sign in sign up
<<
Home , Linezolid

NA LINEZOLID IE

Package leaflet: Information for the user Numbness, tingling or blurred vision have been reported by patients • Decrease of the blood cell count pathogens. Specific therapy against Gram negative organisms must be Patients with hepatic insufficiency: Patients with mild to moderate -- medicines used to treat moderate to severe pain, such as are pregnant, think you may be pregnant or are planning to have a baby, who have been given Linezolid for more than 28 days. If you experience • Weakness and/or sensory changes initiated concomitantly if co- with a Gram negative pathogen is hepatic insufficiency (Child-Pugh class A or B): No dose adjustment is Linezolid 2 mg/ml solution for infusion -- medicines used to treat anxiety disorders, such as ask your doctor or pharmacist for advice before taking this medicine. difficulties with your vision you should consult your doctor as soon as Reporting of side effects documented or suspected. required. -- an called You should not breast-feed when taking Linezolid because it passes into possible. If you get any side effects, talk to your doctor or pharmacist or nurse. This Description Patients with severe hepatic insufficiency (Child-Pugh class C): As Linezolid Take special care with Linezolid and could affect the baby. Other side effects include: includes any possible side effects not listed in this leaflet. You can also For single use only. The bag holds 300 ml solution and is packaged in a linezolid is metabolised by a non-enzymatic process, impairment of report side effects directly via HPRA Pharmacovigilance, Earlsfort Terrace, box. Each box contains 1 or 10 infusion bags. hepatic function would not be expected to significantly alter its prva stran prva Tell your doctor before you are treated with this medicine if you: Driving and using machines Common side effects (may affect up to 1 in 10 people): Read all of this leaflet carefully before this medicinal product is • bruise and bleed easily Linezolid may make you feel dizzy or experience problems with your • Fungal especially vaginal or oral “thrush” IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Linezolid 2 mg/ml solution for infusion contains linezolid 2 mg/ml in a and, therefore, no dose adjustment is recommended. However, there are given to you because it contains important information for you. • are anaemic (have low red blood cells) vision. If this happens, do not drive or operate any machinery. Remember • Website: www.hpra.ie; E-mail: [email protected]. clear, colourless to yellow or to yellowish-brown solution. Other no pharmacokinetic data and limited clinical experience of linezolid in • Keep this leaflet. You may need to read it again. • are prone to getting infections that if you are unwell your ability to drive or operate machinery may be • Metallic taste in the mouth By reporting side effects you can help provide more information on the ingredients are glucose monohydrate, sodium citrate dihydrate, citric acid patients with severe hepatic insufficiency. Linezolid should be used with • If you have any further questions, ask your doctor or pharmacist or • have a history of affected. • Diarrhoea, or vomiting safety of this medicine. anhydrous, hydrochloric acid, sodium hydroxide and water for injection. special caution in patients with severe hepatic insufficiency and only when nurse. the anticipated benefit is considered to outweigh the theoretical risk. • have problems or problems particularly if you are on dialysis Linezolid contains glucose. • Changes in some blood test results including those measuring your Dosage and method of administration 90 mm ± 0,5 mm - zaetek teksta • If you get any side effects, talk to your doctor or pharmacist or nurse. • have diarrhoea kidney or liver function or blood sugar levels 5. How to store Linezolid Linezolid should only be initiated in a hospital environment and after Contraindications This includes any possible side effects not listed in this leaflet. See 300 ml of solution for infusion contains 13.7 g glucose. This should be Tell your doctor immediately if during treatment you suffer from: taken into account in patients with diabetes mellitus. • Unexplained bleeding or bruising, which may be due to changes in the Keep this medicine out of the sight and reach of children. consultation with a relevant specialist such as a microbiologist or an Hypersensitivity to linezolid or to any of the excipients. section 4. numbers of certain cells in the blood which may affect blood clotting or infectious diseases specialist. • problems with your vision such as blurred vision, changes in colour Do not use this medicine after the expiry date which is stated on the Linezolid should not be used in patients taking any medicinal product Linezolid contains sodium. lead to anaemia What is in this leaflet vision, difficulty in seeing detail or if your field of vision becomes 300 ml of solution for infusion contains 114 mg sodium (5 mmol). To be packaging after EXP. The expiry date refers to the last day of that month. Patients who commence treatment on the parenteral formulation may be which inhibits monoamine oxidases A or B (e.g. , restricted. • Difficulty in sleeping switched to either oral presentation when clinically indicated. In such , , ) or within two weeks of taking any 1. What Linezolid is and what it is used for taken into consideration by patients on a controlled sodium diet. Do not store above 30°C. • loss of sensitivity in your arms or legs or a sensation of tingling or • Increased blood pressure circumstances, no dose adjustment is required as linezolid has an oral such medicinal drug. 2. What you need to know before you are treated with Linezolid • Anaemia (low red blood cell) Store in the original package in order to protect from light. 3. How Linezolid is given pricking in your arms or legs. of approximately 100 %. Unless there are facilities available for close observation and monitoring smer branja kode 3. How Linezolid is given • Changes in numbers of certain cells in the blood which may affect your After opening: Chemical and physical in-use stability has been 4. Possible side effects • You may develop diarrhoea while taking or after taking , The solution for infusion should be administered over a period of 30 to 120 of blood pressure, linezolid should not be administered to patients with Adults ability to fight infection demonstrated for 24 hours at room temperature in primary bag after 5. How to store Linezolid including Linezolid. If this becomes severe or persistent or you notice minutes. the following underlying clinical conditions or on the following types of This medicine will be given to you through a drip (by infusion into a vein) • rash removal of the secondary pack (pouch). From a microbiological point of 6. Contents of the pack and other information that your stools contains blood or mucus, you should stop taking The recommended linezolid dosage should be administered IV twice daily. concomitant medications: Linezolid immediately and consult your doctor. In this situation, you by a doctor or healthcare professional. The usual dose for adults (18 • Itching skin view, the product should be used immediately. If not used immediately, Linezolid Recommended dosage and duration for adults: • Patients with uncontrolled hypertension, phaeochromocytoma, should not take medicines that stop or slow bowel movement. years and older) is 300 ml (600 mg linezolid) twice daily which is given • Dizziness in-use storage times and conditions prior to use are the responsibility of The duration of treatment is dependent on the pathogen, the site of carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder, Linezolid 1. What Linezolid is and what it is used for • recurrent nausea or vomiting, abdominal pain or rapid breathing. directly into the blood stream (intravenously) by a drip over a period of 30 • Localised or general abdominal pain the user. Linezolid is an antibiotic of the oxazolidinones group that works by to 120 minutes. • Constipation infection and its severity, and on the patient’s clinical response. acute confusional states. Other medicines and Linezolid Do not use this medicine if you notice that solution is not clear, colourless stopping the growth of certain (germs) that cause infections in • Indigestion The following recommendations for duration of therapy reflect those used • Patients taking any of the following medications: re-uptake There is a risk that Linezolid may sometimes interact with certain other If you are on kidney dialysis, you should be given Linezolid after dialysis. to yellow or to yellowish-brown. adults. It is used to treat and some infections in the skin or • Localised pain in the clinical trials. Shorter treatment regimens may be suitable for some inhibitors, tricyclic , serotonin 5-HT1 receptor agonists medicines to cause side effects such as changes in blood pressure, A course of treatment usually lasts 10 to 14 days, but can last up to 28 Do not throw away any medicines via wastewater or household waste. under the skin. Your doctor will have decided if Linezolid is suitable to • Fever types of infection but have not been evaluated in clinical trials. (triptans), directly and indirectly acting sympathomimetic agents temperature or heart rate. days. The safety and effectiveness of this medicine have not been Ask your pharmacist how to throw away medicines you no longer use. (including the adrenergic bronchodilators, and smer branja kode treat your infection. Uncommon side effects (may affect up to 1 in 100 people): The maximum treatment duration is 28 days. The safety and effectiveness Tell your doctor if you are taking or have taken within the last 2 established for treatment periods longer than 28 days. Your doctor will These measures will help protect the environment. ), vasopressive agents (e.g. / • Inflammation of the vagina or genital area in women of linezolid have not yet been established for treatment periods longer weeks the following medicines as Linezolid must not be taken if you are decide how long you should be treated. epinephrine, noradrenaline / ), dopaminergic agents (e.g. 2. What you need to know before you are treated with • Sensations such as tingling or feeling numb than 28 days. already taking these medicines or have taken them recently (see also While you are taking Linezolid, your doctor should perform regular blood 6. Contents of the pack and other information , dobutamine), pethidine or buspirone. • Blurred vision No increase in the recommended dosage or duration of treatment is Linezolid Linezolid Section 2 above ‘You should not be treated with Linezolid ’). tests to monitor your blood count. Breast feeding should be discontinued prior to and throughout • “Ringing” in the ears (tinnitus) What Linezolid contains required for infections associated with concurrent bacteraemia. The dose Linezolid You should not be treated with Linezolid: • inhibitors (MAOIs; for example phenelzine, Your doctor should monitor your eyesight if you take Linezolid for more • Inflammation of the veins • The active substance is linezolid. 1 ml of solution for infusion contains administration. xxxxxx isocarboxazid, selegiline, moclobemide). These may be used to treat recommendation for the solution for infusion and the tablets/granules for • if you are allergic to linezolid or any of the other ingredients of this than 28 days. • Dry or sore mouth , swollen, sore, or discoloured tongue 2 mg linezolid. Each 300 ml infusion bag contains 600 mg linezolid. Special warnings and precautions for use depression or Parkinson’s disease. oral suspension are identical and are as follows: medicine (listed in section 6). • Pain at and around the place where the infusion (drip) was given • The other ingredients are glucose monohydrate, sodium citrate Myelosuppression Use in children and adolescents Dosage and route • if you are taking or have taken within the last 2 weeks any medicines Also tell your doctor if you are taking the following medicines. Your doctor • Inflammation of the veins (including where the infusion (drip) was given) dihydrate, citric acid anhydrous, hydrochloric acid (for pH-adjustment), Myelosuppression (including anaemia, leucopenia, pancytopenia and 4 vizualna koda Linezolid is not normally used to treat children and adolescents (under 18 Infections for twice daily Duration of treatment known as monoamine oxidase inhibitors. (MAOIs: for example may still decide to give you Linezolid, but will need to check your general • A need to urinate more often sodium hydroxide (for pH-adjustment) and water for injections. See ) has been reported in patients receiving linezolid. In years old). administration phenelzine, isocarboxazid, selegiline, moclobemide). These medications health and your blood pressure before and during your treatment. In other • Chills section 2 “Linezolid contains glucose and sodium.” cases where the outcome is known, when linezolid was discontinued, the 75 mm ± 0,5 mm may be used to treat depression or Parkinson’s disease. If you receive more Linezolid than you should Nosocomial cases, your doctor may decide that another treatment is better for you. • Feeling tired or thirsty What Linezolid looks like and contents of the pack affected haematologic parameters have risen toward pretreatment levels. • if you are breast-feeding. This is because Linezolid passes into breast If you are concerned that you may have been given too much Linezolid, pneumonia • Decongestant cold or flu remedies containing pseudoephedrine or • Inflammation of the pancreas Clear colourless to yellow or to yellowish-brown solution (pH: 4.6 – 5.2, 600 mg twice daily The risk of these effects appears to be related to the duration of milk and could affect the baby. tell your doctor or a nurse at once. phenylpropanolamine. • Increased sweating osmolality: 270 mOsmol/kg – 320 mOsmol/kg). Community acquired treatment. Elderly patients treated with linezolid may be at greater risk of Warnings and precautions If you miss a dose of Linezolid • Changes in , salts or enzymes in the blood which measure pneumonia experiencing blood dyscrasias than younger patients. Thrombocytopenia • Some medicines used to treat asthma such as salbutamol, terbutaline, Linezolid solution for infusion: 10-14 Consecutive Talk to your doctor or pharmacist or nurse before you are treated with As you will be given this medicine under close supervision, it is very kidney or liver function. Complicated skin and may occur more commonly in patients with severe renal insufficiency, fenoterol. Primary packaging: Days Linezolid. unlikely that you will miss a dose. If you think that you have missed a dose • Convulsions soft tissue infections 600 mg twice daily whether or not on dialysis. Therefore, close monitoring of blood counts is • Certain antidepressants known as tricyclics or SSRIs (selective multilayer polyolefin plastic bag (300 ml) with multilayer polyolefin plastic Linezolid may not be suitable for you if you answer yes to any of the of treatment, tell a doctor or nurse at once. • Hyponatraemia (low blood sodium levels) recommended in patients who: have pre-existing anaemia, serotonin reuptake inhibitors). There are many of these, including port tube and polyolefin twist off connector.

213 mm ± 0,5 213 following questions. In this case tell your doctor as he/she will need to • granulocytopenia or thrombocytopenia; are receiving concomitant , cipramil, , , , , If you have any further questions on the use of this medicine, ask your Secondary packaging: Paediatric population: There are insufficient data on the , check your general health and your blood pressure before and during your • Reduction in platelets medications that may decrease haemoglobin levels, depress blood counts , , , , . doctor, pharmacist or nurse. Overpouch bag made of multilayer film. Film layers of bag from outside to safety and of linezolid in children and adolescents (< 18 years old) treatment or may decide that another treatment is better for you. • Abdominal bloating or adversely affect platelet count or function; have severe renal • Medicines used to treat migraine such as sumatriptan and zolmitriptan. inside: polyester, aluminium, polyester, propylene, 1 and 10 in a box. to establish dosage recommendations. Therefore, until further data are Ask your doctor if you are not sure whether these categories apply to you. • Medicines used to treat sudden, severe allergic reactions such as • Transient ischaemic attacks (temporary disturbance of blood flow to the available, use of linezolid in this age group is not recommended. insufficiency; receive more than 10-14 days of therapy. Linezolid should • Do you have high blood pressure, whether or not you are taking adrenaline (epinephrine). 4. Possible side effects brain causing short term symptoms such as loss of vision, leg and arm Not all pack sizes may be marketed. be administered to such patients only when close monitoring of Elderly patients: No dose adjustment is required. medicines for this? • Medicines which increase your blood pressure, such as noradrenaline Like all medicines, this medicine can cause side effects, although not weakness, slurring of speech and loss of consciousness). Marketing Authorisation Holder and Manufacturer haemoglobin levels, blood counts and platelet counts is possible.

173 mm ± 0,5 173 everybody gets them. Patients with renal insufficiency: No dose adjustment is required. • Have you been diagnosed with an overactive thyroid? (norepinephrine) dopamine and dobutamine. • Injection site pain KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia If significant myelosuppression occurs during linezolid therapy, treatment • Do you have a tumour of the adrenal glands (phaeochromocytoma) or • Medicines used to treat moderate to severe pain, such as pethidine. Tell your doctor, nurse or pharmacist immediately if you notice any of • Inflammation of the skin This medicinal product is authorised in the Member States of the Patients with severe renal insufficiency (i.e. CLCR < 30 ml/min): No dose should be stopped unless it is considered absolutely necessary to carcinoid syndrome (caused by tumours of the hormone system with • Medicines used to treat anxiety disorders, such as buspirone. these side effects during your treatment with Linezolid: • Increase in creatinine EEA under the following names: adjustment is required. Due to the unknown clinical significance of higher continue therapy, in which case intensive monitoring of blood counts and - PMS-433U-KRKA symptoms of diarrhoea, flushing of the skin, wheezing)? • Medicines that stop blood clotting, such as warfarin. • Stomach pain • skin reactions such as red sore skin and flaking (dermatitis), rash, Austria, Hungary, Czech Republic, Slovak Republic, exposure (up to 10-fold) to the two primary metabolites of linezolid in appropriate management strategies should be implemented. • Do you suffer from manic depression, schizoaffective disorder, mental itching, or swelling, particularly around the face and neck. This may be • Changes in heart rate (e.g. increase rate) patients with severe renal insufficiency, linezolid should be used with Tell your doctor or pharmacist if you are taking or have recently taken or Estonia, Latvia, Lithuania, Poland, Slovenia, In addition, it is recommended that complete blood counts (including confusion or other mental problems? Linezolid might take any other medicines. the sign of an allergic reaction and it may be necessary for you to stop Rare side effects (may affect up to 1 in 1000 people): Croatia, Romania, Italy, Spain, Ireland, United special caution in these patients and only when the anticipated benefit is • Are you taking any of the following medicines? haemoglobin levels, platelets, and total and differentiated leucocyte taking Linezolid. • Restricted field of vision Kingdom considered to outweigh the theoretical risk. -- decongestant, cold or flu remedies containing pseudoephedrine or Linezolid with food and drink counts) should be monitored weekly in patients who receive linezolid • problems with your vision such as blurred vision, changes in colour • Superficial tooth discolouration, removable with professional dental As approximately 30 % of a linezolid dose is removed during 3 hours of phenylpropanolamine • You can take Linezolid either before, during or after a meal. Bulgaria Линезолид Крка regardless of baseline blood count. iKRKk vision, difficulty in seeing detail or if your field of vision becomes cleaning (manual descaling) haemodialysis, Linezolid should be given after dialysis in patients -- medicines used to treat asthma such as salbutamol, terbutaline, • Avoid eating large amounts of mature cheese, yeast extracts, or soya France Linézolide Krka In compassionate use studies, a higher incidence of serious anaemia was restricted. The following side effects have also been reported (frequency cannot receiving such treatment. The primary metabolites of linezolid are Šifra: xxxxxx fenoterol bean extracts e.g. soy sauce and drinking alcohol, especially draught Germany Linezolid TAD reported in patients receiving linezolid for more than the maximum • severe diarrhoea containing blood and/or mucus (antibiotic associated be estimated from the available data): removed to some extent by haemodialysis, but the concentrations of Emb. mat.: NA LINEZOLID -- antidepressants known as tricyclics or SSRIs (selective serotonin beers and wine. This is because Linezolid may react with a substance recommended duration of 28 days. These patients more often required including pseudomembranous colitis), which in rare circumstances • (symptoms include fast heart rate, confusion, these metabolites are still very considerably higher following dialysis than IE reuptake inhibitors) for example amitriptyline, cipramil, clomipramine, called which is naturally present in some foods. This interaction This leaflet was last revised in blood transfusion. Cases of anaemia requiring blood transfusion have may develop into complications that are life-threatening. abnormal sweating, hallucinations, involuntary movements chills and those observed in patients with normal renal function or mild to moderate Dimenzije: 289 ± 0,5 mm x 730 ± 0,8 mm dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, may cause an increase in your blood pressure. ------also been reported post marketing, with more cases occurring in patients • recurrent nausea or vomiting, abdominal pain or rapid breathing. shivering) renal insufficiency. Therefore, linezolid should be used with special caution Material: papir tip C paroxetine, sertraline • If you develop a throbbing headache after eating or drinking, tell your The following information is intended for healthcare professionals only: who received linezolid therapy for more than 28 days. • fits or seizures have been reported with Linezolid. You should let your • (symptoms include recurrent nausea and vomiting, in patients with severe renal insufficiency who are undergoing dialysis, PhC št.: xxx -- medicines used to treat migraine such as sumatriptan and zolmitriptan doctor or pharmacist immediately. doctor know if you experience agitation, confusion, delirium, rigidity, abdominal pain, rapid breathing) Linezolid 2 mg/ml solution for infusion and only when the anticipated benefit is considered to outweigh the Cases of sideroblastic anaemia have been reported post-marketing. Merilo: 1:1 -- medicines used to treat sudden, severe allergic reactions such as Pregnancy and breast-feeding and fertility tremor, incoordination and while also taking antidepressants • Severe skin disorders Linezolid theoretical risk. Where time of onset was known, most patients had received linezolid Datum: 29.11.2016 adrenaline (epinephrine) The effect of Linezolid in pregnant women is not known. Therefore, it known as SSRI’s (see section 2). IMPORTANT: Refer to Summary of Product Characteristics before therapy for more than 28 days. Most patients fully or partially recovered • Sideroblastic anaemia ( a type of anaemia (low red blood cells)) To date, there is no experience of linezolid administration to patients Izdelal: K. Savnik -- medicines which increase your blood pressure, such as noradrenaline should not be taken in pregnancy unless advised by your doctor. If you prescribing. following discontinuation of linezolid with or without treatment for their • Alopecia (hair loss) undergoing continuous ambulatory peritoneal dialysis (CAPD) or Pregledal: K. Peric (norepinephrine), dopamine and dobutamine anaemia. • Changes in colour vision or difficulty in seeing detail Linezolid is not active against infections caused by Gram negative alternative treatments for renal failure (other than haemodialysis). Oddelek za oblikovanje

smer branja kode 450 mm ± 0,5 mm

DPMockUp060025_2 450 mm ± 0,5 mm smer branja kode NA LINEZOLID IE

Mortality imbalance in a in patients with catheter-related Gram linezolid. In most of these cases, a history of seizures or risk factors for receiving linezolid and dextromethorphan. positive seizures was reported. Patients should be advised to inform their IMIII Post marketing experience: there has been one report of a patient Frequency not known * See section ”Special Warnings and precautions for use”. Excess mortality was seen in patients treated with linezolid, relative to physician if they have a history of seizures. Common Uncommon Rare experiencing serotonin syndrome-like effects while taking linezolid and System Organ Class (cannot be estimated from ** See sections ”Contraindications” and ”Interactions” //, in an open-label study in seriously ill Monoamine oxidase inhibitors dextromethorphan which resolved on discontinuation of both medications. (≥1/100 to <1/10) (≥1/1,000 to <1/100) (≥1/10,000 to <1/1,000) available data) † See below patients with intravascular catheter-related infections [78/363 (21.5%) vs Linezolid is a reversible, non-selective inhibitor of monoamine oxidase 58/363 (16.0%)]. The main factor influencing the mortality rate was the During clinical use of linezolid with agents, including , oral The following adverse reactions to linezolid were considered to be serious (MAOI); however, at the doses used for antibacterial therapy, it does not antidepressants such as selective serotonin reuptake inhibitors (SSRIs), antibiotic-associated colitis, druga stran druga Gram positive infection status at baseline. Mortality rates were similar in Infections and candidiasis, vaginal in rare cases: localised abdominal pain, transient ischaemic attacks and exert an anti-depressive effect. There are very limited data from drug cases of serotonin syndrome have been reported. Therefore, while vaginitis including pseudomembranous patients with infections caused purely by Gram positive organisms (odds infestations candidiasis, fungal hypertension. interaction studies and on the safety of linezolid when administered to co-administration is contraindicated, management of patients for whom colitis* ratio 0.96; 95% confidence interval: 0.58-1.59) but were significantly † patients with underlying conditions and/or on concomitant medications treatment with linezolid and serotonergic agents is essential, is described infections In controlled clinical trials where linezolid was administered for up to 28 higher (p=0.0162) in the linezolid arm in patients with any other pathogen which might put them at risk from MAO inhibition. Therefore, linezolid is Blood and the lymphatic leucopenia*, neutropenia, myelosuppresion*, days, 2.0% of the patients reported anaemia. In a compassionate use or no pathogen at baseline (odds ratio 2.48; 95% confidence interval: in special warnings and precautions for use. anaemia*† pancytopenia* not recommended for use in these circumstances unless close system disorders thrombocytopenia*, sideroblastic anaemia* program of patients with life-threatening infections and underlying co- 1.38-4.46). The greatest imbalance occurred during treatment and within Use with tyramine-rich foods observation and monitoring of the recipient is possible. Immune system morbidities, the percentage of patients who developed anaemia when 7 days following discontinuation of study drug. More patients in the No significant pressor response was observed in subjects receiving both anaphylaxis linezolid arm acquired Gram negative pathogens during the study and Use with tyramine-rich foods linezolid and less than 100 mg tyramine. This suggests that it is only disorders receiving linezolid for ≤ 28 days was 2.5% (33/1326) as compared with Patients should be advised against consuming large amounts of tyramine necessary to avoid ingesting excessive amounts of food and beverages Metabolism and 12.3% (53/430) when treated for >28 days. The proportion of cases died from infection caused by Gram negative pathogens and polymicrobial hyponatraemia lactic acidosis* infections. Therefore, in complicated skin and soft tissue infections rich foods. with a high tyramine content (e.g. mature cheese, yeast extracts, nutrition disorders reporting drug-related serious anaemia and requiring blood transfusion linezolid should only be used in patients with known or possible co- Superinfection undistilled alcoholic beverages and fermented soya bean products such Psychiatric disorders insomnia was 9% (3/33) in patients treated for ≤ 28 days and 15% (8/53) in those The effects of linezolid therapy on normal flora have not been evaluated in as soy sauce). treated for >28 days. infection with Gram negative organisms if there are no alternative headache, taste clinical trials. Nervous system convulsions*, hypoaesthesia, serotonin syndrome**, treatment options available. In these circumstances treatment against Drugs metabolised by perversion (metallic Paediatric population Gram negative organisms must be initiated concomitantly. The use of antibiotics may occasionally result in an overgrowth of non- disorders paraesthesia peripheral neuropathy* Linezolid is not detectably metabolised by the cytochrome P450 (CYP) taste), dizziness Safety data from clinical studies based on more than 500 paediatric susceptible organisms. For example, approximately 3% of patients enzyme system and it does not inhibit any of the clinically significant Antibiotic-associated diarrhoea and colitis optic neuropathy*, optic patients (from birth to 17 years) do not indicate that the safety profile of receiving the recommended linezolid doses experienced drug-related human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Similarly, Antibiotic-associated diarrhoea and antibiotic-associated colitis, including neuritis*, loss of vision*, linezolid for paediatric patients differs from that for adult patients. pseudomembranous colitis and Clostridium difficile-associated diarrhoea, candidiasis during clinical trials. Should superinfection occur during linezolid does not induce P450 isoenzymes in rats. Therefore, no Eye disorders blurred vision* changes in visual field defect* changes in visual acuity*, Overdose has been reported in association with the use of nearly all antibiotics therapy, appropriate measures should be taken. CYP450-induced drug interactions are expected with linezolid. changes in colour vision* No specific antidote is known. including linezolid and may range in severity from mild diarrhoea to fatal Special populations Rifampicin No cases of overdose have been reported. However, the following colitis. Therefore, it is important to consider this diagnosis in patients who Linezolid should be used with special caution in patients with severe renal Ear and labyrinth The effect of rifampicin on the pharmacokinetics of linezolid was studied in tinnitus information may prove useful: develop serious diarrhoea during or after the use of linezolid. If insufficiency and only when the anticipated benefit is considered to sixteen healthy adult male volunteers administered linezolid 600 mg twice disorders antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected outweigh the theoretical risk. daily for 2.5 days with and without rifampicin 600 mg once daily for 8 Cardiac disorders arrhythmia (tachycardia) Supportive care is advised together with maintenance of glomerular or confirmed, ongoing treatment with antibacterial agents, including It is recommended that linezolid should be given to patients with severe days. Rifampicin decreased the linezolid Cmax and AUC by a mean 21% transient ischaemic attacks, filtration. Approximately 30% of a linezolid dose is removed during 3 hours Vascular disorders hypertension linezolid, should be discontinued and adequate therapeutic measures hepatic insufficiency only when the perceived benefit outweighs the [90% CI, 15, 27] and a mean 32% [90% CI, 27, 37], respectively. The phlebitis, thrombophlebitis of haemodialysis, but no data are available for the removal of linezolid by should be initiated immediately. Drugs inhibiting peristalsis are theoretical risk. mechanism of this interaction and its clinical significance are unknown. diarrhoea, nausea, peritoneal dialysis or haemoperfusion. contraindicated in this situation. , gastritis, abdominal Impairment of fertility Warfarin vomiting, localised or Instructions for use and handling Gastrointestinal distention, dry mouth, glossitis, Lactic acidosis Linezolid reversibly decreased fertility and induced abnormal sperm When warfarin was added to linezolid therapy at steady-state, there was a general abdominal superficial tooth discolouration For single use only. Remove overwrap only when ready to use, then morphology in adult male rats at exposure levels approximately equal to disorders loose stools, stomatitis, tongue Lactic acidosis has been reported with the use of linezolid. Patients who 10% reduction in mean maximum INR on co-administration with a 5% pain, constipation, check for minute leaks by squeezing the bag firmly. If the bag leaks, do those expected in humans; possible effects of linezolid on the human discolouration or disorder develop signs and symptoms of metabolic acidosis including recurrent reduction in AUC INR. There are insufficient data from patients who have dyspepsia not use as sterility may be impaired. The solution should be visually nausea or vomiting, abdominal pain, a low bicarbonate level, or male reproductive system are not known. received warfarin and linezolid to assess the clinical significance, if any, of abnormal liver function inspected prior to use and only clear solutions, without particles should be hyperventilation while receiving linezolid should receive immediate Clinical trials these findings. test; increased AST, used. Do not use these bags in series connections. Any unused solution medical attention. If lactic acidosis occurs, the benefits of continued use of The safety and effectiveness of linezolid when administered for periods Hepato-biliary disorders increased total bilirubin Fertility, pregnancy and lactation ALT or alkaline must be discarded. No special requirements for disposal. Any unused linezolid should be weighed against the potential risks. longer than 28 days have not been established. Pregnancy phosphatase medicinal product or waste material should be disposed of in accordance Mitochondrial dysfunction Controlled clinical trials did not include patients with lesions, There are no adequate data from the use of linezolid in pregnant women. bullous disorders such as with local requirements. Do not reconnect partially used bags. Linezolid inhibits mitochondrial synthesis. Adverse events, such as decubitus or ischaemic lesions, severe or gangrene. Therefore, Studies in animals have shown reproductive toxicity. A potential risk for those described as Stevens- Linezolid Solution for Infusion is compatible with the following solutions: lactic acidosis, anaemia and neuropathy (optic and peripheral), may occur experience in the use of linezolid in the treatment of these conditions is humans exists. Skin and subcutaneous as a result of this inhibition; these events are more common when the drug pruritus, rash urticaria, dermatitis, diaphoresis Johnson syndrome and 5 % glucose intravenous infusion, 0.9 % sodium chloride intravenous limited. Linezolid should not be used during pregnancy unless clearly necessary tissue disorders is used longer than 28 days. toxic epidermal necrolysis, infusion, Ringer-lactate solution for injection (Hartmann’s solution for Excipients i.e. only if the potential benefit outweighs the theoretical risk. Serotonin syndrome angioedema, alopecia injection). 300 ml of the solution contains 13.7 g glucose. This should be taken into Breast-feeding Spontaneous reports of serotonin syndrome associated with the Renal and urinary renal failure, increased Incompatibilities account in patients with diabetes mellitus. Animal data suggest that linezolid and its metabolites may pass into increased BUN co-administration of linezolid and serotonergic agents, including disorders creatinine, polyuria Additives should not be introduced into this solution. If linezolid is to be 300 ml of the solution also contains 114 mg sodium (5 mmol). The sodium breast milk and, accordingly, breastfeeding should be discontinued prior to antidepressants such as selective serotonin reuptake inhibitors (SSRIs) Reproductive system given concomitantly with other drugs, each drug should be given content should be taken into consideration by patients on a controlled and throughout administration. vulvovaginal disorder have been reported. Co-administration of linezolid and serotonergic sodium diet. and breast disorders separately in accordance with its own directions for use. Similarly, if the agents is therefore contraindicated except where administration of Fertility Interactions General disorders and same intravenous line is to be used for sequential infusion of several linezolid and concomitant serotonergic agents is essential. In those cases In animal studies, linezolid caused a reduction in fertility. chills, fatigue, injection site pain, Monoamine oxidase inhibitors administration site fever, localised pain drugs, the line should be flushed prior to and following linezolid patients should be closely observed for signs and symptoms of serotonin increased thirst Linezolid is a reversible, non-selective inhibitor of monoamine oxidase Effects on ability to drive and use machines conditions administration with a compatible infusion solution. syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and (MAOI). There are very limited data from studies and on Patients should be warned about the potential for dizziness or symptoms incoordination. If signs or symptoms occur physicians should consider Chemistry Linezolid Solution for Infusion is known to be physically incompatible with the safety of linezolid when administered to patients on concomitant of visual impairment whilst receiving linezolid and should be advised not discontinuing either one or both agents; if the concomitant serotonergic to drive or operate machinery if any of these symptoms occurs. Increased LDH, the following compounds: amphotericin B, chlorpromazine hydrochloride, medications that might put them at risk from MAO inhibition. Therefore, creatine kinase, lipase, diazepam, pentamidine isethionate, lactobionate, phenytoin agent is withdrawn, discontinuation symptoms can occur. Undesirable effects linezolid is not recommended for use in these circumstances unless close amylase or non fasting sodium and sulphamethoxazole / trimethoprim. Additionally, it is Peripheral and optic neuropathy observation and monitoring of the recipient is possible. The table below provides a listing of adverse drug reactions with Peripheral neuropathy, as well as optic neuropathy and optic neuritis glucose. Decreased chemically incompatible with ceftriaxone sodium. Potential interactions producing elevation of blood pressure frequency based on all-causality data from clinical studies that enrolled sometimes progressing to loss of vision, have been reported in patients total protein, albumin, Shelf life In normotensive healthy volunteers, linezolid enhanced the increases in more than 2,000 adult patients who received the recommended linezolid treated with linezolid; these reports have primarily been in patients treated sodium or calcium. 2 years blood pressure caused by pseudoephedrine and phenylpropanolamine doses for up to 28 days. Those most commonly reported were diarrhoea for longer than the maximum recommended duration of 28 days. Increased or Chemistry hydrochloride. Co-administration of linezolid with either pseudoephedrine (8.4%), headache (6.5%), nausea (6.3%) and vomiting (4.0%). After opening: Chemical and physical in-use stability has been All patients should be advised to report symptoms of visual impairment, decreased potassium Increased sodium or calcium. or phenylpropanolamine resulted in mean increases in systolic blood The most commonly reported drug-related adverse events which led to demonstrated for 24 hours at room temperature in primary bag after such as changes in visual acuity, changes in colour vision, blurred vision, or bicarbonate. Decreased non fasting glucose. pressure of the order of 30-40 mm Hg, compared with 11-15 mm Hg discontinuation of treatment were headache, diarrhoea, nausea and removal of the secondary pack (pouch). From a microbiological point of or visual field defect. In such cases, prompt evaluation is recommended Investigations Haematology Increased or decreased chloride. increases with linezolid alone, 14-18 mm Hg with either pseudoephedrine vomiting. About 3 % of patients discontinued treatment because they view, the product should be used immediately. If not used immediately, with referral to an ophthalmologist as necessary. If any patients are taking Increased neutrophils Haematology or phenylpropanolamine alone and 8-11 mm Hg with placebo. Similar experienced a drug-related adverse event. in-use storage times and conditions prior to use are the responsibility of linezolid for longer than the recommended 28 days, their visual function or eosinophils. Increased reticulocyte count. studies in hypertensive subjects have not been conducted. It is Additional adverse reactions reported from post-marketing experience are the user. should be regularly monitored. Decreased Decreased neutrophils. recommended that doses of drugs with a vasopressive action, including included in the table with frequency category ‘Not known’, since the actual Special precautions for storage If peripheral or optic neuropathy occurs, the continued use of linezolid haemoglobin, dopaminergic agents, should be carefully titrated to achieve the desired frequency cannot be estimated from the available data. Do not store above 30°C. should be weighed against the potential risks. haematocrit or red response when co-administered with linezolid. Store in the original package in order to protect from light. There may be an increased risk of neuropathies when linezolid is used in The following undesirable effects have been observed and reported during blood cell count. Potential serotonergic interactions patients currently taking or who have recently taken treatment with linezolid with the following frequencies: Very common Increased or The potential drug-drug interaction with dextromethorphan was studied in (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); medications for the treatment of tuberculosis. decreased platelet healthy volunteers. Subjects were administered dextromethorphan (two 20 rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); Not known (cannot be or white blood cell Convulsions mg doses given 4 hours apart) with or without linezolid. No serotonin estimated from the available data) Convulsions have been reported to occur in patients when treated with syndrome effects (confusion, delirium, restlessness, tremors, blushing, counts. diaphoresis, hyperpyrexia) have been observed in normal subjects