LEVOFLOXACIN 5 MG/ML SOLUTION FOR INFUSION

Package leaflet: Information for the patient Levofloxacin 5 mg/ml Solution for infusion Levofloxacin 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. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet 1. What Levofloxacin Solution for infusion is and what it is used for 2. Before you are given Levofloxacin Solution for infusion 3. How you will be given Levofloxacin Solution for infusion 4. Possible side effects 5. How to store Levofloxacin Solution for infusion 6. Contents of the pack and other information 1. What Levofloxacin Solution for infusion is and what it is used for The active ingredient in the solution is levofloxacin. Levofloxacin belongs to a group of medicines known as fluoroquinolone antibiotics, which kill bacteria. Levofloxacin Solution for infusion is used to treat infections caused by sensitive bacteria. Your doctor will have decided if your infection can be treated with this medicine. Some infections, which the solution can be used to treat, are infections of the: lungs, in people with pneumonia. urinary tract, including your kidneys or bladder. prostate gland, where you have a long lasting infection. skin and underneath the skin, including muscles. This is sometimes called soft tissue.

2. Before you are given Levofloxacin Solution for infusion Do not have this medicine and tell your doctor if you are allergic (hypersensitive) to levofloxacin, any other quinolone antibiotic such as moxifloxacin, ciprofloxacin or ofloxacin or to any of the other ingredients of the medicine (listed in section 6). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. have ever had epilepsy. Otherwise, your risk of getting fits (convulsions) is increased. had ever had tendon problems (e.g. tendonitis) related to treatment with a drug that belongs to the same class of antibiotics (i.e. fluoroquinolones). are pregnant, might become pregnant, or think you may be pregnant. are breast-feeding. are a child or growing teenager up to 18 years of age. It could harm the cartilage of the growing bones. The solution is only intended for adults. Do not have this medicine if any of the above applies to you. If you are not sure, talk to your doctor, nurse or pharmacist before you are given Levofloxacin Solution for infusion. Tell your doctor if you have had any problems with taking medicines in the past. Take special care with Levofloxacin Solution for infusion if you are 65 years of age or older. if you are using corticosteroids, sometimes called steroids (see Taking other medicines). if you have experienced fits or brain damage in the past (such as stroke or severe brain injury). Make sure your doctor knows about your medical history, so he can give you appropriate advice. when you are exposed to sunlight or UV light. Do not stay out in strong sunlight for unnecessarily long periods and do not use a sun-lamp or solarium. Your skin may become more sensitive to light while using this medicine (may cause sunburnlike reactions). if you get pain or inflammation in your tendons. If you experience any tendon complaints during or shortly after receiving this medicine you should seek medical advice immediately and rest the affected limb to avoid tendon damage. Do not take the next dose unless your doctor tells you to. if you have severe, persistent and/or bloody diarrhoea during or after treatment with this medicine. This may be a sign of serious bowel inflammation (pseudomembranous colitis) which can occur following treatment with antibiotics. Tell your doctor immediately. It may be necessary to stop treatment and start specific therapy. if you have a family history of or have an actual defect in the liver enzyme called glucose- 6-phosphate dehydrogenase (G6PD) (a rare hereditary disease). Patients with G6PD deficiency may be prone to destruction of red blood cells (haemolysis) when treated with quinolone antibacterial agents.

if you suffer from kidney problems. Patients with reduced kidney activity (renal insufficiency) may need lower doses than patients with normal kidney activity. if you are taking any drugs which thin the blood (known as anticoagulants e.g. warfarin). if you have a history of psychiatric disease or mental health problems. Tell your doctor immediately if you experience a psychotic reaction. if you are diabetic. if you have ever had heart problems. if you were born with or have family history of prolonged QT interval (seen on ECG, electrical recording of the heart). if you have salt imbalance in the blood (especially low level of potassium or magnesium in the blood) if you have a very slow heart rhythm (called bradycardia). if you have a weak heart (heart failure). if you have a history of heart attack (myocardial infarction). if you are female or elderly or you are taking other medicines that result in abnormal ECG changes (see section Taking other medicines). if you have ever had liver problems. If you are not sure if any of the above applies to you, talk to your doctor, nurse or pharmacist before being given Levofloxacin Solution for infusion. Taking other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Some medicines can interfere with your treatment or alter blood levels of those drugs you are currently taking, so make sure to check with your doctor or pharmacist before taking any other medications whether prescribed by a doctor or bought by you over the counter. In particular tell your doctor if you are taking any of the following: Vitamin K antagonists such as warfarin in combination with Levofloxacin Solution for infusion may lead to an increase in bleeding. Non-steroidal anti-inflammatory drugs (NSAIDs) used for pain and inflammation, such as acetylsalicylic acid, ibuprofen, fenbufen, ketoprofen and indomethacin. The risk of getting a fit (seizure) may be increased. Theophylline used for breathing problems. The risk of getting a fit (seizure) may be increased. Probenecid (used to prevent gout) or cimetidine (used to treat ulcers) reduce your kidneys ability to get rid of levofloxacin. Ciclosporin (used to treat psoriasis, dermatitis, rheumatism or after organ transplants). The effect of ciclosporin may be prolonged if used in combination with Levofloxacin Solution for infusion. You may also be more likely to get the side effects of ciclosporin. Corticosteroids, sometimes called steroids. You may be more likely to have inflammation and/or breakage of your tendons. Medicines known to affect the way your heart beats. This includes medicines used for abnormal heart rhythm (anti-arrhythmics such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide and ibutilide ), for depression (tricyclic

antidepressants such as amitriptyline and imipramine), for bacterial infections (macrolide antibiotics such as erythromycin, azithromycine and clarithromycin) and some antipscyhotics. Urine tests for opiates Urine tests may show false-positive results for strong painkillers called opiates in people taking Levofloxacin Solution for infusion. If your doctor is due to take a urine test, tell him you are having Levofloxacin Solution for infusion. Pregnancy and Breast-feeding Do not have Levofloxacin Solution for infusion if you are pregnant, might become pregnant or think you might be pregnant. are breast-feeding a baby or planning to breastfeed. It could harm your baby. Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breastfeeding. Driving and using machines Some side-effects like dizziness, drowsiness and visual disturbances may impair your ability to concentrate and react. Do not drive, operate dangerous machinery or have similar activities if you feel that your ability to concentrate and react is impaired. Important information about some of the ingredients of Levofloxacin Solution for infusion Levofloxacin Solution for infusion contains approximately 354 mg of sodium per maximum dose of 500 mg levofloxacin. This should be taken into consideration by patients on a controlled sodium diet and in cases where fluid restriction is required. 3. How Levofloxacin Solution for infusion is given to you Levofloxacin Solution for infusion is a medicine for use in hospitals. It will be given to you by a doctor or nurse as an injection. The injection will be into one of your veins and be given over a period of time (this is called an intravenous infusion). For 250 mg Levofloxacin Solution for infusion, the infusion time should be 30 minutes or more. For 500 mg Levofloxacin Solution for infusion, the infusion time should be 60 minutes or more. Your heart rate and blood pressure should be closely monitored. This is because an unusual fast beating of the heart and a temporary lowering of blood pressure are possible side effects that have been seen during the infusion of a similar antibiotic. If your blood pressure drops noticeably while you are being given the infusion, it will be stopped straight away. How much Levofloxacin Solution for infusion is given Your doctor will decide on how much Levofloxacin Solution for infusion you should have. The dose will depend on the type of infection you have and where the infection is

in your body. The length of your treatment will depend on how serious your infection is. The usual doses are given below. Adults and the elderly: Pneumonia: 500mg once or twice daily. Urinary tract, including your kidneys or bladder: 250mg once daily (the dose can be increased in cases of severe infection). Prostate gland: 500mg once daily. Skin and underneath the skin, including muscles: 500mg twice daily. Adults with kidney problems: Your doctor may need to give you a lower dose. Children and Teenagers: This medicine must not be given to children or teenagers up to 18 years of age. If you have more Levofloxacin Solution for infusion than you should Your doctor or nurse will ensure that you will receive the correct dose into the vein. Symptoms of an accidental overdose might result in central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and (convulsive) fits and heart disorders, possibly leading to abnormal heart rhythm. Consult your doctor if you think you have been administered more Levofloxacin Solution for infusion than you should. If you miss a dose of Levofloxacin Solution for infusion If you think that you may have missed a dose talk to your doctor or nurse. You should not have a double dose to make up for a forgotten dose. If you stop having Levofloxacin Solution for infusion Your doctor may decide to stop treatment into a vein and ask you to continue treatment with Levofloxacin Tablets. If you still feel unwell at the end of your prescribed course of treatment, tell your doctor. If you have any further questions on the use of this product, ask your doctor. 4. Possible side effects Like all other medicines Levofloxacin Solution for infusion can cause side effects although not everybody gets them. Severe allergic reaction is a very rare side effect of Levofloxacin Solution for infusion. The signs may include a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. If you experience any of these signs, tell your doctor or nursing staff immediately. The following side effects have been observed with use of this medicine, arranged according to frequency: Common side effects (affects 1 to 10 users in 100): Feeling sick (nausea), diarrhoea Increase in blood levels of liver enzymes

Reactions at the site of infusion Inflammation of a vein. Uncommon side effects (affects 1 to 10 users in 1,000): Itching and rash Loss of appetite, stomach upset or indigestion (dyspepsia), vomiting or pain in the stomach area, feeling bloated (flatulence), constipation Headache, dizziness, a spinning feeling (vertigo), drowsiness, sleeping problems, nervousness Increase or decrease in the number of white blood cells Blood tests may show unusual results due to liver or kidney problems General weakness. Any antibacterial treatment that kills certain germs may lead to a disturbance of the micro-organisms (bacteria/ fungi) that are normally found in humans. Consequently, the number of other bacteria or fungi may increase, which in rare cases requires treatment. Rare side effects (affects 1 to 10 users in 10,000): Bloody diarrhoea which in very rare cases may be indicative of enterocolitis (inflammation of the bowel), including pseudomembranous colitis (inflammation of the large intestine) Feeling a tingling sensation, e.g. in the hands (paraesthesia), trembling, fits (convulsions) and confusion Anxiety, depression, psychotic reactions, restlessness (agitation) Abnormally rapid beating of the heart, abnormally low blood pressure Tendon pain and inflammation (tendonitis), joint pain or muscle pain Decrease in the number of blood platelets leading to tendency to bruise and bleed easily, low number of white blood cells (called neutropenia) Difficulty breathing or wheezing (bronchospasm) Shortness of breath (dyspnoea) Severe itching, hives (called urticaria). Very rare side effects (affects less than 1 user in 10,000): Severe allergic reaction. The signs may include a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue Sudden drop in blood pressure or collapse (shock), increased sensitivity of the skin to sun and ultraviolet light Decrease in blood sugar to a too low level (hypoglycaemia) which may be of special importance in patients treated for diabetes Vision and hearing disorders, disturbances of taste and smell Burning, tingling, pain or numbness. These may be signs of something called neuropathy Hallucinations, psychotic reactions with risk of suicidal thoughts or actions Circulatory collapse (anaphylactic like shock) Tendon rupture (e.g. Achilles tendon), which may occur within 48 hours after starting treatment and may be bilateral, muscular weakness, which may be of special importance in patients with myasthenia gravis (a rare disease of the nervous system)

Severe decrease in the number of white blood cells (agranulocytosis) leading to symptoms such as recurrence or persistence of fever, sore throat and feeling more ill again Inflammation of the liver, disturbances of kidney function and occasional kidney failure due to allergic kidney reactions (interstitial nephritis) Fever Allergic lung reactions. Not known (frequency cannot be estimated from the available data): Severe blistering reactions of the skin and mucous membranes (Stevens Johnson syndrome), toxic epidermal necrolysis (Lyells syndrome) and erythema exsudativum multiforme. Muco-cutaneous (e.g. hives or flushing) may sometimes occur even after the first dose Heart disorders Abnormal fast heart rhythm Life-threatening irregular heart rhythm Alteration of the heart rhythm (called prolongation of QT interval, seen on ECG, electrical activity of the heart) Muscle reactions with muscle cell damage (rhabdomyolysis) Decrease in red blood cells (anaemia) due to blood cell damage, decrease in the number of all types of blood cells Yellowing of the skin or whites of the eyes (jaundice) Severe liver injury, including cases with acute liver failure, have been reported with levofloxacin, primarily in patients with severe underlying diseases Sweating too much (hyperhidrosis) Pain, including pain in the back, chest and extremities Ringing or buzzing in the ears (tinnitus) Exaggerated immune response (hypersensitivity). Other undesirable effects which have been associated with fluoroquinolone administration include: Extrapyramidal (neurological) symptoms and other disorders of muscular coordination Hypersensitivity vasculitis (inflammation of small blood vessels) Attacks of porphyria in patients with porphyria (a very rare metabolic disease). If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell you doctor or your pharmacist. 5. How to store Levofloxacin Solution for infusion Keep out of the sight and reach of children. Do not use this medicine after the expiry date shown on the labelling as EXP. The expiry date refers to the last day of that month. Do not freeze.

Keep bottle/bag in the outer carton/over wrap pouch in order to protect from light and remove only immediately prior to use. No protection from light is required during infusion. Once the infusion has been opened (rubber stopper perforated) the solution should be used immediately (within 3 hours) in order to prevent any bacterial contamination. Only clear solutions practically free from particles should be used. Do not use if container is damaged. Discard any unused solution. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. 6. Contents of the pack and other information What Levofloxacin Solution for infusion contains The active substance ingredient is levofloxacin (as levofloxacin hemihydrate). Each ml of solution for infusion contains 5 mg of levofloxacin. Each 100 ml of solution for infusion contains 500 mg of levofloxacin. The other ingredients are sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injections What Levofloxacin Solution for infusion looks like and the contents of the pack: Levofloxacin 5 mg/ml Solution for infusion is a clear, yellow to greenish-yellow solution. The solution is available in a 100 ml glass bottle closed with a rubber stopper and flip off seal and in 100 ml Non PVC bag. The 100 ml bottles are available in packs of 1, 5 and 10. The 100 ml bags are available in packs of 1, 5 and 10. Not all pack sizes may be marketed. Marketing Authorization Holder
Pfizer Limited Ramsgate Road Sandwich Kent CT13 9NJ United Kingdom

Pfizer Service Company BVBA Hoge Wei 10-B-1930 Zaventem Belgium

Manufacturer

This leaflet was last revised in 07/2012. <--------------------------------------------------------------------------------------------------------- Levofloxacin 5 mg/ml Solution for infusion Method of Administration This medicine is intended exclusively for the slow intravenous infusion once or twice daily. Duration of Treatment The infusion time must be at least 30 minutes for 250 mg or 60 minutes for 500 mg Levofloxacin Solution for infusion. The following dose recommendations can be given for Levofloxacin Solution for infusion: Dosage in patients with normal renal function (creatinine clearance > 50 ml/min) Indication Community acquired pneumonia Complicated urinary tract infections including pyelonephritis Chronic bacterial prostatitis Skin and soft tissue infections Daily dose schema (according to severity) 500 mg once or twice a day 250 mg once a day* 500 mg once daily 500 mg twice daily

*Consideration should be given to increasing the dose in cases of severe infection and special attention should be paid to available information on resistance to levofloxacin before commencing therapy. Because of the increasing E.coli resistance the dose 500 mg/day should be considered. Dosage in patients with impaired renal function (creatinine-clearance 50 ml / min) Dose regimen 250 mg/24 h 500 mg/24 h 500 mg/12 h first dose: 250 mg first dose: 500 mg first dose: 500 mg Creatinine clearance 50 - 20 ml/min then: 125 mg/24 h then: 250 mg/24 h then : 250 mg/12 h 19 - 10 ml/min then: 125 mg/48 h then: 125 mg/24 h then: 125 mg/12 h < 10 ml/mi then: 125 mg/48 h then: 125 mg/24 h then: 125 mg/24 h

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(including haemodialysis and CAPD) 1 1 No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). For further information, see section 3 How you will be given Levofloxacin Solution for infusion Mixture with other solutions for infusion This medicine is compatible with the following solutions for infusion: 0.9 % sodium chloride solution USP 5 % dextrose injection USP 2.5 % dextrose in Ringer solution Combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes). Incompatibilities Levofloxacin Solution for infusion should not be mixed with heparin or alkaline solutions (e.g. sodium hydrogen carbonate). Special precautions for the disposal and other handling From a microbiological point of view, the solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user (refer to section 5 How to store Levofloxacin Solution for infusion). As for all medicines, any unused medicinal product should be disposed of accordingly and in compliance with local environmental regulations. Information about storage See section 5 "How to store Levofloxacin Solution for infusion".