1. Name of the medicinal product

Linezolid solution for infusion USP 600mg/300ml (2mg/ml) Taj Pharma

  1. Qualitative and quantitative composition

Linezolid solution for infusion USP 600mg/300ml (2mg/ml) Taj Pharma
Each ml contains:
Linezolid 2mg
Dextrose USP 50.24mg
Sodium citrate USP 1.64mg
Citric Acid USP 0.85mg
Water for Injection Q.S.

Excipient(s) with known effect

Each 1ml of solution for infusion contains 0.38mg sodium.

Each 300ml bag solution for infusion contains 114mg sodium.

Each 1ml of solution for infusion contains 48mg glucose.

Each 300ml bag solution for infusion contains 14.4 g glucose.

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Solution for infusion.

Isotonic, clear, colourless to yellow solution. The pH of the solution is 4.5 – 5.0.
Osmolality is 270 – 330 mosmol/kg

  1. Clinical particulars
  • Therapeutic indications

Nosocomial pneumonia

Community acquired pneumonia

Linezolid Taj Pharma is indicated in adults for the treatment of community acquired pneumonia and nosocomial pneumonia when known or suspected to be caused by susceptible Gram positive bacteria. In determining whether Linezolid Taj Pharma is an appropriate treatment, the results of microbiological tests or information on the prevalence of resistance to antibacterial agents among Gram positive bacteria should be taken into consideration. (See section 5.1 for the appropriate organisms).

Linezolid Taj Pharma is not active against infections caused by Gram negative pathogens. Specific therapy against Gram negative organisms must be initiated concomitantly if a Gram negative pathogen is documented or suspected.

Complicated skin and soft tissue infections (see section 4.4)

Linezolid Taj Pharma is indicated in adults for the treatment of complicated skin and soft tissue infections only when microbiological testing has established that the infection is known to be caused by susceptible Gram positive bacteria.

Linezolid Taj Pharma is not active against infections caused by Gram negative pathogens. Linezolid Taj Pharma should only be used in patients with complicated skin and soft tissue infections with known or possible coinfection with Gram negative organisms if there are no alternative treatment options available (see section 4.4). In these circumstances treatment against Gram negative organisms must be initiated concomitantly.

Linezolid Taj Pharma should only be initiated in a hospital environment and after consultation with a relevant specialist such as a microbiologist or infectious diseases specialist.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

  • Posology and method of administration

Posology

Linezolid Taj Pharma solution for infusion, film-coated tablets or oral suspension may be used as initial therapy.

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 Taj Pharma has an oral bioavailability of approximately 100%.

Recommended dosage and duration of treatment for adults:

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 Taj Pharma when administered for periods longer than 28 days have not been established. (see section 4.4).

No increase in the recommended dosage or duration of treatment is required for infections associated with concurrent bacteraemia.

The dose recommendation for the solution for infusion and the tablets/granules for oral suspension are identical and are as follows:

InfectionsDosageDuration of treatment
Nosocomial pneumonia600mg twice daily10-14 Consecutive days
Community acquired pneumonia
Complicated skin and soft tissue infections600mg twice daily

Paediatric population: The safety and efficacy of Linezolid Taj Pharma in children aged (< 18 years old) has not been established. Current available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

Elderly: No dose adjustment is required.

Renal impairment: No dose adjustment is required (see sections 4.4 and 5.2).

Severe renal impairment (i.e. CLCR < 30ml/min): No dose adjustment is required. Due to the unknown clinical significance of higher exposure (up to 10 fold) to the two primary metabolites of Linezolid Taj Pharma in patients with severe renal insufficiency, Linezolid Taj Pharma should be used with special caution in these patients and only when the anticipated benefit is considered to outweigh the theoretical risk.

As approximately 30% of a Linezolid Taj Pharma dose is removed during 3 hours of haemodialysis, Linezolid Taj Pharma should be given after dialysis in patients receiving such treatment. The primary metabolites of Linezolid Taj Pharma are removed to some extent by haemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency.

Therefore, Linezolid Taj Pharma should be used with special caution in patients with severe renal insufficiency who are undergoing dialysis and only when the anticipated benefit is considered to outweigh the theoretical risk.

To date, there is no experience of Linezolid Taj Pharma administration to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than haemodialysis).

Hepatic impairment: No dose adjustment is required. However, there are limited clinical data and it is recommended that Linezolid Taj Pharma should be used in such patients only when the anticipated benefit is considered to outweigh the theoretical risk (see sections 4.4 and 5.2).

Method of administration

The recommended Linezolid Taj Pharma dosage should be administered intravenously twice daily.

Route of administration: Intravenous use.

The solution for infusion should be administered over a period of 30 to 120 minutes.

  • Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Linezolid Taj Pharma 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, Linezolid Taj Pharma 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.
  • Patients taking any of the following medications: serotonin re-uptake inhibitors (see section 4.4), tricyclic antidepressants, serotonin 5-HT1receptor 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.

Animal data suggest that Linezolid Taj Pharma and its metabolites may pass into breast milk and, accordingly, breastfeeding should be discontinued prior to and throughout administration (see section 4.6).

  • Special warnings and precautions for use

Myelosuppression

Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving Linezolid Taj Pharma. In cases where the outcome is known, when Linezolid Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma regardless of baseline blood count.

In compassionate use studies, a higher incidence of serious anaemia was reported in patients receiving Linezolid Taj Pharma 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 Taj Pharma 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 Taj Pharma therapy for more than 28 days. Most patients fully or partially recovered following discontinuation of Linezolid Taj Pharma 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 Taj Pharma, 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 4.1). 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 Taj Pharma 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 Taj Pharma. If antibiotic-associated diarrhoea or antibioticassociated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including Linezolid Taj Pharma, 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 Taj Pharma. 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 Taj Pharma should receive immediate medical attention. If lactic acidosis occurs, the benefits of continued use of Linezolid Taj Pharma should be weighed against the potential risks.

Mitochondrial dysfunction

Linezolid Taj Pharma 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.

Serotonin syndrome

Spontaneous reports of serotonin syndrome associated with the co-administration of Linezolid Taj Pharma and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been reported. Co-administration of Linezolid Taj Pharma and serotonergic agents is therefore contraindicated (see section 4.3) except where administration of Linezolid Taj Pharma 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 Taj Pharma; 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 Taj Pharma 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 Taj Pharma should be weighed against the potential risks.

There may be an increased risk of neuropathies when Linezolid Taj Pharma 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 Taj Pharma. 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 Taj Pharma 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 Taj Pharma when administered to patients with underlying conditions and/or on concomitant medications which might put them at risk from MAO inhibition. Therefore, Linezolid Taj Pharma is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible (see sections 4.3 and 4.5).

Use with tyramine-rich foods

Patients should be advised against consuming large amounts of tyramine rich foods (see section 4.5).

Superinfection

The effects of Linezolid Taj Pharma 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 Taj Pharma doses experienced drug-related candidiasis during clinical trials. Should superinfection occur during therapy, appropriate measures should be taken.

Special populations

Linezolid Taj Pharma 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 4.2 and 5.2).

It is recommended that Linezolid Taj Pharma should be given to patients with severe hepatic insufficiency only when the perceived benefit outweighs the theoretical risk (see sections 4.2 and 5.2).

Impairment of fertility

Linezolid Taj Pharma 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 Taj Pharma on the human male reproductive system are not known (see section 5.3).

Clinical trials

The safety and effectiveness of Linezolid Taj Pharma 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 Taj Pharma in the treatment of these conditions is limited.

Excipients

Eachml of the solution contains 48mg (i.e. 14.4 g/300ml) glucose. This should be taken into account in patients with diabetes mellitus or other conditions associated with glucose intolerance. Eachml of solution also contains 0.38mg (114mg/300ml) 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 Taj Pharma 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 Taj Pharma when administered to patients on concomitant medications that might put them at risk from MAO inhibition. Therefore, Linezolid Taj Pharma is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible (see sections 4.3 and 4.4).

Potential interactions producing elevation of blood pressure

In normotensive healthy volunteers, Linezolid Taj Pharma enhanced the increases in blood pressure caused by pseudoephedrine and phenylpropanolamine hydrochloride. Co-administration of Linezolid Taj Pharma 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 Taj Pharma 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 Taj Pharma.

Potential serotonergic interactions

The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers. Subjects were administered dextromethorphan (two 20mg doses given 4 hours apart) with or without Linezolid Taj Pharma. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis and hyperpyrexia) have been observed in normal subjects receiving Linezolid Taj Pharma and dextromethorphan.

Post marketing experience: there has been one report of a patient experiencing serotonin syndromelike effects while taking Linezolid Taj Pharma and dextromethorphan which resolved on discontinuation of both medications.

During clinical use of Linezolid Taj Pharma 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 4.3), management of patients for whom treatment with Linezolid Taj Pharma and serotonergic agents is essential, is described in section 4.4.

Use with tyramine-rich foods

No significant pressor response was observed in subjects receiving both Linezolid Taj Pharma and less than 100mg 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 Taj Pharma 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 Taj Pharma does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug interactions are expected with Linezolid Taj Pharma.

Rifampicin

The effect of rifampicin on the pharmacokinetics of Linezolid Taj Pharma was studied in sixteen healthy adult male volunteers administered Linezolid Taj Pharma 600mg twice daily for 2.5 days with and without rifampicin 600mg once daily for 8 days. Rifampicin decreased the Linezolid Taj Pharma Cmax and AUC by a mean 21% [90% CI, 15, 27] and a mean 32% [90% CI, 27, 37], respectively. The mechanism of this interaction and its clinical significance are unknown.

Warfarin

When warfarin was added to Linezolid Taj Pharma 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 Taj Pharma to assess the clinical significance, if any, of these findings.

  • Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of Linezolid Taj Pharma in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). A potential risk for humans exists.

Linezolid Taj Pharma should not be used during pregnancy unless clearly necessary i.e. only if the potential benefit outweighs the theoretical risk.

Breast-feeding

Animal data suggest that Linezolid Taj Pharma and its metabolites may pass into breast milk and, accordingly, breastfeeding should be discontinued prior to and throughout administration.

Fertility

In animal studies, Linezolid Taj Pharma caused a reduction in fertility (see section 5.3).

  • Effects on ability to drive and use machines

Patients should be warned about the potential for dizziness or symptoms of visual impairment (as described in section 4.4 and 4.8) whilst receiving Linezolid Taj Pharma and should be advised not to drive or operate machinery if any of these symptoms occurs.

  • Undesirable effects

The table below provides a listing of adverse drug reactions with frequency based on all-causality data from clinical studies that enrolled more than 2,000 adult patients who received the recommended Linezolid Taj Pharma doses for up to 28 days.

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.

Additional adverse reactions reported from post-marketing experience are included in the table with frequency category ‘Not known’, since the actual frequency cannot be estimated from the available data.

The following undesirable effects have been observed and reported during treatment with Linezolid Taj Pharma with the following frequencies: 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)

System Organ ClassCommon

(≥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)Frequency not known (cannot be estimated from available data)
Infections and infestationsCandidiasis, oral candidiasis, vaginal candidiasis, fungal infectionsVaginitisAntibiotic associated colitis, including pseudomembranous colitis*
Blood and the lymphatic system disordersAnaemia*†Leucopenia*, neutropenia, thrombocytopenia*, eosinophiliaPancytopenia*Myelosuppression*, sideroblastic anaemia*
Immune system disordersAnaphylaxis
Metabolism and nutrition disordersHyponatraemiaLactic acidosis*
Psychiatric disordersInsomnia
Nervous system disordersHeadache, taste perversion (metallic taste), DizzinessConvulsions*, hypoaesthesia, paraesthesiaSerotonin syndrome**, peripheral neuropathy*
Eye disordersBlurred vision*Changes in visual field defect*Optic neuropathy*, optic neuritis*, loss of vision*, changes in visual acuity*, changes in colour vision*
Ear and labyrinth disordersTinnitus
Cardiac disordersArrhythmia (tachycardia)
Vascular disordersHypertensionTransient ischaemic attacks, phlebitis, thrombophlebitis
Gastrointestinal disordersDiarrhoea, nausea, vomiting, localised or general abdominal pain, constipation, dyspepsiaPancreatitis, gastritis, dry mouth, glossitis, loose stools, stomatitis, tongue discolouration or disorderSuperficial tooth discolouration
Hepatobiliary disordersAbnormal liver function test; increased AST, ALT or alkaline phosphataseIncreased total bilirubin
Skin and subcutaneous tissue disordersPruritus, rashUrticaria, dermatitis, diaphoresisBullous disorders such as those described as Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, alopecia
Renal and urinary disordersIncreased BUNRenal failure, polyuria, increased creatinine
Reproductive system and breast disordersVulvovaginal disorder
General disorders and administration site conditionsFever, localized painChills, fatigue, injection site pain, increased thirst
InvestigationsChemistry Increased LDH, creatine kinase, lipase, amylase or non fasting glucose. Decreased total protein, albumin, sodium or calcium. Increased or decreased potassium or bicarbonate.

Haematology Increased neutrophils or eosinophils. Decreased haemoglobin, haematocrit or red blood cell count. Increased or decreased platelet or white blood cell counts.

Chemistry Increased sodium or calcium. Decreased non fasting glucose. Increased or decreased chloride.

Haematology Increased reticulocyte count. Decreased neutrophils.

* See section 4.4.

** See sections 4.3 and 4.5

† See below

The following adverse reactions to Linezolid Taj Pharma were considered to be serious in rare cases: localised abdominal pain, transient ischaemic attacks and hypertension.

†In controlled clinical trials where Linezolid Taj Pharma 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 Taj Pharma 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.

Paediatric population

Safety data from clinical studies based on more than 500 paediatric patients (from birth to 17 years) do not indicate that the safety profile of Linezolid Taj Pharma for paediatric patients differs from that for adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

  • Overdose

No specific antidote is known.

No cases of overdose have been reported. However, the following information may prove useful:

Supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid Taj Pharma dose is removed during 3 hours of haemodialysis, but no data are available for the removal of Linezolid Taj Pharma by peritoneal dialysis or haemoperfusion. The two primary metabolites of Linezolid Taj Pharma are also removed to some extent by haemodialysis.

Signs of toxicity in rats following doses of 3000mg/kg/day Linezolid Taj Pharma were decreased activity and ataxia whilst dogs treated with 2000mg/kg/day experienced vomiting and tremors.

  1. Pharmacological properties
    • Pharmacodynamic properties

Pharmacotherapeutic group: Other antibacterials.

General Properties

Linezolid Taj Pharma 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 Taj Pharma 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 in vitro postantibiotic effect (PAE) of Linezolid Taj Pharma for Staphylococcus aureus was approximately 2 hours. When measured in animal models, the in vivo PAE was 3.6 and 3.9 hours for Staphylococcus aureus and Streptococcus pneumoniae, respectively. In animal studies, the key pharmacodynamic parameter for efficacy was the time for which the Linezolid Taj Pharma plasma level exceeded the minimum inhibitory concentration (MIC) for the infecting organism.

Breakpoints

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for staphylococci and enterococci are Susceptible ≤ 4mg/L and Resistant >4mg/L. For streptococci (including S. pneumoniae) the breakpoints are Susceptible ≤ 2mg/L and Resistant >4mg/L.

Non-species related MIC breakpoints are susceptible ≤ 2mg/L and Resistant > 4mg/L. Nonspecies related breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for organisms that have not been given a specific breakpoint and not for those species where susceptibility testing is not recommended.

Susceptibility

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.

Category
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 influenzae

Moraxella catarrhalis

Neisseria species

Enterobacteriaceae

Pseudomonas species

*Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications

Whereas Linezolid Taj Pharma shows some in vitro activity against Legionella, Chlamydia pneumoniae and Mycoplasma pneumoniae, there are insufficient data to demonstrate clinical efficacy.

Resistance

Cross resistance

Linezolid Taj Pharma’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 Taj Pharma is usually active against organisms which are resistant to one or more other classes of antimicrobial agents.

Resistance to Linezolid Taj Pharma is associated with point mutations in the 23S rRNA.

As documented with other antibiotics when used in patients with difficult to treat infections and/or for prolonged periods, emergent decreases in susceptibility have been observed with Linezolid Taj Pharma. Resistance to Linezolid Taj Pharma has been reported in enterococci, Staphylococcus aureus and coagulase negative staphylococci. This generally has been associated with prolonged courses of therapy and the presence of prosthetic materials or undrained abscesses. When antibiotic-resistant organisms are encountered in the hospital it is important to emphasize infection control policies.

Information from clinical trials

Studies in the paediatric population

In an open study, the efficacy of Linezolid Taj Pharma (10mg/kg q8h) was compared to vancomycin (10-15mg/kg q6-24h) in treating infections due to suspected or proven resistant Gram-positive pathogens (including nosocomial pneumonia, complicated skin and skin structure infections, catheter-related bacteraemia, bacteraemia of unknown source, and other infections), in children from birth to 11 years. Clinical cure rates in the clinically evaluable population were 89.3% (134/150) and 84.5% (60/71) for Linezolid Taj Pharma and vancomycin, respectively (95%CI: -4.9, 14.6).

  • Pharmacokinetic properties

Linezolid Taj Pharma primarily contains (s)-Linezolid Taj Pharma which is biologically active and is metabolised to form inactive derivatives.

Absorption

Linezolid Taj Pharma is rapidly and extensively absorbed following oral dosing. Maximum plasma concentrations are reached within 2 hours of dosing. Absolute oral bioavailability of Linezolid Taj Pharma (oral and intravenous dosing in a crossover study) is complete (approximately 100%). Absorption is not significantly affected by food and absorption from the oral suspension is similar to that achieved with the film-coated tablets.

Plasma Linezolid Taj Pharma Cmax and Cmin (mean and [SD]) at steady-state following twice daily intravenous dosing of 600mg have been determined to be 15.1 [2.5]mg/l and 3.68 [2.68]mg/l, respectively.

In another study following oral dosing of 600mg twice daily to steady-state, Cmax and Cmin were determined to be 21.2 [5.8]mg/l and 6.15 [2.94]mg/l, respectively. Steady-state conditions are achieved by the second day of dosing.

Distribution

Volume of distribution at steady-state averages at about 40-50 litres in healthy adults and approximates to total body water. Plasma protein binding is about 31% and is not concentration dependent.

Linezolid Taj Pharma concentrations have been determined in various fluids from a limited number of subjects in volunteer studies following multiple dosing. The ratio of Linezolid Taj Pharma in saliva and sweat relative to plasma was 1.2:1.0 and 0.55:1.0, respectively. The ratio for epithelial lining fluid and alveolar cells of the lung was 4.5:1.0 and 0.15:1.0, when measured at steady-state Cmax, respectively. In a small study of subjects with ventricular-peritoneal shunts and essentially non-inflamed meninges, the ratio of Linezolid Taj Pharma in cerebrospinal fluid to plasma at Cmax was 0.7:1.0 after multiple Linezolid Taj Pharma dosing.

Biotransformation

Linezolid Taj Pharma 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 (PNU-142300) and the hydroxyethyl glycine metabolite (PNU-142586). The hydroxyethyl glycine metabolite (PNU-142586) is the predominant human metabolite and is believed to be formed by a non-enzymatic process. The aminoethoxyacetic acid metabolite (PNU142300) is less abundant. Other minor, inactive metabolites have been characterised.

Elimination

In patients with normal renal function or mild to moderate renal insufficiency, Linezolid Taj Pharma is primarily excreted under steady-state conditions in the urine as PNU-142586 (40%), parent drug (30%) and PNU-142300 (10%). Virtually no parent drug is found in the faeces whilst approximately 6% and 3% of each dose appears as PNU-142586 and PNU-142300, respectively. The elimination half-life of Linezolid Taj Pharma averages at about 5-7 hours.

Non-renal clearance accounts for approximately 65% of the total clearance of Linezolid Taj Pharma. A small degree of non-linearity in clearance is observed with increasing doses of Linezolid Taj Pharma. This appears to be due to lower renal and nonrenal clearance at higher Linezolid Taj Pharma concentrations. However, the difference in clearance is small and is not reflected in the apparent elimination half-life.

Special Populations

Renal impairment: After single doses of 600mg, there was a 7-8 fold increase in exposure to the two primary metabolites of Linezolid Taj Pharma in the plasma of patients with severe renal insufficiency (i.e. creatinine clearance <30ml/min). However, there was no increase in AUC of parent drug. Although there is some removal of the major metabolites of Linezolid Taj Pharma by haemodialysis, metabolite plasma levels after single 600mg doses were still considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency.

In 24 patients with severe renal insufficiency, 21 of whom were on regular haemodialysis, peak plasma concentrations of the two major metabolites after several days dosing were about 10 fold those seen in patients with normal renal function. Peak plasma levels of Linezolid Taj Pharma were not affected.

The clinical significance of these observations has not been established as limited safety data are currently available (see sections 4.2 and 4.4).

Hepatic impairment: Limited data indicate that the pharmacokinetics of Linezolid Taj Pharma, PNU-142300 and PNU-142586 are not altered in patients with mild to moderate hepatic insufficiency (i.e. Child-Pugh class A or B). The pharmacokinetics of Linezolid Taj Pharma in patients with severe hepatic insufficiency (i.e. Child-Pugh class C) have not been evaluated. However, as Linezolid Taj Pharma is metabolised by a non-enzymatic process, impairment of hepatic function would not be expected to significantly alter its metabolism (see sections 4.2 and 4.4).

Paediatric population (< 18 years old): There are insufficient data on the safety and efficacy of Linezolid Taj Pharma in children and adolescents (< 18 years old) and therefore, use of Linezolid Taj Pharma in this age group is not recommended (see section 4.2). Further studies are needed to establish safe and effective dosage recommendations. Pharmacokinetic studies indicate that after single and multiple doses in children (1 week to 12 years), Linezolid Taj Pharma clearance (based on kg body weight) was greater in paediatric patients than in adults, but decreased with increasing age.

In children 1 week to 12 years old, administration of 10mg/kg every 8 hours daily gave exposure approximating to that achieved with 600mg twice daily in adults.

In neonates up to 1 week of age, the systemic clearance of Linezolid Taj Pharma (based on kg body weight) increases rapidly in the first week of life. Therefore, neonates given 10mg/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.

In adolescents (12 to 17 years old), Linezolid Taj Pharma pharmacokinetics were similar to that in adults following a 600mg dose. Therefore, adolescents administered 600mg every 12 hours daily will have similar exposure to that observed in adults receiving the same dosage.

In paediatric patients with ventriculoperitoneal shunts who were administered Linezolid Taj Pharma 10mg/kg either 12 hourly or 8 hourly, variable cerebrospinal fluid (CSF) Linezolid Taj Pharma concentrations were observed following either single or multiple dosing of Linezolid Taj Pharma. Therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of Linezolid Taj Pharma for the empirical treatment of paediatric patients with central nervous system infections is not recommended.

Elderly: The pharmacokinetics of Linezolid Taj Pharma are not significantly altered in elderly patients aged 65 and over.

Female patients: Females have a slightly lower volume of distribution than males and the mean clearance is reduced by approximately 20% when corrected for body weight. Plasma concentrations are higher in females and this can partly be attributed to body weight differences. However, because the mean half life of Linezolid Taj Pharma is not significantly different in males and females, plasma concentrations in females are not expected to substantially rise above those known to be well tolerated and, therefore, dose adjustments are not required.

  • Preclinical safety data

Linezolid Taj Pharma decreased fertility and reproductive performance of male rats at exposure levels approximately equal to those in humans. In sexually mature animals these effects were reversible. However, these effects did not reverse in juvenile animals treated with Linezolid Taj Pharma for nearly the entire period of sexual maturation. Abnormal sperm morphology in testis of adult male rats, and epithelial cell hypertrophy and hyperplasia in the epididymis were noted. Linezolid Taj Pharma appeared to affect the maturation of rat spermatozoa. Supplementation of testosterone had no effect on Linezolid Taj Pharma-mediated fertility effects. Epididymal hypertrophy was not observed in dogs treated for 1 month, although changes in the weights of prostate, testes and epididymis were apparent.

Reproductive toxicity studies in mice and rats showed no evidence of a teratogenic effect at exposure levels 4 times or equivalent, respectively, to those in humans. The same Linezolid Taj Pharma concentrations caused maternal toxicity in mice and were related to increased embryo death including total litter loss, decreased fetal body weight and an exacerbation of the normal genetic predisposition to sternal variations in the strain of mice. In rats, slight maternal toxicity was noted at exposures lower than clinical exposures. Mild fetal toxicity, manifested as decreased fetal body weights, reduced ossification of sternebrae, reduced pup survival and mild maturational delays were noted. When mated, these same pups showed evidence of a reversible dose-related increase in pre-implantation loss with a corresponding decrease in fertility. In rabbits, reduced fetal body weight occurred only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) at low exposure levels 0.06 times compared to the expected human exposure based on AUCs. The species is known to be sensitive to the effects of antibiotics.

Linezolid Taj Pharma and its metabolites are excreted into the milk of lactating rats and the concentrations observed were higher than those in maternal plasma.

Linezolid Taj Pharma produced reversible myelosuppression in rats and dogs.

In rats administered Linezolid Taj Pharma orally for 6 months, non-reversible, minimal to mild axonal degeneration of sciatic nerves was observed at 80mg/kg/day; minimal degeneration of the sciatic nerve was also observed in 1 male at this dose level at a 3-month interim necropsy. Sensitive morphologic evaluation of perfusion-fixed tissues was conducted to investigate evidence of optic nerve degeneration. Minimal to moderate optic nerve degeneration was evident in 2 of 3 male rats after 6 months of dosing, but the direct relationship to drug was equivocal because of the acute nature of the finding and its asymmetrical distribution. The optic nerve degeneration observed was microscopically comparable to spontaneous unilateral optic nerve degeneration reported in aging rats and may be an exacerbation of common background change.

Preclinical data, based on conventional studies of repeated-dose toxicity and genotoxicity, revealed no special hazard for humans beyond those addressed in other sections of this Summary of Product Characteristics. Carcinogenicity / oncogenicity studies have not been conducted in view of the short duration of dosing and lack of genotoxicity.

  1. Pharmaceutical particulars
  • List of excipients

Glucose monohydrate

Sodium citrate

Citric acid anhydrous

Hydrochloric acid (as 10% solution; for pH-adjustment)

Sodium hydroxide (as 10% solution; for pH adjustment) Water for injections

  • Incompatibilities

Additives should not be introduced into this solution. If Linezolid Taj Pharma is to be given concomitantly with other drugs, each drug should be given separately in accordance with its own directions for use. Similarly, if the same intravenous line is to be used for sequential infusion of several drugs, the line should be flushed prior to and following Linezolid Taj Pharma administration with a compatible infusion solution (see section 6.6).

Linezolid Taj Pharma solution for infusion is known to be physically incompatible with the following compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium and sulphamethoxazole / trimethoprim. Additionally, it is chemically incompatible with ceftriaxone sodium.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

  • Shelf life

Before opening: 30 months

After opening: From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

  • Special precautions for storage

Store in the original package (overwrap and carton) in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

  • Nature and contents of container

A clear colourless or yellowish polypropylene infusion bag with one port or two ports in a transparent foil laminate overwrap bag. The bag holds 300ml solution and is packaged in a box.

Box containing 1*, 2**, 5, 10, 20 or 25 infusion bag(s). Additionally, the following boxes may also be supplied in hospital packs of:

*5, 10 or 20

**3, 6 or 10

Not all package sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only. Remove overwrap only when ready to use, then check for minute leaks by squeezing the bag firmly. If the bag leaks, do not use as sterility may be impaired. The solution should be visually inspected prior to use and only clear solutions, without particles should be used.

Do not use these bags in series connections. Any unused solution must be discarded. Do not reconnect partially used bags.

Linezolid Taj Pharma solution for infusion is compatible with the following solutions: 5% glucose intravenous infusion, 0.9% sodium chloride intravenous infusion, Ringer-lactate solution for injection (Hartmann’s solution for injection).

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Linezolid Taj Pharma solution for infusion USP 600mg/300ml (2mg/ml) Taj Pharma

Package Leaflet: Information for the user

Linezolid Taj Pharma

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Linezolid Taj Pharma is and what it is used for
  2. What you need to know before you use Linezolid Taj Pharma
  3. How to use Linezolid Taj Pharma
  4. Possible side effects
  5. How to store Linezolid Taj Pharma
  6. Contents of the pack and other information

1. What Linezolid Taj Pharma is and what it is used for

Linezolid Taj Pharma is an antibiotic of the oxazolidinones group that works by stopping the growth of certain bacteria (germs) that cause infections. It is used to treat pneumonia and some infections in the skin or under the skin. Your doctor will have decided if Linezolid Taj Pharma is suitable to treat your infection.

  1. What you need to know before you use Linezolid Taj Pharma

Do not use Linezolid Taj Pharma

  • If you are allergic to Linezolid Taj Pharma or any of the other ingredients of this medicine (listed in section 6)
  • If you are taking or have taken within the last 2 weeks any medicines known as monoamine oxidase inhibitors (MAOIs for example phenelzine, isocarboxazid, selegiline, moclobemide).

These medications may be used to treat depression or Parkinson’s disease;

  • If you are breast-feeding. This is because Linezolid Taj Pharma passes into breast milk and could affect the baby.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Linezolid Taj Pharma.

Linezolid Taj Pharma may not be suitable for you if you answer yes to any of the following questions. In this case tell your doctor as he/she will need to check your general health and your blood pressure before and during your treatment or may decide that another treatment is better for you.

Ask your doctor if you are not sure whether these categories apply to you.

  • Do you have high blood pressure, whether or not you are taking medicines for this?
  • Have you been diagnosed with an overactive thyroid?
  • Do you have a tumour of the adrenal glands (phaeochromocytoma) or carcinoid syndrome (caused by tumours of the hormone system with symptoms of diarrhoea, flushing of the skin, wheezing)?
  • Do you suffer from manic depression, schizoaffective disorder, mental confusion or other mental problems?

Take special care with Linezolid Taj Pharma

Tell your doctor before you take this medicine if you:

  • bruise and bleed easily
  • are anaemic (have low red blood cells)
  • are prone to getting infections
  • have a history of seizures
  • have liver problems or kidney problems particularly if you are on dialysis
  • have diarrhoea

Tell your doctor immediately if during treatment you suffer from

  • problems with your vision such as blurred vision, changes in colour vision, difficulty in seeing detail or if your field of vision becomes restricted.
  • loss of sensitivity in your arms or legs or a sensation of tingling or pricking in your arms or legs.
  • you may develop diarrhoea while taking or after taking antibiotics, including Linezolid Taj Pharma. If this becomes severe or persistent or you notice that your stool contains blood or mucus, you should stop taking Linezolid Taj Pharma immediately and consult your doctor. In this situation, you should not take medicines that stop or slow bowel movement.
  • recurrent nausea or vomiting, abdominal pain or rapid breathing

Other medicines and Linezolid Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

There is a risk that Linezolid Taj Pharma may sometimes interact with certain other medicines to cause side effects such as changes in blood pressure, temperature or heart rate.

Tell your doctor if you are taking or have taken within the last 2 weeks the following medicines as Linezolid Taj Pharma must not be taken if you are already taking these medicines or have taken them recently. (See also Section 2 above ‘Do not use Linezolid Taj Pharma’).

  • monoamine oxidase inhibitors (MAOIs for example phenelzine, isocarboxazid, selegiline, moclobemide). These may be used to treat depression or Parkinson’s disease

Also tell your doctor if you are taking the following medicines. Your doctor may still decide to give you Linezolid Taj Pharma, but will need to check your general health and your blood pressure before and during your treatment. In other cases, your doctor may decide that another treatment is better for you.

  • Decongestant cold or flu remedies containing pseudoephedrine or phenylpropanolamine.
  • Some medicines used to treat asthma such as salbutamol, terbutaline, fenoterol.
  • Certain antidepressants known as tricyclics or SSRIs (selective serotonin reuptake inhibitors).

There are many of these, including amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline.

  • Medicines used to treat migraine such as sumatriptan and zolmitriptan.
  • Medicines used to treat sudden, severe allergic reactions such as adrenaline (epinephrine).
  • Medicines which increase your blood pressure, such as noradrenaline (norepinephrine), dopamine and dobutamine
  • Medicines used to treat moderate to severe pain, such as pethidine.
  • Medicines used to treat anxiety disorders, such as buspirone.
  • Medicines that stop blood clotting, such as warfarin.
  • An antibiotic called rifampicin.

Linezolid Taj Pharma with food and drink

  • You can use Linezolid Taj Pharma either before, during or after a meal.
  • Avoid eating large amounts of mature cheese, yeast extracts, or soya bean extracts e.g. soy sauce and drinking alcohol, especially draught beers and wine. This is because this medicine may react with a substance called tyramine which is naturally present in some foods. This interaction may cause an increase in your blood pressure.
  • If you develop a throbbing headache after eating or drinking, tell your doctor or pharmacist immediately.

Pregnancy, breast-feeding and fertility

The effect of Linezolid Taj Pharma in pregnant women is not known. Therefore it should not be used in pregnancy unless advised by your doctor. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

You should not breast-feed when using Linezolid Taj Pharma because it passes into breast milk and could affect the baby.

Driving and using machines

Linezolid Taj Pharma may make you feel dizzy or experience problems with your vision. If this happens, do not drive or operate any machinery. Remember that if you are unwell your ability to drive or operate machinery may be affected.

Linezolid Taj Pharma contains glucose and sodium

Glucose

Each 1ml of Linezolid Taj Pharma solution contains 48mg glucose (14.4 g glucose in one bag).

This should be taken into account in patients with diabetes mellitus.

Sodium

Each 1ml of Linezolid Taj Pharma solution contains 0.38mg sodium (114mg sodium in one bag).

To be taken into consideration by patients on a controlled sodium diet.

  1. How to use Linezolid Taj Pharma

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Adults

This medicine will be given to you through a drip (by infusion into a vein) by a doctor or healthcare professional. The recommended dose for adults (18 years and older) is 300ml (600mg Linezolid Taj Pharma) twice daily which is given directly into the blood stream (intravenously) by a drip over a period of 30 to 120 minutes.

If you are on kidney dialysis, you should be given Linezolid Taj Pharma after your dialysis treatment.

A course of treatment usually lasts 10 to 14 days, but can last up to 28 days. The safety and effectiveness of this medicine have not been established for treatment periods longer than 28 days.

Your doctor will decide how long you should be treated.

While you are using Linezolid Taj Pharma, your doctor should perform regular blood tests to monitor your blood count.

Your doctor should monitor your eyesight if you use Linezolid Taj Pharma for more than 28 days.

Use in children and adolescents

Linezolid Taj Pharma is not normally used to treat children and adolescents (under 18 years old).

If you use more Linezolid Taj Pharma than you should

If you are concerned that you may have been given too much Linezolid Taj Pharma, tell your doctor or a nurse at once.

If you forget to use Linezolid Taj Pharma

As you will be given this medicine under close supervision, it is very unlikely that you will miss a dose. If you think that you have missed a dose of treatment, tell a doctor or nurse at once. Do not take a double dose to make up for a forgotten dose.

  1. Possible side effects

Like all medicines this medicine can cause side-effects, although not everybody gets them.

Tell your doctor, nurse or pharmacist immediately if you notice any of these side effects during your treatment with Linezolid Taj Pharma.

The serious side effects (with frequency in brackets) of Linezolid Taj Pharma are

  • severe skin disorder (not known), swelling, particularly around the face and neck (not known), wheezing and/or difficulty breathing (not known). This may be the sign of an allergic reaction and it may be necessary for you to stop taking Linezolid Taj Pharma. Skin reactions such as red sore skin and flaking (dermatitis) (uncommon), rash (common), itching (common).
  • problems with your vision such as blurred vision (uncommon), changes in colour vision (not known), difficulty in seeing detail (not known) or if your field of vision becomes restricted (rare).
  • severe diarrhoea containing blood and/or mucus (antibiotic associated colitis including pseudomembranous colitis), which in rare circumstances may develop into complications that are life-threatening (rare).
  • recurrent nausea or vomiting, abdominal pain or rapid breathing (not known).
  • fits or seizures (uncommon) have been reported with Linezolid Taj Pharma. You should let your doctor know if you experience agitation, confusion, delirium, rigidity, tremor, incoordination and seizure while also taking antidepressants known as SSRI’s (see section 2) (not known).
  • unexplained bleeding or bruising, which may be due to changes in the numbers of certain cells in the blood which may affect blood clotting or lead to anaemia (common).
  • changes in numbers of certain cells in the blood which may affect your ability to fight infection (common). Some signs of infection include: any fever (common), sore throat (uncommon), mouth ulcers (uncommon) and tiredness (uncommon).
  • inflammation of the pancreas (uncommon).
  • convulsions (uncommon).
  • transient ischaemic attacks (temporary disturbance of blood flow to the brain causing short term symptoms such as loss of vision, leg and arm weakness, slurring of speech and loss of consciousness) (uncommon).
  • “ringing” in the ears (tinnitus) (uncommon).
  • Numbness, tingling or blurred vision have been reported by patients who have been given Linezolid Taj Pharma for more than 28 days. If you experience difficulties with your vision you should consult your doctor as soon as possible.

Other side effects include:

Common (may affect up to 1 in 10 people)

  • Fungal infections especially vaginal or oral “thrush”
  • Headache
  • Metallic taste in the mouth
  • Diarrhoea, nausea or vomiting
  • Changes in some blood test results including those measuring your kidney or liver function or blood sugar levels
  • Difficulty in sleeping
  • Increased blood pressure
  • Anaemia (low red blood cells)
  • Dizziness
  • Localised or general abdominal pain
  • Constipation
  • Indigestion
  • Localised pain

Uncommon (may affect up to 1 in 100 people)

  • Inflammation of the vagina or genital area in women
  • Sensations such as tingling or feeling numb
  • Swollen, sore, or discoloured tongue
  • Pain at and around the place where the infusion (drip) was given
  • Inflammation of the veins (including where the infusion (drip) was given)
  • A need to urinate more often
  • Chills
  • Feeling thirsty
  • Increased sweating
  • Changes in proteins, salts or enzymes in the blood which measure kidney or liver function
  • Hyponatraemia (low blood sodium levels)
  • Kidney failure
  • Reduction in platelets
  • Abdominal bloating
  • Injection site pain
  • Increase in creatinine
  • Stomach pain
  • Changes in heart rate (e.g., increase rate)

Rare (may affect up to 1 in 1000 people)

  • Superficial tooth discolouration, removable with professional dental cleaning (manual descaling)

Not known (frequency cannot be estimated from the available data)

  • Alopecia (hair loss)
  • Decrease of the blood cell count
  • Weakness and/or sensory changes

Reporting of side effects

If you get any side effects, talk to your doctor or, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Linezolid Taj Pharma

As you will be given this medicine under close medical supervision, Hospital Staff will comply with the following advices:

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bag after EXP. The first two digits indicate the month and the last four digits indicate the year. The expiry date refers to the last day of that month. Use the medicine as soon as the seal is broken.

After opening: From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Store in the original package (overwrap and carton) in order to protect from light.

Do not use this medicine if you notice that the solution is not clear and contains particles.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines that you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Linezolid Taj Pharma contains

  • The active substance is Linezolid Taj Pharma. Eachml of solution contains 2mg Linezolid Taj Pharma.
  • The other ingredients are glucose monohydrate (a type of sugar), sodium citrate, citric acid anhydrous, hydrochloric acid; as 10% solution) for pH-adjustment or sodium hydroxide; as 10% solution) for pH-adjustment and water for injections.

What Linezolid Taj Pharma looks like and contents of the pack

Linezolid Taj Pharma is presented as a clear, colourless to yellow solution in single infusion bags containing 300ml (600mg Linezolid Taj Pharma) of solution.

Each box contains 1, 2, 5, 10, 20 or 25 infusion bag(s). Additionally, hospital packaging of 3, 5, 6, 10 or 20 boxes containing either 1 or 2 infusion bag(s) are available.

Not all package sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

<————————————————————————————————————————–>

The following information is intended for healthcare professionals only:

Linezolid Taj Pharma 2mg/ml solution for infusion

Linezolid Taj Pharma

IMPORTANT: Refer to Summary of Product Characteristics before prescribing.

Linezolid Taj Pharma is not active against infections caused by Gram negative pathogens. Specific therapy against Gram negative organisms must be initiated concomitantly if co-infection with a Gram negative pathogen is documented or suspected.

Description

A clear colourless or yellowish polypropylene infusion bag with one port or two ports in a transparent foil laminate overwrap bag. The bag holds 300ml solution and is packaged in a box.

Box containing 1*, 2**, 5, 10, 20 or 25 infusion bag(s).

Additionally, the following boxes may also be supplied in hospital packs of: *5, 10 or 20 **3, 6 or 10

Not all package sizes may be marketed.

Linezolid Taj Pharma 2mg/ml solution for infusion contains Linezolid Taj Pharma 2mg/ml in an isotonic, clear, colourless to yellow solution. Other ingredients are: glucose monohydrate, sodium citrate, citric acid anhydrous (E330), hydrochloric acid (E507; as 10% solution) for pH-adjustment or sodium hydroxide (10% solution) for pH-adjustment, water for injections.

Dosage and method of administration

Linezolid Taj Pharma should only be initiated in a hospital environment and after consultation with a relevant specialist such as a microbiologist or an infectious diseases specialist.

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 Taj Pharma has an oral bioavailability of approximately 100 %. The solution for infusion should be administered over a period of 30 to 120 minutes.

The recommended Linezolid Taj Pharma dosage should be administered intravenously (I.V.) twice daily.

Recommended dosage and duration for adults:

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 Taj Pharma have not yet been established for treatment periods longer than 28 days.

No increase in the recommended dosage or duration of treatment is required for infections associated with concurrent bacteraemia. The dose recommendation for the solution for infusion is as follows:

InfectionsDosage and route for twice daily administrationDuration of treatment
Nosocomial pneumonia 

600mg twice daily

 

 

10 – 14 Consecutive days

Community acquired pneumonia
Complicated skin and soft tissue infections 

600mg twice daily

Paediatric population: The safety and efficacy of Linezolid Taj Pharma in children aged (< 18 years old) has not been established. Currently available data are described in section 4.8, 5.1 and 5.2 of the Summary of Product Characteristics but no recommendation on a posology can be made.

Elderly: No dose adjustment is required.

Renal impairment: No dose adjustment is required.

Severe renal impairment (i.e. CLCR < 30ml/min): No dose adjustment is required. Due to the unknown clinical significance of higher exposure (up to 10-fold) to the two primary metabolites of Linezolid Taj Pharma in patients with severe renal insufficiency, Linezolid Taj Pharma should be used with special caution in these patients and only when the anticipated benefit is considered to outweigh the theoretical risk.

As approximately 30 % of a Linezolid Taj Pharma dose is removed during 3 hours of haemodialysis, Linezolid Taj Pharma should be given after dialysis in patients receiving such treatment. The primary metabolites of Linezolid Taj Pharma are removed to some extent by haemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency. Therefore, Linezolid Taj Pharma should be used with special caution in patients with severe renal insufficiency who are undergoing dialysis, and only when the anticipated benefit is considered to outweigh the theoretical risk.

To date, there is no experience of Linezolid Taj Pharma administration to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than haemodialysis).

Hepatic impairment: Patients with mild to moderate hepatic insufficiency (Child-Pugh class A or B): No dose adjustment is required.

Severe hepatic impairment (Child-Pugh class C):

As Linezolid Taj Pharma is metabolised by a non-enzymatic process, impairment of hepatic function would not be expected to significantly alter its metabolism and, therefore, no dose adjustment is recommended. However, there are limited clinical data and it is recommended that Linezolid Taj Pharma should be used in such patients only when the anticipated benefit is considered to outweigh the theoretical risk (see sections 4.4 and 5.2).

Contra-indications

Patients hypersensitive to Linezolid Taj Pharma or any of the excipients.

Linezolid Taj Pharma 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, Linezolid Taj Pharma 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.
  • Patients taking any of the following medications: 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. adrenaline / epinephrine, noradrenaline / norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), pethidine or buspirone.

Breast-feeding should be discontinued prior to and throughout administration (see section 4.6 of Summary of Product Characteristics).

Special warnings and precautions for use

Myelosuppression

Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving Linezolid Taj Pharma. In cases where the outcome is known, when Linezolid Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma regardless of baseline blood count.

In compassionate use studies, a higher incidence of serious anaemia was reported in patients receiving Linezolid Taj Pharma 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 Taj Pharma 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 Taj Pharma therapy for more than 28 days. Most patients fully or partially recovered following discontinuation of Linezolid Taj Pharma 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 Taj Pharma, 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 Taj Pharma 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 Taj Pharma 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 Taj Pharma should only be used in patients with known or possible co-infection with Gram negative organisms if there are no alternative treatment options available. 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 Taj Pharma 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 Taj Pharma. If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including Linezolid Taj Pharma, 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 Taj Pharma. 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 Taj Pharma should receive immediate medical attention. If lactic acidosis occurs, the benefits of continued use of Linezolid Taj Pharma should be weighed against the potential risks.

Mitochondrial dysfunction

Linezolid Taj Pharma 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.

Serotonin syndrome

Spontaneous reports of serotonin syndrome associated with the co-administration of Linezolid Taj Pharma and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been reported. Co-administration of Linezolid Taj Pharma and serotonergic agents is therefore contraindicated except where administration of Linezolid Taj Pharma 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 Taj Pharma; 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 Taj Pharma 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 Taj Pharma should be weighed against the potential risks.

There may be an increased risk of neuropathies when Linezolid Taj Pharma 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 Taj Pharma. 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 Taj Pharma is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the doses used for antibacterial therapy, it does not exert an anti-depressive effect. There are very limited data from drug interaction studies and on the safety of Linezolid Taj Pharma when administered to patients with underlying conditions and/or on concomitant medications which might put them at risk from MAO inhibition. Therefore, Linezolid Taj Pharma is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible.

Use with tyramine-rich foods

Patients should be advised against consuming large amounts of tyramine rich foods.

Superinfection

The effects of Linezolid Taj Pharma 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 Taj Pharma doses experienced drugrelated candidiasis during clinical trials. Should superinfection occur during therapy, appropriate measures should be taken.

Special populations

Linezolid Taj Pharma 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 4.2 and 5.2 of the Summary of Product Characteristics).

It is recommended that Linezolid Taj Pharma should be given to patients with severe hepatic insufficiency only when the perceived benefit outweighs the theoretical risk.

Impairment of fertility

Linezolid Taj Pharma 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 Taj Pharma on the human male reproductive system are not known.

Clinical trials

The safety and effectiveness of Linezolid Taj Pharma 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 Taj Pharma in the treatment of these conditions is limited.

Excipients

Eachml of the solution contains 48mg (i.e. 14.4 g/300ml) glucose. This should be taken into account in patients with diabetes mellitus or other conditions associated with glucose intolerance. Eachml of solution also contains 0.38mg (114mg/300ml) sodium. The sodium content should be taken into account in patients on a controlled sodium diet.

Interactions

Monoamine oxidase inhibitors

Linezolid Taj Pharma 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 Taj Pharma when administered to patients on concomitant medications that might put them at risk from MAO inhibition. Therefore, Linezolid Taj Pharma is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible.

Potential interactions producing elevation of blood pressure

In normotensive healthy volunteers, Linezolid Taj Pharma enhanced the increases in blood pressure caused by pseudoephedrine and phenylpropanolamine hydrochloride. Co-administration of Linezolid Taj Pharma with either pseudoephedrine or phenylpropanolamine resulted in mean increases in systolic blood pressure of the order of 30-40mm Hg, compared with 11-15 mm Hg increases with Linezolid Taj Pharma alone, 14-18 mm Hg with either pseudoephedrine or phenylpropanolamine alone and 8-11 mm Hg 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 Taj Pharma.

Potential serotonergic interactions

The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers.

Subjects were administered dextromethorphan (two 20mg doses given 4 hours apart) with or without Linezolid Taj Pharma. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis and hyperpyrexia) have been observed in normal subjects receiving Linezolid Taj Pharma and dextromethorphan.

Post marketing experience: there has been one report of a patient experiencing serotonin syndromelike effects while taking Linezolid Taj Pharma and dextromethorphan which resolved on discontinuation of both medications.

During clinical use of Linezolid Taj Pharma 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, management of patients for whom treatment with Linezolid Taj Pharma and serotonergic agents is essential, is described in special warnings and precautions for use.

Use with tyramine-rich foods

No significant pressor response was observed in subjects receiving both Linezolid Taj Pharma and less than 100mg 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 Taj Pharma 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 Taj Pharma does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug interactions are expected with Linezolid Taj Pharma.

Rifampicin

The effect of rifampicin on the pharmacokinetics of Linezolid Taj Pharma was studied in sixteen healthy adult male volunteers administered Linezolid Taj Pharma 600mg twice daily for 2.5 days with and without rifampicin 600mg once daily for 8 days. Rifampicin decreased the Linezolid Taj Pharma Cmax and AUC by a mean 21% [90% CI, 15, 27] and a mean 32% [90% CI, 27, 37], respectively. The mechanism of this interaction and its clinical significance are unknown.

Warfarin

When warfarin was added to Linezolid Taj Pharma 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 Taj Pharma to assess the clinical significance, if any, of these findings.

Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of Linezolid Taj Pharma in pregnant women. Studies in animals have shown reproductive toxicity. A potential risk for humans exists.

Linezolid Taj Pharma should not be used during pregnancy unless clearly necessary i.e. only if the potential benefit outweighs the theoretical risk.

Breast-feeding

Animal data suggest that Linezolid Taj Pharma and its metabolites may pass into breast milk and, accordingly, breastfeeding should be discontinued prior to and throughout administration.

Fertility

In animal studies, Linezolid Taj Pharma caused a reduction in fertility.

Effects on ability to drive and use machines

Patients should be warned about the potential for dizziness or symptoms of visual impairment whilst receiving Linezolid Taj Pharma and should be advised not to drive or operate machinery if any of these symptoms occurs.

Undesirable effects

The table below provides a listing of adverse drug reactions with frequency based on all-causality data from clinical studies that enrolled more than 2,000 adult patients who received the recommended Linezolid Taj Pharma doses for up to 28 days.

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.

Additional adverse reactions reported from post-marketing experience are included in the table with frequency category ‘Not known’, since the actual frequency cannot be estimated from the available

data.

The following undesirable effects have been observed and reported during treatment with Linezolid Taj Pharma

with the following frequencies: 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)

System Organ ClassCommon (≥1/100 to 10Uncommon (≥1/1,000 to <1/100Rare (≥1/1,000 to <1/1000 Very rare (≥1/1,000 to <1/10,000Frequency not known (cannot be estimated from available data)
Infections and infestationsCandidiasis, oral candidiasis, vaginal candidiasis, fungal infectionsVaginitisAntibioticassociated colitis, including pseudomemb ranous colitis*
Blood and the lymphatic system disordersAnaemia*†Leucopenia*, neutropenia, thrombocytop enia*, eosinophiliaPancytopenia *Myelosuppressio n*, sideroblastic anaemia*
Immune system disordersAnaphylaxis
Metabolism and nutrition disordersHyponatraemi aLactic acidosis*
Psychiatric disordersInsomnia
Nervous system disordersHeadache, taste perversion (metallic taste), DizzinessConvulsions*, hypoaesthesia , paraesthesiaSerotonin syndrome**, peripheral neuropathy*
Eye disordersBlurred vision*Changes in visual field defect*Optic neuropathy*, optic neuritis*, loss of vision*, changes in visual acuity*, changes in colour vision*
Ear and labyrinth disordersTinnitus
Cardiac disordersArrhythmia (tachycardia)
Vascular disordersHypertensionTransient ischaemic attacks, phlebitis, thrombophleb itis
Gastrointesti nal disorders

 

Diarrhoea, nausea, vomiting. localised or general abdominal pain, constipation, dyspepsiaPancreatitis, gastritis, abdominal distention, dry mouth, glossitis, loose stools, stomatitis, tongue discolouration or disorderSuperficial tooth discolouratio n
Hepato – biliary disordersAbnormal liver function test; increased AST, ALT or alkaline phosphataseIncreased total bilirubin
Skin and subcutaneous tissue disordersPruritus, rashUrticaria, dermatitis, diaphoresisBullous disorders such as those described as Stevens – Johnson
 syndrome and toxic epidermal necrolysis, angioedema, alopecia
Renal and urinary disordersIncreased BUNRenal failure, polyuria, increased creatinine
Reproductive system and breast disordersVulvovaginal disorder
General disorders and administratio n site conditionsFever, localised painChills, fatigue, injection site pain, increased thirst
InvestigationsChemistry Increased LDH, creatine kinase, lipase, amylase or non fasting glucose. Decreased total protein, albumin, sodium or calcium. Increased or decreased potassium or bicarbonate.

Haematology Increased neutrophils or eosinophils. Decreased haemoglobin, haematocrit or red blood cell count. Increased or decreased platelet or white blood cell counts

Chemistry Increased sodium or calcium. Decreased non fasting glucose. Increased or decreased chloride

Haematology Increased reticulocyte count. Decreased neutrophils.

 

 

The following adverse reactions to Linezolid Taj Pharma were considered to be serious in rare cases: localized abdominal pain, transient ischaemic attacks and hypertension.

†In controlled clinical trials where Linezolid Taj Pharma was administered for up to 28 days, 2.0% 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 Taj Pharma 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.

Paediatric population

Safety data from clinical studies based on more than 500 paediatric patients (from birth to 17 years) do not indicate that the safety profile of Linezolid Taj Pharma for paediatric patients differs from that for adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Overdose

No specific antidote is known.

No cases of overdose have been reported. However, the following information may prove useful:

Supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid Taj Pharma dose is removed during 3 hours of haemodialysis, but no data are available for the removal of Linezolid Taj Pharma by peritoneal dialysis or haemoperfusion.

Instructions for use and handling

For single use only. Remove overwrap only when ready to use, then check for minute leaks by squeezing the bag firmly. If the bag leaks, do not use as sterility may be impaired. The solution should be visually inspected prior to use and only clear solutions, without particles should be used. Do not use these bags in series connections. Any unused solution must be discarded. No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Do not reconnect partially used bags.

Linezolid Taj Pharma solution for infusion is compatible with the following solutions: 5 % glucose intravenous infusion, 0.9 % sodium chloride intravenous infusion, Ringer-lactate solution for injection (Hartmann’s solution for injection).

Incompatibilities

Additives should not be introduced into this solution. If Linezolid Taj Pharma is to be given concomitantly with other drugs, each drug should be given separately in accordance with its own directions for use.

Similarly, if the same intravenous line is to be used for sequential infusion of several drugs, the line should be flushed prior to and following Linezolid Taj Pharma administration with a compatible infusion solution.

Linezolid Taj Pharma solution for infusion is known to be physically incompatible with the following compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium and sulphamethoxazole / trimethoprim. Additionally, it is chemically incompatible with ceftriaxone sodium.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Shelf life

Before opening: 30 months

After opening: From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Special precautions for storage

Store in the original package (overwrap and carton) in order to protect from light.