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PACKAGE LEAFLET: INFORMATION FOR THE USER

Levofloxacin 5 mg/ml solution for infusion

levofloxacin

Read all of this leaflet carefully before you start

using this medicine.

•    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 any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

1.    What Levofloxacin 5 mg/ml is and what it is used for

2.    Before you are given Levofloxacin 5 mg/ml

3.    How Levofloxacin 5 mg/ml is given

4.    Possible side effects

5.    Storing Levofloxacin 5 mg/ml

6.    Further information

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1. What Levofloxacin 5 mg/ml is and what it is used for

Levofloxacin belongs to a group of antibiotics called fluorquinolones. It works by stopping the growth of bacteria that cause infections.

Levofloxacin is used to treat the following bacterial infections:

•    pneumonia,

•    complicated (difficult to treat) urinary tract infections including infection of the kidney (pyelonephritis),

•    infections of the skin and underneath the skin, including muscles. This is sometimes called “soft tissue infections”.

•    infection of the prostate.

2. Before you use Levofloxacin 5 mg/ml

Do not use Levofloxacin 5mg/ml and tell your

doctor:

•    if your are allergic (hypersensitive) to levofloxacin or any of the ingredients of Levofloxacin 5 mg/ml solution for infusion, or if you have ever had an allergic reaction to any other quinolone antibiotic. See section 6 of this leaflet for a list of ingredients.

•    if you suffer from epilepsy, because your risk of getting “fits” (convulsions) is increased.

•    if you have ever had tendon problems (e.g. tendinitis) related to treatment with an antibiotic of the fluoroquinolone class. This is because there is a risk of having similar problems with levofloxacin, including tendon rupture.

•    if you are pregnant or breast-feeding a baby. Levofloxacin 5 mg/ml could harm your baby. (See also “Pregnancy and lactation”).

•    The medicine is only for use in adults and must not be given to children or growing teenagers. It could harm the cartilage of their growing bones.

Take special care with Levofloxacin 5 mg/ml:

•    Before treatment with Levofloxacin 5 mg/ml tell your doctor if, in the past, you have experienced brain damage such as stroke or severe brain injury because the risk of getting fits may be increased.

•    The risk of getting fits may also be increased if you take this medicine with other drugs such as fenbufen or similar medicines for rheumatic pain and inflammation or with theophylline (a medicine used to treat asthma). (see also “Using other medicines”). Make sure your doctor knows about your medical history, so he can give you appropriate advice.

•    Do not stay out in strong sunlight for unnecessarily long periods and do not use a sun-lamp or solarium while you are taking Levofloxacin 5 mg/ml. This is because you may become more sensitive to light while receiving the infusion (sunburn-like reactions).

•    If, during your treatment or even weeks after treatment has stopped, you get severe diarrhoea, that may contain blood or mucus and does not go away, tell your doctor immediately. This could be a sign of a serious bowel condition (pseudomembranous colitis) and it may be necessary to stop treatment with Levofloxacin 5 mg/ml and start treating this condition.

•    Levofloxacin 5 mg/ml may, in rare cases, cause tendinitis (pain and swelling or redness around your tendon), particularly if you are elderly or if you are taking corticosteroids (cortisone and similar medicines). If you have any tendon complaints tell your doctor immediately and rest the affected limb to avoid tendon damage. It may be necessary to stop treatment (see “Do not use Levofloxacin 5 mg/ml”).

•    Tell your doctor if you have an abnormality of an enzyme called glucose-6-phosphate dehydrogenase (G6-PD) (a rare hereditary disease). This condition causes a deficiency of certain chemicals in the red blood cells and if you are given levofloxacin, it may lead to the break down of red blood cells resulting in anaemia and yellowing of the skin (jaundice).

•    Tell your doctor if you have had a psychiatric disease as you may have thoughts of suicide or of harming yourself when you are on levofloxacin. If this happens your treatment will be stopped immediately.

•    If you have kidney problems your doctor may have to adjust the dose of this medicine (see also section 3, “How to use Levofloxacin 5 mg/ml”).

•    Tell you doctor or nurse if you are taking a blood thinner such as Warfarin as taking these two medicines together can increase the risk bleeding problems. (See also “Using other medicines”).

•    Levofloxacin has been known to cause serious allergic reactions, even during or after the first dose. If you develop hives or a skin rash, difficulty in breathing, or other symptoms of an allergic reaction (see also section 4 “Possible side effects”), tell your doctor or nurse immediately.

•    Tell your doctor or nurse if you are diabetic and are taking insulin or a hypoglycaemic agent, you may have a hypoglycaemic reaction while on Levofloxacin 5mg/ml. Your doctor will carefully monitor your blood glucose level

•    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 levels of potassium or magnesium), have a very slow heart rhythm (called “bradycardia”), have a weak heart (heart failure), have a history of heart attack (myocardial infarctation), you are female or elderly or you are taking other medicines that result in abnormal ECG changes (see section “Taking other medicines”). Tell you doctor or nurse if you have changes in the way your heart beats or if you experience fainting spells.

•    If you experience weakness, tingling or numbness of arms and legs or face tell you doctor or nurse immediately as treatment may have to be stopped.

•    Levofloxacin may produce false positive urine screening results for opiates (narcotic drugs). Tell your doctor if you are having tests done.

•    Levofloxacin has been known to cause effects on the liver which may rarely progress to liver failure, mainly in patients with underlying disease. Contact your doctor right away if you have unexplained symptoms such as loss of appetite, yellowing of your skin or white of your eyes, dark coloured urine, itching or abdominal pain or tenderness.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Levofloxacin can affect the way some other medicines work. Also some medicines can affect the way Levofloxacin works.

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;

•    Fenbufen or similar medicines for rheumatic pain and swelling, or theophylline (a medicine used for respiratory diseases such as asthma). This is because the risk of getting fits may be increased if you take Levofloxacin 5 mg/ml with these medicines.

•    Probenecid (for arthritis) or cimetidine (for stomach ulcer and heartburn) because they reduce your kidneys' ability to get rid of your medicine.

•    Ciclosporin (a medicine to reduce the activity of the immune system after organ transplants for example). Levofloxacin 5 mg/ml may prolong the effect of this medicine.

•    Medicines to thin your blood, such as warfarin

•    Medicines that can alter your heart rhythm: Medicines that belong to the group of anti-arrhythmics (such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (that belong to the group of macrolides), some antipsychotics.

Pregnancy and breastfeeding

You must not use Levofloxacin 5 mg/ml if your are pregnant or think that you may be pregnant, or if you are breastfeeding, as it could harm your baby. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

This medication may make you feel dizzy or drowsy and could affect your sight (see also “Possible side effects”) which lowers your ability to concentrate and react. Do not drive, operate dangerous machinery or carry out similar activities if you feel that your ability to concentrate and react is lowered.

Important information about some of the ingredients of Levofloxacin 5 mg/ml

This medicinal product contains sodium chloride (salt). The product contains 3.5 mg of sodium per ml of infusion (a total of 177.1 mg sodium in 50 ml and 354.2 mg sodium in 100 ml). If you are on a low sodium (salt) diet tell your doctor or nurse before they give you Levofloxacin Infusion

3. How to use Levofloxacin 5mg/ml

The dose of levofloxacin will depend on the type and severity of the infection.

Your doctor or nurse will administer each dose by slow injection (infusion) through a vein, once or twice daily. A bag containing 250 mg (50 ml) should be infused for at least 30 minutes and a bag containing 500 mg (100 ml) should be infused for least 60 minutes.

Detailed instructions for your doctor or nurse on how to prepare and administer this medicine are given at the end of this leaflet, see “Handling instructions”.

Dosage;

Patients with normal kidney function (creatinine clearance > 50 ml/min)

•    Pneumonia

One infusion of Levofloxacin 500 mg, once or twice each day

•    Infection of the prostate

One infusion of Levofloxacin 500 mg, once each day.

Handling instructions

Preparation for administration:

1.    Inspect the bag before use. It must only be used if the solution is a clear, greenish- yellow solution, practically free from particles.

2.    Hold the plastic bag with the connection ports uppermost.

3.    Twist off the protection cap from the connection port

4.    Insert the piercing pin of the i.v. set into the connection port with a twisting motion.

5.    Suspend the bag from the hanger

See the carton box of the product for diagram

Method of administration

The solution for infusion is ready for use, and should only be administered by slow infusion into a vein. The infusion time should not be less than 30 minutes for 250 mg (50 ml) and not be less than 60 minutes (1 hour) for 500 mg (100 ml) of levofloxacin solution for infusion. Protection from light is not necessary during infusion time.

Special warnings and precautions for use:

Infusion Time

The recommended infusion time of at least 30 minutes for 250 mg or 60 minutes for 500 mg Levofloxacin 5 mg/ml solution for infusion should be observed. It is known for ofloxacin, that during infusion tachycardia and a temporary decrease in blood pressure may develop. In rare cases, as a consequence of a profound drop in blood pressure, circulatory collapse may occur. Should a conspicuous drop in blood pressure occur during infusion of levofloxacin, (L-isomer of ofloxacin) the infusion must be halted immediately.

Dosage in patients with kidney impairment

	250 mg/24 h	500 mg/24 h	500 mg/12 h
Creatinine clearance	first dose 250 mg	first dose 500 mg	first dose 500 mg
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

•    Complicated (difficult to treat) urinary tract infections including infection of the kidney

One infusion of Levofloxacin 250 mg, once each day

•    Infections of the skin and underneath the skin, including muscles

One infusion of Levofloxacin 500 mg, twice each day.

Patients with kidney problems

If your kidney function is below normal your doctor will adjust the dose of Levofloxacin depending on your degree of kidney impairment, as you will need lower doses than patients with normal kidney function.

The dosage for patients with kidney problems is given at the end of this leaflet, see “Handling instructions”.

Elderly patients (with normal kidney function)

The dose does not need to be adjusted

Patients with impaired liver function

The dose does not need to be adjusted

Duration of treatment

The duration of treatment will depend on your clinical condition the severity of your illness and how you respond to treatment. Treatment with Levofloxacin 5 mg/ml should be continued for at least 2 to 3 days after your body temperature has returned to normal and your symptoms have lessened.

Once your condition has improved, the way your treatment is given may be changed from an infusion into a vein to tablets given orally at the same daily dose.

If you are given more Levofloxacin 5 mg/ml than you should be.

Your doctor or nurse will ensure that you receive the correct dose. If you are accidentally given an overdose you may have symptoms such as confusion, dizziness, loss of consciousness and fits and abnormal heart beat. Treatment is according to symptoms. Levofloxacin is not removed from the body by dialysis. No specific antidote exists.

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

4. Possible side effects

Like all medicines, Levofloxacin 5 mg/ml can cause side effects, although not everybody gets them.

Serious side effects

Tell your doctor or nurse straight away

if you have any of the following symptoms of a severe allergic reaction:

•    swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing

•    extreme dizziness or collapse

•    severe or itchy skin rash, especially if this shows blistering of the skin and/or inside of the lips, eyes, mouth, nasal passages or genitals

These are serious side effects. You may need urgent medical attention. They are very rare (affects less than 1 user in 10,000 people) and may sometimes occur with the first dose during or after infusion.

Other possible side effects

Common side effects (affects 1 to 10 users in 100)

•    nausea, diarrhoea

•    increase in blood levels of liver enzymes

•    pain, reddening and swelling of the blood vessels at the injection site

Uncommon side effects (affects 1 to 10 users in 1,000):

•    loss of appetite

•    indigestion, vomiting, abdominal pain, wind, constipation

•    itching and rash

•    headache, dizziness, drowsiness

•    sleeping problems, nervousness

•    increase or decrease in the number of white blood cells in your blood

•    blood test abnormalities due to liver or kidney problems

•    general weakness.

•    fungal infection (and growth of other resistant bacteria)

Rare side effects (affects 1 to 10 users in 10,000):

•    severe diarrhoea containing blood or mucus that may be due to inflammation of the bowels (see also “Take special care with Levofloxacin 5 mg/ml)

•    tingling sensation in the hands and feet, trembling,

•    fits

•    anxiety, depression, psychotic reactions, restlessness and confusion

•    fast, irregular or pounding heartbeats,

•    abnormally low blood pressure

•    tendon pain and inflammation (see also “Take special care with Levofloxacin 5 mg/ml”)

•    joint pain or muscle pain

•    decrease in the number of blood platelets leading to a tendency to bruise and bleed easily.

•    decrease in the number of neutrophils (a type of white blood cell) in your blood

•    shortness of breath, wheezing

•    hives (urticaria)

Very rare side effects (affects less than 1 user in

10,000)

•    severe decrease in the number of white blood cells (agranulocytosis) leading to symptoms such a s recurrence or persistence of fever, sore throat and feeling ill

•    feeling faint due to a fall in blood sugar to a very low level (hypoglycaemia). This is especially important if you are diabetic.

•    hallucinations, psychotic reactions with risk of suicidal thoughts or acts. (See also “Take special care with Levofloxacin 5m/ml).

•    weakness, tingling or numbness of arms and legs, or face (See also “Take special care with Levofloxacin 5m/ml).

•    impaired sense of taste and smell

•    visual disturbances (blurred or double vision)

•    hearing problems

•    allergic inflammation of the lungs which causes breathlessness, cough and raised temperature

•    inflammation of the liver (hepatitis)

•    tendon rupture (see also “Take special care with Levofloxacin 5 mg/ml”).

•    muscle weakness, which may be of special importance in patients with myasthenia gravis (a rare disorder of the nervous system).

•    acute kidney failure which may be due to allergic kidney reactions (interstitial nephritis).

•    abnormally high temperature

Not known (frequency cannot be estimated from available data)

•    increased sweating

•    decrease in the number of all types of blood cells (pantocytopenia)

•    reduction in red blood cells which makes the skin pale or yellow and cause weakness or breathlessness (haemolyic anaemia)

•    ringing or whistling sound in the ears

•    abnormal fast heart rhythm, life threatening irregular heart rhythm, alteration of the heart rhythm (called “prolongation of QT interval”, seen on ECG, electrical recording of the heart)

•    severe liver problems, symptoms being a loss of appetite, yellowing of your skin or white of your eyes (jaundice), dark coloured urine, itching or abdominal pain or tenderness. (see also “Take special care with Levofloxacin 5 mg/ml)

•    severe muscle aches and pains, tenderness weakness or cramps (rhabdomyolysis)

•    Pain in your fingers toes, chest or back.

•    Hypersensitivity (allergic reaction)

Other reactions that have been associated to fluorquinolones and therefore may occur with Levofloxacin 5 mg/ml:

•    Disorders of movement including walking difficulties (extrapyramidal symptoms)

•    Allergic inflammation of small blood vessels (Hypersenstivity vasculitis)

•    Attacks of porphyria in patients with porphyria (a very rare metabolic disease)

Any bacterial treatment that kills certain germs may lead to a disturbance of the microorganisms (bacteria/fungi) that are normally found in humans. Consequently the number of other bacteria or fungi may increase, which in some cases requires treatment.

If any of these side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

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5. How to store Levofloxacin 5 mg/ml

•    As with all medicines it must be kept out of the reach and sight of children.

•    It should be kept in its outer carton in order to protect from light until use.

•    Your doctor or nurse will ensure that your medicine is properly stored.

•    There is an expiry date on the carton after EXP, your doctor or nurse will check that this date has n o t passed. The expiry date refers to the last day of the month.

6. Further information

What Levofloxacin 5 mg/ml contains

•    the active substance (the ingredient that makes this medicine work) 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.

•    Each 50 ml of solution for infusion contains 250 mg of levofloxacin.

the other ingredients are:

-    sodium chloride,

-    hydrochloric acid (for pH adjustment)

-    sodium hydroxide (for pH adjustment)

-    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 particles.

It is supplied in a 100 ml plastic bag containing 100 ml or 50 ml of solution for infusion. Packs of 1,5 and 20 bags are available.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare Limited Sage House 319, Pinner Road North Harrow Middlesex HA1 4HF United Kingdom

Manufacturer

Polpharma, S.A., 83-200 Starogard Gdanski, Poland This leaflet was last revised in 10/2012.

< 10 ml/min (including    then:    then:    then:

hemodialysis and CAPD)¹    125 mg/48 h    125 mg/24 h    125 mg/24 h

1

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

Do not use the product after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month.

Keep the bag in its outer carton in order to protect from light. The shelf life of the product after removal of the bag from the outer carton is 24 hours when stored under indoor light conditions.

Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C upon further dilution of the product with compatible solutions.

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

For single use only. Discard any unused solution.

Any unused product or waste material should be disposed of in accordance with local requirements. These measures will help to protect the environment.

Compatibilities:

This medicine may be given alone or with one of the following solutions:

sodium chloride 9 mg/ml (0.95%),

glucose 50 mg/ml (5%),

glucose 25 mg/ml (2.5%) in Ringer's solution,

Incompatibilities:

This medicine should not be mixed with heparin or alkaline solutions (e.g. sodium hydrogen carbonate).

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