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Package leaflet: Information for the user Linezolid 600mg film-coated tablets

Linezolid

Read all of this leaflet carefully before you start taking 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, or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If you get any side effects, talk to your doctor, or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Linezolid is and what it is used for

2.    What you need to know before you take Linezolid

3.    How to take Linezolid

4.    Possible side effects

5.    How to store Linezolid

6.    Contents of the pack and other information

1. What Linezolid is and what it is used for

Linezolid 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 is suitable to treat your infection.

2. What you need to know before you take Linezolid

Do not take Linezolid

•    if you are allergic (hypersensitive) to linezolid or any of the other ingredients of this medicine)

•    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 passes into breast milk and could affect the baby. Warnings and precautions

Linezolid 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?

•    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?

•    Are you taking any of the following medicines?

-    decongestant cold or flu remedies containing pseudoephedrine or phenylpropanolamine

-    medicines used to treat asthma such as salbutamol, terbutaline, fenoterol

-    antidepressants known as tricyclics or SSRIs (selective serotonin reuptake inhibitors) for example amitriptyline, cipramil, 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

-    an antibiotic called rifampicin Take special care with Linezolid

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. If this becomes severe or persistent or you notice that your stools contains blood or mucus, you should stop taking Linezolid 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

There is a risk that Linezolid 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 must not be taken if you are already taking these medicines or have taken them recently. (See also Section 2 above 'Do not take Linezolid'

•    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, 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, cipramil, 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.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Linezolid with food and drink

•    You can take Linezolid 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 Linezolid 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 in pregnant women is not known. Therefore it should not be taken in pregnancy unless advised by your doctor. If you are pregnant, think you may be pregnant or are planning have a baby, ask your doctor or pharmacist for advice before taking this medicine.

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

Driving and using machines

Linezolid 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 contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take Linezolid

Adults

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The usual dose is one tablet (600mg linezolid) twice daily (every twelve hours). Swallow the tablet whole with some water.

If you are on kidney dialysis, you should take Linezolid after 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 taking Linezolid, your doctor should perform regular blood tests to monitor your blood count.

Your doctor should monitor your eyesight if you take Linezolid more for than 28 days.

Use in children

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

SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Linezolid 600 mg Film-Coated Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Linezolid 600 mg Film-Coated Tablets

Excipient(s) with known effect: each Linezolid film-coated tablet contains 222 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Linezolid 600 mg Film-Coated Tablets Film-coated tablet.

White to off white, oval shaped, approx 18.4 mm in length and 9.6 mm in width film-coated tablet with "I"on one side and "22" on the other side

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Nosocomial pneumonia Community acquired pneumonia

Linezolid 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 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 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 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 is not active against infections caused by Gram negative pathogens. Linezolid should only be used in patients with complicated skin and soft tissue infections with known or possible co-infection 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 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.

4.2    Posology and method of administration

Posology:

Linezolid film-coated tablets 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 has an oral bioavailability of approximately 100%.

Recommended dosaoe and duiation of tieatment foi 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 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 tablets is as follows:

Paediattic population: There are insufficient data on the safety and efficacy of linezolid in children and adolescents (< 18 years old) to establish dosage recommendations (see sections 5.1 and 5.2). Therefore, until further data are available, use of linezolid in this age group is not recommended.

Eldeily patients: No dose adjustment is required.

Patients with lenalinsufficiency: No dose adjustment is required (see sections 4.4 and 5.2). Pams witi s_me ienal    (e, ^< 0 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 in patients with severe renal insufficiency, linezolid 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 dose is removed during 3 hours of haemodialysis, linezolid should be given after dialysis in patients receiving such treatment. The primary metabolites of linezolid 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 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 administration to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than haemodialysis).

Patients with hepatic insufficiency: No dose adjustment is required. However, there are limited clinical data and it is recommended that linezolid 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 administiation: The recommended linezolid dosage should be administered intravenously or orally twice daily.

Route of administration: Oral use.

The film-coated tablets may be taken with or without food.

4.3    Contraindications

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

Linezolid 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 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-HT1 receptor agonists (triptans), directly and indirectly acting sympathomimetic agents (including the adrenergic bronchodilators, pseudoephedrine and phenylpropanolamine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), pethidine or buspirone.

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

4.4    Special warnings and precautions for use

Mvelosuooiession

Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected haematologic parameters have risen toward pretreatment levels. The risk of these effects appears to be related to the duration of treatment. Elderly patients treated with linezolid may be at greater risk of experiencing blood dyscrasias than younger patients. Thrombocytopenia may occur more commonly in patients with severe renal insufficiency, whether or not on dialysis. Therefore, close monitoring of blood counts is recommended in patients who: have pre-existing anaemia, granulocytopenia or thrombocytopenia; are receiving concomitant medications that may decrease haemoglobin levels, depress blood counts or adversely affect platelet count or function; have severe renal insufficiency; receive more than 10-14 days of therapy Linezolid should be administered to such patients only when close monitoring of haemoglobin levels, blood counts and platelet counts is possible.

If significant myelosuppression occurs during linezolid therapy, treatment should be stopped unless it is considered absolutely necessary to continue therapy, in which case intensive monitoring of blood counts and appropriate management strategies should be implemented. In addition, it is recommended that complete blood counts (including haemoglobin levels, platelets, and total and differentiated leucocyte counts) should be monitored weekly in patients who receive linezolid regardless of baseline blood count.

In compassionate use studies, a higher incidence of serious anaemia was reported in patients receiving linezolid for more than the maximum recommended duration of 28 days. These patients more often required blood transfusion. Cases of anaemia requiring blood transfusion have also been reported post marketing, with more cases occurring in patients who received linezolid therapy for more than 28 days.

Cases of sideroblastic anaemia have been reported post-marketing. Where time of onset was known, most patients had received linezolid therapy for more than 28 days. Most patients fully or partially recovered following discontinuation of linezolid with or without treatment for their anaemia.

MottaUQiimbalance in a clinicaltiialin patients with cathetei-ielated Giam positive bloodstieam infections

Excess mortality was seen in patients treated with linezolid, relative to vancomycin/dicloxacillin/oxacillin, in an open-label study in seriously ill patients with intravascular catheter-related infections [78/363 (21.5%) vs 58/363 (16.0%)]. The main factor influencing the mortality rate was the Gram positive infection status at baseline. Mortality rates were similar in patients with infections caused purely by Gram positive organisms (odds ratio 0.96; 95% confidence interval: 0.58-1.59) but were significantly higher (p=0.0162) in the linezolid arm in patients with any other pathogen or no pathogen at baseline (odds ratio 2.48; 95% confidence interval: 1.38-4.46). The greatest imbalance occurred during treatment and within 7 days following discontinuation of study drug. More patients in the linezolid arm acquired Gram negative pathogens during the study and died from infection caused by Gram negative pathogens and polymicrobial infections. Therefore, in complicated skin and soft tissue infections linezolid should only be used in patients with known or possible co-infection with Gram negative organisms if there are no alternative treatment options available (see section 4.1). In these circumstances treatment against Gram negative organisms must be initiated concomitantly.

Antibiotic-associated diaiihoea and colitis

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including linezolid. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of any antibacterial agent. In cases of suspected or verified antibiotic-associated colitis, discontinuation of linezolid may be warranted. Appropriate management measures should be instituted. Antibiotic-associated diarrhoea and antibiotic-associated colitis, including pseudomembranous colitis and Clostridium difficile-associated diarrhoea, has been reported in association with the use of nearly all antibiotics including linezolid and may range in severity from mild diarrhoea to fatal colitis. Therefore, it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of linezolid. If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including linezolid, should be discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.

Lactic acidosis

Lactic acidosis has been reported with the use of linezolid. Patients who develop signs and symptoms of metabolic acidosis including recurrent nausea or vomiting, abdominal pain, a low bicarbonate level, or hyperventilation while receiving linezolid should receive immediate medical attention. If lactic acidosis occurs, the benefits of continued use of linezolid should be weighed against the potential risks.

Mitochondiial dysfunction

Linezolid inhibits mitochondrial protein synthesis. Adverse events, such as lactic acidosis, anaemia and neuropathy (optic and peripheral), may occur as a result of this inhibition; these events are more common when the drug is used longer than 28 days.

Seiotonin syndrome

Spontaneous reports of serotonin syndrome associated with the co-administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been reported. Co-administration of linezolid and serotonergic agents is therefore contraindicated (see section 4.3) except where administration of linezolid and concomitant serotonergic agents is essential. In those cases patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur physicians should consider discontinuing either one or both agents; if the concomitant serotonergic agent is withdrawn, discontinuation symptoms can occur. Peiipheial and optic neuiopathy

Peripheral neuropathy, as well as optic neuropathy and optic neuritis sometimes progressing to loss of vision, have been reported in patients treated with linezolid; these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days.

All patients should be advised to report symptoms of visual impairment, such as changes in visual acuity, changes in colour vision, blurred vision, or visual field defect. In such cases, prompt evaluation is recommended with referral to an ophthalmologist as necessary. If any patients are taking Linezolid for longer than the recommended 28 days, their visual function should be regularly monitored.

If peripheral or optic neuropathy occurs, the continued use of Linezolid should be weighed against the potential risks.

There may be an increased risk of neuropathies when linezolid is used in patients currently taking or who have recently taken antimycobacterial medications for the treatment of tuberculosis.

Convulsions

Convulsions have been reported to occur in patients when treated with linezolid. In most of these cases, a history of seizures or risk factors for seizures was reported. Patients should be advised to inform their physician if they have a history of seizures.

Monoamine oxidase inhibitois

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

Use with tyiamine-iich foods

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

Supeiinfection

The effects of linezolid therapy on normal flora have not been evaluated in clinical trials. The use of antibiotics may occasionally result in an overgrowth of non-susceptible organisms. For example, approximately 3% of patients receiving the recommended linezolid doses experienced drug-related candidiasis during clinical trials. Should superinfection occur during therapy, appropriate measures should be taken.

Special populations

Linezolid should be used with special caution in patients with severe renal insufficiency and only when the anticipated benefit is considered to outweigh the theoretical risk (see sections 4.2 and 5.2).

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

Impaiiment of feitility

Linezolid reversibly decreased fertility and induced abnormal sperm morphology in adult male rats at exposure levels approximately equal to those expected in humans; possible effects of linezolid on the human male reproductive system are not known (see section 5.3). Clinical tiials

The safety and effectiveness of linezolid when administered for periods longer than 28 days have not been established.

Controlled clinical trials did not include patients with diabetic foot lesions, decubitus or ischaemic lesions, severe burns or gangrene. Therefore, experience in the use of linezolid in the treatment of these conditions is limited.

As the tablets contain lactose, Linezolid is not recommended for patients with rare hereditary problems of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.

4.5 Interaction with other medicinal products and other forms of interaction

Monoamine oxidase inhibitois Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). There are very limited data from drug interaction studies and on the safety of linezolid when administered to patients on concomitant medications that might put them at risk from MAO inhibition. Therefore, linezolid is not recommended for use in these circumstances unless close observation and monitoring of the recipient is possible (see sections 4.3 and 4.4).

Potentialinteiactions pioducino elevation of blood piessuie

In normotensive healthy volunteers, linezolid enhanced the increases in blood pressure caused by pseudoephedrine and phenylpropanolamine hydrochloride. Co-administration of linezolid with either pseudoephedrine or phenylpropanolamine resulted in mean increases in systolic blood pressure of the order of 30-40 mmHg, compared with 11-15 mmHg increases with linezolid alone, 14-18 mmHg with either pseudoephedrine or phenylpropanolamine alone and 8-11 mmHg with placebo. Similar studies in hypertensive subjects have not been conducted. It is recommended that doses of drugs with a vasopressive action, including dopaminergic agents, should be carefully titrated to achieve the desired response when co-administered with linezolid.

Potential seiotoneioic inteiactions

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

Post marketing experience: there has been one report of a patient experiencing serotonin syndrome-like effects while taking linezolid and dextromethorphan which resolved on discontinuation of both medications.

During clinical use of linezolid with serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), cases of serotonin syndrome have been reported. Therefore, while co-administration is contraindicated (see section 4.3), management of patients for whom treatment with linezolid and serotonergic agents is essential, is described in section 4.4.

Use with tyiamine-iich foods

No significant pressor response was observed in subjects receiving both linezolid and less than 100 mg tyramine. This suggests that it is only necessary to avoid ingesting excessive amounts of food and beverages with a high tyramine content (e.g. mature cheese, yeast extracts, undistilled alcoholic beverages and fermented soya bean products such as soy sauce).

Diuos metabolised by cvtochiome P450

Linezolid is not detectably metabolised by the cytochrome P450 (CYP) enzyme system and it does not inhibit any of the clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Similarly, linezolid does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug interactions are expected with linezolid.

Rifampicin

The effect of rifampicin on the pharmacokinetics of linezolid was studied in sixteen healthy adult male volunteers administered linezolid 600 mg twice daily for 2.5 days with and without rifampicin 600 mg once daily for 8 days. Rifampicin decreased the linezolid 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. Waifaiin

When warfarin was added to linezolid therapy at steady-state, there was a 10% reduction in mean maximum INR on co-administration with a 5% reduction in AUC INR. There are insufficient data from patients who have received warfarin and linezolid to assess the clinical significance, if any, of these findings.

4.6    Fertility, pregnancy and lactation

Pieonancy

There are no adequate data from the use of linezolid in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). A potential risk for humans exists. Linezolid should not be used during pregnancy unless clearly necessary i.e. only if the potential benefit outweighs the theoretical risk.

Bieast-feeding

Animal data suggest that linezolid and its metabolites may pass into breast milk and, accordingly, breast-feeding should be discontinued prior to and throughout administration.

Feitility

In animal studies, linezolid caused a reduction in fertility (see section 5.3).

4.7    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 and should be advised not to drive or operate machinery if any of these symptoms occurs.

4.8    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 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 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)