities
Physical incompatibility occurred when linezolid for intravenous injection was administered via Y-shaped connector along with the following drugs: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium and sulphamethoxazole/trimethoprim. Additionally, linezolid for intravenous injection is chemically incompatible with sodium ceftriaxone.
Elderly: No dose adjustment is required.
Renal impairment. No dose adjustment is required. As approximately 30% of the dose is eliminated during 3-hour haemodialysis initiated 3 hours after drug administration, linezolid should be given after dialysis in patients receiving such treatment (see sections “Pharmacological properties” and “Pharmacokinetics”).
Hepatic impairment. No dose adjustment is required (see sections “Pharmacological properties” and “Pharmacokinetics”).
Children.
Apply from the first days of life.
In children 1 week to 12 years old, administration of 10 mg/kg every 8 hours daily gave exposure approximating to that achieved with 600 mg twice daily in adults.
In neonates up to 1 week of age, the systemic clearance of linezolid (based on kg body weight) increases rapidly in the first week of life. Therefore, neonates given 10 mg/kg every 8 hours daily will have the greatest systemic exposure on the first day after delivery. However, excessive accumulation is not expected with this dosage regimen during the first week of life as clearance increases rapidly over that period. (see section “Method of administration and dosage”).
In 12 to 17 years old adolescents, linezolid pharmacokinetics were similar to that in adults following a 600 mg dose. Therefore, adolescents administered 600 mg every 12 hours daily will have similar exposure to that observed in adults receiving the same dosage.

Overdose.
No specific antidote is known.
No cases of overdose have been reported.
Supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a linezolid dose is removed during 3 hours of haemodialysis, but no data are available for the removal of linezolid by peritoneal dialysis or haemoperfusion. The two primary metabolites of linezolid are also removed to some extent by haemodialysis.

Adverse reactions.
Those most commonly reported were diarrhoea (8.4%), headache (6.5%), nausea (6.3%) and vomiting (4.0%). The most commonly reported drug-related adverse events which led to discontinuation of treatment were headache, diarrhoea, nausea and vomiting. About 3% of patients discontinued treatment because they experienced a drug-related adverse event.
Adverse reactions are listed in the following frequency classification below: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known – cannot be estimated from the available data
Infections and infestations: common – candidiasis, oral candidiasis, vaginal candidiasis, fungal infections; uncommon – vaginitis; rare – antibiotic associated colitis, including pseudomembranous colitis*.
Blood and the lymphatic system disorders: common – anaemia*^†; uncommon – leucopenia*, neutropenia, thrombocytopenia*, eosinophilia; rare – pancytopenia*; not known – myelosuppression*, sideroblastic anaemia*.
Immune system disorders: not known – anaphylaxis.
Metabolism and nutrition disorders: uncommon – hyponatraemia; not known – lactic acidosis*.
Psychiatric disorders: common – insomnia.
Nervous system disorders: common – headache, taste perversion (metallic taste), dizziness; uncommon – convulsions*, hypoaesthesia, paraesthesia; not known – serotonin syndrome**, peripheral neuropathy*.
Eye disorders: uncommon – blurred vision*; rare – changes in visual field defect*; not known – optic neuropathy*, optic neuritis*, loss of vision*, changes in visual acuity*, changes in colour vision*.
Ear and labyrinth disorders: uncommon – tinnitus.
Cardiac disorders: uncommon – arrhythmia (tachycardia).
Vascular disorders: common – hypertension; uncommon – transient ischaemic attacks, phlebitis, thrombophlebitis.
Gastrointestinal disorders: common – diarrhoea, nausea, vomiting, localised or general abdominal pain, constipation, dyspepsia; uncommon – pancreatitis, gastritis, dry mouth, glossitis, loose stools, stomatitis, tongue discolouration or disorder; rare – superficial tooth discolouration.
Hepatobiliary disorders: common – abnormal liver function test; increased AST, ALT or alkaline phosphatase; uncommon – increased total bilirubin.
Skin and subcutaneous tissue disorders: common – pruritus, rash; uncommon – urticaria, dermatitis, diaphoresis; not known – bullous disorders such as those described as Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, alopecia.
Renal and urinary disorders: common – increased BUN; uncommon – renal failure, polyuria, increased creatinine.
Reproductive system and breast disorders: uncommon – vulvovaginal disorder.
General disorders and administration site conditions: common – fever, localized pain; uncommon – chills, fatigue, injection site pain, increased thirst.
Investigations. Chemistry: common – increased LDH, creatine kinase, lipase, amylase or non fasting glucose, decreased total protein, albumin, sodium or calcium. Increased or decreased potassium or bicarbonate.; uncommon – increased sodium or calcium, decreased non fasting glucose. Increased or decreased chloride. Haematology: common – increased neutrophils or eosinophils, decreased haemoglobin, haematocrit or red blood cell count, increased or decreased platelet or white blood cell counts; uncommon – increased reticulocyte count, decreased neutrophils.
* See section “Precautions for use”.
** See sections “Contraindications” and "Interaction with other medicinal products and other types of interactions".
^† In controlled clinical trials where linezolid was administered for up to 28 days, less than 0.1% of the patients reported anaemia. In a compassionate use program of patients with life-threatening infections and underlying co-morbidities, the percentage of patients who developed anaemia when receiving linezolid for ≤ 28 days was 2.5% (33/1326) as compared with 12.3% (53/430) when treated for >28 days. The proportion of cases reporting drug-related serious anaemia and requiring blood transfusion was 9% (3/33) in patients treated for ≤ 28 days and 15% (8/53) in those treated for >28 days.
The adverse reactions to linezolid were considered to be serious in rare cases: localised abdominal pain, transient ischaemic attacks and hypertension.

Shelf life. 2 years.

Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °С.
Keep out of reach of children.
Any unused medicinal product must be disposed.

Packaging.
300 ml in a container. 1 container in PVC film in a carton

Terms of dispensing. On prescription.

Manufacturer. Eurolife Healthcare Pvt. Ltd.

Manufacturer’s registered address. Khasra No. 520, Bhagwanpur, Roorkee, Haridwar, India.

Applicant. Ananta Medicare Ltd.

Applicant’s registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

Date of last update. 17.01.2020