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Levofloxacin 5 mg/ml Solution for Infusion - UK - PIL Review - 2

i    Package leaflet: Information for the patient

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Levofloxacin 5 mg/ml Solution for Infusion

levofloxacin

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Read all of this leaflet carefully before you are given 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, nurse or pharmacist.

•    If you get any side effects talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet.

See section 4.

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What is in this leaflet

What Levofloxacin is and what it is used for What you need to know before you are given Levofloxacin 3. How Levofloxacin is given Possible side effects How to store Levofloxacin 6. Contents of the pack and other information

1.    What Levofloxacin solution for infusion is and what it is used for

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The name of your medicine is Levofloxacin solution for infusion (referred as “Levofloxacin” in this leaflet). The active ingredient in the solution is levofloxacin, which belongs to a group of medicines called antibiotics.

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Levofloxacin is a ‘quinolone' antibiotic. It works by killing the bacteria that cause infections in your body.

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Levofloxacin can be used to treat 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'.

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In some special situations, Levofloxacin may be used to lessen the chances of getting a pulmonary disease named anthrax or worsening of the disease after you are exposed to the bacteria causing anthrax.

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2.    What you need to know before you are given Levofloxacin

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Do not take Levofloxacin if:

•    you are allergic to levofloxacin, any other quinolone antibiotics such as moxifloxacin, ciprofloxacin or ofloxacin, or any of the other ingredients of this 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.

•    you have ever had epilepsy

•    you have ever had a problem with your tendons such as tendonitis that was related to treatment with a ‘quinolone antibiotic'. A tendon is the cord that joins your muscle to your skeleton

•    you are a child or a growing teenager

•    you are pregnant, might become pregnant, or think you may be pregnant

•    you are breast-feeding.

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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.

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Warnings and precautions

Talk to your doctor, nurse or pharmacist before you have your medicine if:

•    you are 60 years of age or older

•    you are using corticosteroids, sometimes called steroids (see section “Other medicines and Levofloxacin”)

•    you have ever had a fit (seizure)

•    you have had damage to your brain due to a stroke or other brain injury

•    you have kidney problems

•    you have something known as ‘glucose-6-phosphate dehydrogenase deficiency'. You are more likely to have serious problems with your blood when taking this medicine

•    you have ever had mental health problems

•    you have ever had heart problems: caution should be taken when using this kind of medicine, if you were born with or have a family history of prolonged QT interval (seen on ECG, electrical recording of the heart), have salt imbalance in the blood (especially low level of potassium or magnesium in the blood), have a very slow heart rhythm (called ‘bradycardia'), have a weak heart (heart failure), have a history of heart attack (myocardial infarcation), you are female or elderly or you are taking other medicines that result in abnormal ECG changes (see section “Other medicines and Levofloxacin”)

•    you are diabetic

•    you have ever had liver problems

•    you have myasthenia gravis (disease which causes muscle weakness)

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If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately.

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If you are not sure if any of the above applies to you, talk to your doctor, nurse or pharmacist before being given Levofloxacin.

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Other medicines and Levofloxacin

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Levofloxacin can affect the way some other medicines work. Also some medicines can affect the way Levofloxacin works.

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In particular, tell your doctor if you are taking any of the following medicines. This is because it can increase the chance of you getting side effects, when taken with Levofloxacin:

•    Corticosteroids, sometimes called steroids - used for inflammation. You may be more likely to have inflammation and/or rupture of your tendons.

•    Warfarin - used to thin the blood. You may be more likely to have

a bleed. Your doctor may need to take regular blood tests to check how well your blood can clot.

•    Theophylline - used for breathing problems. You are more likely to have a fit (seizure) if taken with Levofloxacin.

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The following information is intended for healthcare professionals only:

Incompatibilities

Levofloxacin 5 mg/ml solution for infusion should not be mixed with heparin or alkaline solutions (e.g. sodium hydrogen carbonate).

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This medicinal product must not be mixed with other medicinal products except those mentioned in the following section.

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Mixture with other solutions for infusion:

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Levofloxacin solution for infusion is compatible with the following solutions for infusion:

•    Sodium chloride solution 9 mg/ml (0.9%) solution.

•    Dextrose 50 mg/ml (5%) injection.

•    Dextrose 25 mg/ml (2.5%) in Ringer solution.

•    Combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

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Storage information

See section 5.

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Special precautions for disposal and other handling

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Levofloxacin solution for infusion should be used immediately (within 3 hours) after perforation of the rubber stopper in order to prevent any bacterial contamination. No protection from light is necessary during infusion. If not used immediately, in-use storage times and conditions are the responsibility of the user.

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This medicinal product is for single use only.

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The solution should be visually inspected prior to use. It must only be used if the solution is clear, greenish- yellow solution, practically free from particles.

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

•    Non-steroidal anti-inflammatory drugs (NSAIDS) - used for pain and inflammation such as aspirin, ibuprofen, fenbufen, ketoprofen, indomethacin. You are more likely to have a fit (seizure) if taken with Levofloxacin.

•    Ciclosporin - used after organ transplants. You may be more likely to get the side effects of ciclosporin.

•    Medicines known to affect the way your heart beats. This includes medicines used for abnormal heart rhythm (antiarrhythmics such as quinidine, hydroquinidine, disopyramide, sotalol, dofetilide, ibutilide and amiodarone), for depression (tricyclic antidepressants such as amitriptyline and imipramine), for psychiatric disorders (antipsychotics), and for bacterial infections (‘macrolide' antibiotics such as erythromycin, azithromycine and clarithromycin).

•    Probenecid - used for gout, and cimetidine - used for ulcers and heartburn. Special care should be taken when taking either of these medicines with Levofloxacin. If you have kidney problems, your doctor may want to give you a lower dose.

Urine tests for opiates

Urine tests may show ‘false-positive' results for strong painkillers called ‘opiates' in people having Levofloxacin. If your doctor has prescribed a urine test, tell your doctor you are having Levofloxacin.

Tuberculosis tests

This medicine may cause ‘false negative' results for some tests used in laboratory to search for the bacteria causing tuberculosis.

Pregnancy, breast-feeding and fertility

Do not have this medicine if:

•    You are pregnant, might become pregnant or think you may be pregnant

•    You are breast-feeding or planning to breast-feed.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Driving and using machines

You may get side effects after being given this medicine, including feeling dizzy, sleepy, a spinning feeling (vertigo) or changes to your eyesight. Some of these side effects can affect you being able to concentrate and your reaction speed. If this happens, do not drive or carry out any work that requires a high level of attention.

Levofloxacin contains sodium

This medicine contains sodium chloride (salt). The product contains 3.54 mg of sodium per ml of solution for infusion (a total of 354 mg sodium in 100 ml). This should be taken into consideration by patients on a controlled sodium diet.

3. How Levofloxacin is given

•    Levofloxacin 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 , the infusion time should be 30 minutes or more

•    For 500 mg Levofloxacin , 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 is given

If you are not sure why you are being given Levofloxacin or have any questions about how much Levofloxacin is being given to you, speak to your doctor, nurse or pharmacist.

•    Your doctor will decide on how much Levofloxacin 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.

Adults and elderly

•    Pneumonia: 500 mg once or twice daily

•    Infection of urinary tract, including your kidneys or bladder:

500 mg once daily

•    Prostate gland infection: 500 mg once daily

•    Infection of skin and underneath the skin, including muscles:

500 mg once or twice daily

Adults and elderly with kidney problems

Your doctor may need to give you a lower dose.

Children and adolescents

This medicine must not be given to children or teenagers.

Protect your skin from sunlight

Keep out of direct sunlight while having this medicine and for 2 days after you stop having it. This is because your skin will become much more sensitive to the sun and may burn, tingle or severely blister if you do not take the following precautions:

•    Make sure you use high factor sun cream

•    Always wear a hat and clothes which cover your arms and legs

•    Avoid sun beds

If you are given more Levofloxacin than you should

It is unlikely that your doctor or nurse will give you too much medicine Your doctor and nurse will monitor your progress, and check the medicine you are given. Always ask if you are not sure why you are getting a dose of medicine.

Having too much Levofloxacin may cause the following effects to happen: convulsive fits (seizures), feeling confused, dizzy, less conscious, having tremor and heart problems - leading to uneven heart beats as well as feeling sick (nausea).

If you miss a dose of Levofloxacin

Your doctor or nurse will have instructions on when to give you this medicine. It is unlikely that you will not be given the medicine as it has been prescribed. However, if you do think you have missed a dose, tell your doctor or nurse.

If you stop having Levofloxacin

Your doctor or nurse will continue giving you Levofloxacin, even if you feel better. If it is stopped too soon, your condition may get worse or the bacteria may become resistant to the medicine. After a few days treatment with the solution for infusion, your doctor may decide to switch you to the tablet form of this medicine to complete your course of treatment.

If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.

Posology

The following dose recommendations can be given for Levofloxacin:

Dosage in patients with normal renal function (creatinine clearance > 50 ml/min)

Indication	Daily dose regimen (according to severity)	Total duration of treatment1 (according to severity)
Community- acquired pneumonia	500 mg once or twice daily	7-14 days
Pyelonephritis	500 mg once daily	7-10 days
Complicated urinary tract infections	500 mg once daily	7-14 days
Chronic bacterial prostatitis	500 mg once daily	28 days
Complicated skin and soft tissue infections	500 mg once or twice daily	7-14 days
Inhalation anthrax	500 mg once daily	8 weeks

"'Treatment duration includes intravenous plus oral treatment. The time to switch from intravenous to oral treatment depends on the clinical situation but is normally 2 to 4 days.

Special populations

Impaired renal function (creatinine clearance <50ml/min)

Size : 210 x 720 mm, Colour: Q Black, Key line(Not to Print), Minimum Font size: 9.5 pt    Front Side

Date: 20/10/16

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are normally mild or moderate and often disappear after a short time.

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Stop having Levofloxacin and tell a doctor or nurse straight away if you notice the following side effect:

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Very rare (may affect up to 1 in 10,000 people):

• An allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat, or tongue.

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Stop having Levofloxacin and tell a doctor or nurse straight away if you notice any of the following serious side effects - you may need urgent medical treatment:

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Rare (may affect up to 1 in 1,000 people):

Watery diarrhoea which may have blood in it, possibly with stomach cramps and a high temperature. These could be signs of a severe bowel problem

Pain and inflammation in your tendons or ligaments which could lead to rupture. The Achilles tendon is affected most often.

Fits (convulsions).

Very rare (may affect up to 1 in 10,000 people):

Burning, tingling, pain or numbness. These may be signs of something called ‘neuropathy'.

Other:

Severe skin rashes which may include blistering or peeling of the skin around your lips, eyes, mouth, nose and genitals.

Loss of appetite, skin and eyes becoming yellow in colour, dark-coloured urine, itching, or tender stomach (abdomen). These may be signs of liver problems which may include a fatal failure of the liver.

Tell your doctor if any of the following side effects gets serious or lasts longer than a few days:

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Common (may affect up to 1 in 10 people):

Sleeping problems Headache, feeling dizzy Feeling sick (nausea, vomiting) and diarrhoea Increase in the level of some liver enzymes in your blood Reactions at the site of infusion Inflammation of a vein

Uncommon (may affect up to 1 in 100 people):

Changes in the number of other bacteria or fungi, infection by fungi named Candida, which may need to be treated Changes in the number of white blood cells shown up in the results of some blood tests (leukopenia, eosinophilia)

Feeling stressed (anxiety), feeing confused, feeling nervous, feeling sleepy, trembling, a spinning feeling (vertigo)

Shortness of breath (dyspnoea)

Changes in the way things taste, loss of appetite, stomach upset or indigestion (dyspepsia), pain in your stomach area, feeling bloated (flatulence) or constipation

Itching and skin rash, severe itching or hives (urticaria), sweating too much (hyperhidrosis)

Joint pain or muscle pain

Blood tests may show unusual results due to liver (bilirubin increased) or kidney (creatinine increased) problems General weakness

Rare (may affect up to 1 in 1,000 people):

Bruising and bleeding easily due to a lowering in the number of blood platelets (thrombocytopenia)

Low number of white blood cells (neutropenia)

Exaggerated immune response (hypersensitivity)

Lowering of your blood sugar levels (hypoglycaemia). This is important for people that have diabetes Seeing or hearing things that are not there (hallucinations, paranoia), change in your opinion and thoughts (psychotic reactions) with a risk of having suicidal thoughts or actions Feeling depressed, mental problems, feeling restless (agitation), abnormal dreams or nightmares Tingly feeling in your hands and feet (paraesthesia)

Problems with your hearing (tinnitus) or eyesight (blurred vision) Unusual fast beating of your heart (tachycardia) or low blood pressure (hypotension)

Muscle weakness. This is important in people with myasthenia gravis (a rare disease of the nervous system)

Changes in the way your kidney works and occasional kidney failure which may be due to an allergic kidney reaction called interstitial nephritis Fever

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse.

This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, website - www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5.    How to store Levofloxacin

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

Do not use this medicine after the expiry date which is stated on the bag and carton. The expiry date refers to the last day of that month.

Do not store above 30 °C.

Keep the bag in the outer carton in order to protect from light.

Once the infusion bag has been opened the solution should be used immediately in order to prevent any bacterial contamination.

Make a visual inspection before use. Only particle free clear solutions should be used.

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

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

6.    Contents of the pack and other information

What Levofloxacin contains:

•    The active substance is levofloxacin (as levofloxacin hemihydrate). Each ml of solution for infusion contains 5 mg of levofloxacin.

Each 100 ml bag of solution for infusion contains 500 mg of levofloxacin.

•    The other ingredients are sodium chloride, hydrochloric acid 1N or sodium hydroxide 1N (for pH adjustment (qs: pH 4.5 to 5) and water for injections.

What Levofloxacin looks like and contents of the pack:

Levofloxacin 5 mg/ml solution for infusion is a clear, greenish-yellow solution, free from visible particles.

Levofloxacin is presented in bags for infusion with 100 ml volume. Packs of 20 bags.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Amneal Pharma Europe Ltd 70 Sir John Rogerson's Quay Dublin 2, Ireland

Manufacturer

LABORATORIOS Normon, S.A.

Ronda de Valdecarrizo, 6 - 28760 Tres Cantos - Madrid (SPAIN)

This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.

This leaflet was last revised in: October 2016

Lowering in red blood cells (anemia): this can make the skin pale or yellow due to damage of the red blood cells; lowering in the number of all types of blood cells (pancytopenia)

Fever, sore throat and a general feeling of being unwell that does not go away. This may be due to a lowering in the number of white blood cells (agranulocytosis)

Loss of circulation (anaphylactic like shock)

Increase of your blood sugar levels (hyperglycaemia) or lowering of your blood sugar levels leading to coma (hypoglycaemic coma). This is important for people that have diabetes.

Changes in the way things smell, loss of smell or taste (parosmia, anosmia, ageusia)

Problems moving and walking (dyskinesia, extrapyramidal disorders) Temporary loss of consciousness or posture (syncope)

Temporary loss of vision Impairment or loss of hearing

Abnormal fast heart rhythm, life-threatening irregular heart rhythm including cardiac arrest, alteration of the heart rhythm (called ‘prolongation of QT interval', seen on ECG, electrical activity of the heart)

Difficulty breathing or wheezing (bronchospasm)

Allergic lung reactions Pancreatitis

Inflammation of the liver (hepatitis)

Increased sensitivity of your skin to sun and ultraviolet light (photosensitivity)

Inflammation of the vessels that carry blood around your body due to an allergic reaction (vasculitis)

Inflammation of the tissue inside the mouth (stomatitis)

Muscle rupture and muscle destruction (rhabdomyolysis)

Joint redness and swelling (arthritis)

Pain, including pain in the back, chest and extremities Attacks of porphyria in people who already have porphyria (a very rare metabolic disease)

Persistent headache with or without blurred vision (benign intracranial hypertension)

No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Impaired liver function

No adjustment of dose is required since levofloxacin is not metabolised to any relevant extent by the liver and is mainly excreted by the kidneys.

Elderly

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No adjustment of dose is required in the elderly, other than that imposed by consideration of renal function (see section 2).

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Paediatric Population

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Levofloxacin is contraindicated in children or growing adults.

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Size : 210 x 720 mm, Colour: Q Black, Key line(Not to Print), Minimum Font size: 9.5 pt    Back Side

Date: 20/10/16