PACKAGE LEAFLET: INFORMATION FOR THE USER

Levoxigram 250 mg film-coated tablets, 500 mg film-coated tablets

Levofloxacin
Equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Levoxigram is and what it is used for
What you need to know before taking Levoxigram
How to take Levoxigram
Possible side effects
How to store Levoxigram
Contents of the pack and other information

1. WHAT LEVOXIGRAM IS AND WHAT IT IS USED FOR

Levoxigram tablets contain the active substance levofloxacin. This medicine belongs to a
group of medicines called antibiotics. Levofloxacin is a "quinolone" antibiotic. This
medicine works by killing the bacteria responsible for infections in the body.
Levoxigram tablets can be used to treat the following infections:

Of the paranasal sinuses
Of the lungs, in patients with chronic respiratory disorders or pneumonia
Of the urinary tract, including kidneys and bladder
Of the prostate, where a persistent infection may develop
Of the skin and subcutaneous tissue, including muscles. These are sometimes referred to as "soft tissues".

2. WHAT YOU SHOULD KNOW BEFORE TAKING LEVOXIGRAM

Do not take Levoxigram:

if you are allergic to levofloxacin, to any other quinolone antibiotic such as moxifloxacin, ciprofloxacin or ofloxacin, or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
if you have ever had epilepsy.
if you have ever had tendon problems, such as tendinitis, related to treatment with a "quinolone antibiotic". Tendons are fibrous structures that connect muscles to the skeleton.
if you are a child or adolescent during the growth period.
if you are pregnant, plan to become pregnant, or think you may be pregnant.
if you are breastfeeding. Do not take this medicine if any of the above apply to you. If you have any doubts, consult your doctor or pharmacist before taking Levoxigram.

Warnings and precautions
Before taking this medicine
You must not take quinolone/fluoroquinolone antibacterial medicines, including Levoxigram, if in the past you have experienced any serious adverse reaction during treatment with a quinolone or fluoroquinolone. In such cases, inform your doctor as soon as possible.
While taking this medicine
Rarely, joint pain and swelling, tendon inflammation or tendon rupture may occur.
The risk is higher if you are elderly (over 60 years of age), have received an organ transplant, have kidney problems, or are being treated with corticosteroids. Tendon inflammation and rupture may occur within the first 48 hours of treatment and up to several months after stopping Levoxigram. At the first signs of tendon pain or inflammation (for example, in the ankle, wrist, elbow, shoulder or knee), stop treatment with Levoxigram, contact your doctor and rest the affected area. Avoid unnecessary movements, as the risk of tendon rupture may increase.
Rarely, symptoms of nerve damage (neuropathy) such as pain, burning, tingling, numbness and/or weakness, particularly in the feet and legs or hands and arms, may occur. In such cases, stop treatment with Levoxigram and contact your doctor immediately to prevent permanent nerve damage.

If you experience sudden involuntary jerks, fasciculations or muscle contractions – contact a doctor immediately, as these may be signs of myoclonus. Your doctor may need to stop levofloxacin treatment and start appropriate therapy.
If you experience fatigue, pale skin, bruising, uncontrolled bleeding, fever, sore throat and a severe worsening of your general condition, or if you feel your resistance to infections has decreased – contact a doctor immediately, as these may be signs of a blood disorder. Your doctor should monitor your blood counts via a complete blood count (CBC). If blood tests are abnormal, your doctor may need to stop treatment.

Serious, prolonged, disabling and potentially irreversible side effects
Fluoroquinolone/quinolone antibacterial medicines, including Levoxigram, have been associated with very rare but serious side effects, some of which may be prolonged (lasting months or years), disabling or irreversible. These include tendon, muscle and joint pain in arms and legs, difficulty walking, abnormal sensations such as pricking, tingling, itching, numbness or burning (paresthesia), sensory organ disturbances such as changes in vision, taste, smell and hearing, depression, memory impairment, severe fatigue and severe sleep disturbances.
If you experience any of these side effects after taking Levoxigram, contact your doctor immediately before continuing treatment. Your doctor will decide together with you whether to continue treatment and may consider using an antibiotic from another class.
Contact your doctor or pharmacist before taking Levoxigram:

if you have developed a severe skin reaction, skin peeling, blisters and/or mouth ulcers after taking any medicine containing levofloxacin.
if you are 60 years of age or older.
if you are taking corticosteroids, sometimes called steroids (see “Other medicines and Levoxigram”).
if you have had seizures (convulsions).
if you have suffered brain damage due to stroke or other brain injury.
if you have kidney problems.
if you have a known condition called “glucose-6-phosphate dehydrogenase deficiency”. Administration of this medicine increases the likelihood of developing serious blood problems.
if you have suffered from mental health problems.
if you have been diagnosed with an enlargement or “bulging” of a large blood vessel (aortic aneurysm or peripheral aneurysm of a large blood vessel).
if you have previously experienced episodes of aortic dissection (a tear in the wall of the aorta).
if you have been diagnosed with insufficiency of one of the heart valves (aortic or mitral regurgitation).
if you have a family history of aortic aneurysm, aortic dissection or congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, Turner syndrome, Sjögren's syndrome [an autoimmune inflammatory disease], or if you have vascular diseases such as Takayasu arteritis, giant cell arteritis, Behcet's syndrome, high blood pressure, known atherosclerosis, rheumatoid arthritis [an autoimmune inflammatory disease] or endocarditis [heart inflammation]).
if you have heart problems: you should use caution when taking this type of medicine if you were born with or have a family history of QT interval prolongation (seen on electrocardiogram, the electrical tracing of the heart), have an electrolyte imbalance in the blood (especially low potassium or magnesium levels), have a very slow heart rate (called “bradycardia”), have a weak heart (heart failure), have had a heart attack (myocardial infarction), are female or elderly, or are taking other medicines that may alter the electrocardiogram (see section “Other medicines and Levoxigram”).
if you have diabetes.
if you have had liver problems.
if you have myasthenia gravis.
if you have or suspect you have a S. aureus infection resistant to methicillin (MRSA).

If you have any doubts about whether any of the above may apply to you, consult your doctor or pharmacist before taking Levoxigram.
While taking Levoxigram:

if you experience sudden abdominal, chest or back pain, which may be a symptom of aortic aneurysm or dissection, go immediately to the emergency room. The risk may be higher if you are taking systemic corticosteroid medicines.
contact your doctor immediately if you notice a rapid onset of shortness of breath, especially when lying down, or swelling of the ankles, feet or abdomen, or new episodes of palpitations (sensation of rapid or irregular heartbeat).

Severe skin reactions
Severe skin reactions have been reported with the use of levofloxacin, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS).

SJS and TEN may initially appear on the body as reddish spots or circular patches, often with central blisters. Mouth, throat, nose, genital and eye ulcers (red, swollen eyes) may also occur. These severe skin rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread skin peeling and life-threatening or fatal complications.
DRESS initially presents with flu-like symptoms and a skin rash on the face, followed by widespread skin rash with fever, elevated liver enzyme levels in blood tests, increased levels of a type of white blood cell (eosinophilia) and swollen lymph nodes.

If you develop a severe skin rash or any of these other skin symptoms, stop taking levofloxacin and contact your doctor or seek immediate medical help.
Other medicines and Levoxigram
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because Levoxigram may affect how other medicines work. Some medicines may also affect how Levoxigram works.
In particular, inform your doctor if you are taking any of the following medicines. This is because
taking Levoxigram together with other medicines may increase the risk of side effects:

corticosteroids, sometimes called steroids – used to treat inflammation. The risk of developing tendon inflammation and/or tendon rupture is increased.
warfarin – used to thin the blood. The risk of bleeding is increased. Your doctor may ask you to have regular blood tests to monitor blood clotting.
theophylline – used for breathing problems. The risk of seizures (epileptic fits) is increased if you take theophylline together with Levoxigram.
non-steroidal anti-inflammatory drugs (NSAIDs) – used for pain and inflammation, such as aspirin, ibuprofen, fenbufen, ketoprofen and indomethacin. The risk of seizures (epileptic fits) is increased when taken together with Levoxigram.
cyclosporine – used for organ transplants. The risk of experiencing typical cyclosporine side effects is increased.
medicines known to affect heart rhythm. These include medicines used to treat abnormal heart rhythm (antiarrhythmics such as quinidine, hydroquinidine, disopyramide, sotalol, dofetilide, ibutilide and amiodarone), depression (tricyclic antidepressants such as amitriptyline and imipramine), psychiatric disorders (antipsychotics), and bacterial infections (macrolide antibiotics such as erythromycin, azithromycin and clarithromycin).
probenecid – used for gout, and cimetidine – used for ulcers and heartburn.

Use particular caution when taking any of these medicines with Levoxigram.
Your doctor may prescribe a lower dose if you have kidney problems.
Do not take Levoxigram tablets together with the following medicines. This is because the
effectiveness of Levoxigram tablets may be affected:

iron salts in tablets (for anemia), zinc supplements, antacids containing magnesium or aluminium (for acidity or heartburn), didanosine or sucralfate (for gastric ulcers). See section 3 “if you are taking iron salts in tablets, zinc supplements, antacids, didanosine or sucralfate”.

Urine testing for opiates
In patients taking Levoxigram, urine tests may give “false-positive” results for strong painkillers called “opiates”. If your doctor considers it necessary to perform a urine test, inform them that you are taking Levoxigram.
Tuberculosis testing
This medicine may cause “false-negative” results in certain laboratory tests used to detect bacteria causing tuberculosis.
Pregnancy and breastfeeding
Do not take this medicine if:

you are pregnant, may become pregnant or think you may be pregnant.
you are breastfeeding or think you may breastfeed.

Driving and operating machinery
Some side effects may occur after taking this medicine, including dizziness, drowsiness, subjective sensation of movement (vertigo) or visual disturbances. Some of these side effects may impair your concentration and reaction speed. If this occurs, do not drive or operate machinery requiring high attention levels.
Levoxigram tablets contain sunset yellow (E110)
This medicine contains the colour sunset yellow (E110), which may cause allergic reactions.

3. HOW TO TAKE LEVOXIGRAM

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you are unsure, ask your doctor or pharmacist.

Taking this medicine

Take this medicine by mouth
Swallow the tablets whole with a glass of water
The tablets may be taken during meals or at any time between meals
The tablets may be divided into two equal parts

Protect your skin from sunlight
Do not expose yourself to direct sunlight during treatment with this medicine and for 2 days after
treatment has ended. This is because your skin will become much more sensitive to sunlight and may burn,
itch, or develop severe blistering if you do not follow the precautions listed below:

Make sure to use sunscreen creams with a high sun protection factor
Always wear a hat and clothing covering arms and legs
Avoid sunbeds (tanning beds)

If you are already taking iron tablets, zinc supplements, antacids, didanosine, or
sucralfate

Do not take these medicines at the same time as Levoxigram tablets. Take the prescribed dose of these medicines at least 2 hours before or after taking Levoxigram tablets.

How much medicine to take

Your doctor will decide how much Levoxigram tablets you should take
The dose will depend on the type of infection you have and where in the body the infection is located
The duration of treatment depends on the severity of the infection
If you think that the effect of the medicine is too weak or too strong, do not change the dose on your own initiative; instead, consult your doctor.

Use in adults and elderly patients:
Sinus infection

Two Levoxigram 250 mg tablets once daily
Or one Levoxigram 500 mg tablet once daily

Respiratory tract infections in patients with chronic respiratory problems

Two Levoxigram 250 mg tablets once daily
Or one Levoxigram 500 mg tablet once daily

Pneumonia

Two Levoxigram 250 mg tablets once or twice daily
Or one Levoxigram 500 mg tablet once or twice daily

Urinary tract infections, including kidneys or bladder

One or two Levoxigram 250 mg tablets once daily
Or ½ or one Levoxigram 500 mg tablet once daily

Prostate infections

Two Levoxigram 250 mg tablets once daily
Or one Levoxigram 500 mg tablet once daily

Skin and soft tissue infections, including muscles

Two Levoxigram 250 mg tablets once or twice daily
Or one Levoxigram 500 mg tablet once or twice daily

Use in adults and elderly patients with kidney problems:
Your doctor may decide to prescribe you a reduced dose.
Use in children and adolescents:
This medicine must not be given to children or adolescents.
If you take more Levoxigram tablets than you should
If you accidentally take more tablets than prescribed, inform your doctor immediately or seek medical
advice straight away. Take the medicine pack with you. This will allow the doctor to know what you have
taken. The following side effects may occur: seizures (epileptic fits), confusion, dizziness, feeling faint,
tremor, and heart problems – which may lead to irregular heartbeat and feelings of discomfort (nausea) or
stomach burning.
If you forget to take a Levoxigram tablet
If you forget to take a dose, take it as soon as you remember, unless it is almost time for your next dose. Do
not take a double dose to make up for the missed dose.
If you stop taking Levoxigram tablets
Do not stop taking Levoxigram just because you feel better. It is important that you complete the full course
of tablets prescribed by your doctor. If you stop taking the tablets too early, the infection may return, your
condition may worsen, or the bacteria may develop resistance to the medicine.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them. Usually, these effects are mild or moderate in severity and often disappear after a short time.

Stop taking Levoxigram and go immediately to a doctor or hospital if you notice any of the following adverse reactions:

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

widespread rash, fever, elevated liver enzymes, blood abnormalities (eosinophilia), swollen lymph nodes and involvement of other body organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome). See also section 2.
syndrome associated with inadequate water excretion and low sodium levels (SIADH)
you have an allergic reaction. Signs may include: skin rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue
seeing or hearing things that are not real (hallucinations, paranoia), changes in thinking and uncertainty (psychotic reactions), with possible development of suicidal ideation or suicidal acts

Stop taking Levoxigram and go immediately to a doctor if you notice any of the following adverse reactions – you may require urgent medical treatment:

Rare

pain and inflammation of tendons or ligaments which in some cases may rupture. The Achilles tendon is most commonly affected.
seizures

Not known (frequency cannot be estimated from the available data)

watery diarrhoea, possibly with blood, accompanied by abdominal cramps and high fever. This may indicate a serious intestinal disorder
burning, tingling, pain or numbness. These signs may indicate a condition called "neuropathy"
severe skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear on the body as reddish spots or circular patches, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. See also section 2.
loss of appetite, yellowing of the skin and eyes, dark-coloured urine, itching or abdominal pain. These may be signs of liver problems, which may include fatal liver failure (liver failure that can lead to death).

If your vision becomes blurred or you experience any eye discomfort while taking Levoxigram, consult an ophthalmologist immediately.

Inform your doctor if any of the following adverse reactions worsen or last for more than a few days:

Common (may affect up to 1 in 10 people)

difficulty sleeping
headache, dizziness
feeling unwell (nausea, vomiting) and diarrhoea
increased liver enzyme levels in the blood

Uncommon (may affect up to 1 in 100 people)

changes in the number of other bacteria or fungi, fungal infection called Candida, which may require treatment
changes in white blood cell count shown in blood test results (leucopenia, eosinophilia)
feeling stressed (anxiety), confusion, nervousness, drowsiness, tremor, vertigo
shortness of breath (dyspnoea)
altered taste, loss of appetite, stomach discomfort or indigestion (dyspepsia), stomach pain, bloating (flatulence), constipation
itching and skin rash, severe itching or hives, excessive sweating (hyperhidrosis)
joint pain or muscle pain
blood tests may show abnormal results due to liver problems (increased bilirubin) or kidney problems (increased creatinine)
generalised weakness

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

bruising and increased tendency to bleed due to reduced platelet count in the blood (thrombocytopenia)
low white blood cell count (neutropenia)
decreased blood sugar levels (hypoglycaemia). This is important for people with diabetes
feeling depressed, mental disturbances, restlessness (agitation), unusual dreams or nightmares
tingling sensation in hands and feet (paraesthesia)
hearing problems (tinnitus) or vision problems (blurred vision)
unusually fast heartbeat (tachycardia) or low blood pressure (hypotension)
muscle weakness. This is important for patients with myasthenia gravis (a rare nervous system disorder)
changes in kidney function and occasional kidney failure, which may be caused by an allergic reaction affecting the kidneys called interstitial nephritis
fever
clearly defined erythematous patches, with or without blister formation, developing within hours of levofloxacin administration and healing with residual redness; these usually recur at the same skin or mucosal site upon subsequent exposure to levofloxacin

Not known:

decrease in red blood cells (anaemia). This may lead to paleness or yellowish skin due to damage to red blood cells and a decrease in all types of blood cells (pancytopenia)
bone marrow stops producing new blood cells, which may cause fatigue, reduced ability to fight infections and uncontrolled bleeding (bone marrow failure)
fever, sore throat and a general feeling of illness that does not go away. This may be due to a reduced number of white blood cells in the blood (agranulocytosis)
lack of blood flow (anaphylactic shock)
increased blood sugar levels (hyperglycaemia) or decreased blood sugar levels leading to coma (hypoglycaemic coma). This is important for people with diabetes
changes in smell, loss of smell or taste (parosmia, anosmia, ageusia)
feeling extremely excited, euphoric, agitated or enthusiastic (mania)
difficulty moving or walking (dyskinesia, extrapyramidal disorders)
temporary loss of consciousness or posture (syncope)
temporary loss of vision
worsening or loss of hearing
unusually fast heartbeat, irregular heartbeat with life-threatening risk including cardiac arrest, changes in heartbeat rhythm (known as "prolongation of the QT interval" seen on electrocardiogram, electrical activity of the heart)
breathing difficulties or wheezing (bronchospasm)
allergic reactions affecting the lungs
inflammation of the pancreas (pancreatitis)
inflammation of the liver (hepatitis)
increased sensitivity of the skin to sunlight or ultraviolet rays (photosensitivity), darker skin areas (hyperpigmentation)
inflammation of blood vessels supplying the entire body due to an allergic reaction (vasculitis)
inflammation of the internal tissues of the mouth (stomatitis)
muscle breakdown and destruction (rhabdomyolysis)
redness and swelling of the joints (arthritis)
pain, including back, chest and extremity pain
sudden involuntary jerks, fasciculations or muscle contractions (myoclonus)
attacks of porphyria in patients who already suffer from porphyria (a very rare metabolic disorder)
persistent headache with or without blurred vision (benign intracranial hypertension)

Very rare cases of prolonged (lasting months or years) or permanent adverse drug reactions, such as tendon inflammation, tendon rupture, joint pain, pain in arms or legs, difficulty walking, abnormal sensations such as pricking, tingling, tickling, burning, numbness or pain (neuropathy), depression, fatigue, sleep disturbances, memory impairment and changes in hearing, vision, taste and smell, have been associated with the use of quinolone and fluoroquinolone antibiotics, in some cases regardless of pre-existing risk factors.

Cases of aortic wall dilation and weakening or aortic wall tear (aneurysms and dissections), with possible rupture that may be fatal, as well as cases of blood regurgitation from heart valves, have been reported in patients treated with fluoroquinolones. See also section 2.

Reporting of adverse reactions

If you experience any adverse reaction, including those not listed in this leaflet, tell your doctor or pharmacist. You can also report adverse reactions directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE LEVOXIGRAM

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and blister after "SCAD." or "EXP". The expiry date refers to the last day of that month.
Keep the blister in the carton to protect it from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACK CONTENTS AND OTHER INFORMATION

What Levoxigram contains
The active substance is levofloxacin.
Each Levoxigram 250 mg film-coated tablet contains levofloxacin hemihydrate equivalent to 250 mg of levofloxacin.
Each Levoxigram 500 mg film-coated tablet contains levofloxacin hemihydrate equivalent to 500 mg of levofloxacin.

The other components are:
Tablet core: Microcrystalline cellulose, hydroxypropylcellulose, crospovidone, magnesium stearate.
Film coating: Hypromellose, FD&C Blue No. 2 indigo carmine – aluminium lake (E132), FD&C Yellow No. 6 sunset yellow – aluminium lake (E110), iron oxide red (E172), macrogol 4000, titanium dioxide (E171). Additionally, the 500 mg tablets contain yellow iron oxide (E172).

Description of the appearance of Levoxigram tablets and packaging contents
Levoxigram 250 mg tablets are pink, oblong, biconvex, with a break line.
Levoxigram 500 mg tablets are orange, oblong, biconvex, with a break line.

Levoxigram 250 mg film-coated tablets are packaged in blisters and available in pack sizes of 1, 5, 7 and 10 tablets.
Levoxigram 500 mg film-coated tablets are packaged in blisters and available in pack sizes of 1, 5, 7 and 10 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder:
Aesculapius Farmaceutici S.r.l.
Via Cefalonia, 70 - 25124 Brescia
Italy

Manufacturer:
Pharmathen S.A.
6 Dervenekion str.,
15351 Pallini, Attiki
Greece