Gray: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE USER

GRAY 500 mg film-coated tablets

Levofloxacin
Generic 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 other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What GRAY 500 mg is and what it is used for
What you need to know before taking GRAY 500 mg
How to take GRAY 500 mg
Possible side effects
How to store GRAY 500 mg
Contents of the pack and other information

1. What GRAY 500 mg is and what it is used for

GRAY 500 mg is a broad-spectrum antibiotic, which means that GRAY 500 mg works by eliminating many types of bacteria that can cause infections (pathogens). GRAY 500 mg contains the active substance levofloxacin. This active substance belongs to a class of antibiotics called quinolones.
In adults with mild to moderate infections, GRAY 500 mg is used to treat infections to which the medicine is active, such as:

sinus infections
lung and lower respiratory tract infections: acute exacerbations of chronic bronchitis or pneumonia
complicated urinary tract infections (e.g. involving the kidneys)
chronic bacterial prostatitis (prostatitis)
skin and soft tissue infections

2. What you need to know before taking GRAY 500 mg

DO NOT take GRAY 500 mg

if you are allergic (hypersensitive) to levofloxacin, to any excipient in GRAY 500 mg (see section 6), or to other quinolone antibiotics such as moxifloxacin, ciprofloxacin, or ofloxacin.
if you suffer from epilepsy
if you have a history of tendon problems related to treatment with quinolone antibiotics
during pregnancy
during breastfeeding.

These tablets must not be administered to children or adolescents who are still growing.
Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine:

if you have developed a severe skin reaction or skin peeling, blisters and/or mouth ulcers after taking any medicine containing levofloxacin.
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 aortic wall).
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 or aortic dissection, congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Sjögren's syndrome [an autoimmune inflammatory disease], or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet's disease, known high blood pressure or atherosclerosis, rheumatoid arthritis [an autoimmune inflammatory disease], or endocarditis [inflammation of the heart]).
you must not take quinolone/fluoroquinolone antibacterial medicines, including GRAY 500 mg, if you have previously had any serious adverse reaction during treatment with a quinolone or fluoroquinolone. In such cases, inform your doctor as soon as possible.
in severe cases of pneumonia caused by certain pathogens (e.g. S. pneumoniae). Consult your doctor, as GRAY 500 mg may not be the optimal therapy.
in hospital-acquired infections caused by certain pathogens (e.g. Pseudomonas aeruginosa). Consult your doctor, as these may require combination therapy.
in infections caused by certain pathogens (so-called MRSA). Consult your doctor, as these may require combination therapy.
if you develop severe, persistent and/or bloody diarrhoea during or after treatment with GRAY 500 mg. Inform your doctor immediately, as this diarrhoea may be a symptom of a serious intestinal inflammation (enterocolitis), which may occur following antibiotic treatment. Stop taking GRAY 500 mg. Your doctor will change your treatment. Do not take antidiarrhoeal medicines that slow intestinal movements. For this, consult your doctor or pharmacist.
if you are prone to seizures. During treatment with GRAY 500 mg, the risk of epileptic seizures may be higher if you have previously had brain damage such as a stroke or severe head injury. Inform your doctor if you have experienced such events in the past. Do not take the tablets if you suffer from epilepsy. The tendency to cramps may also be increased during concomitant treatment with fenbufen and other similar non-steroidal anti-inflammatory drugs used for pain and inflammation, such as aspirin, ibuprofen, ketoprofen, and indometacin, or with theophylline (see also “Use with other medicines”). If seizures occur, treatment must be discontinued.
if you suffer from glucose-6-phosphate dehydrogenase deficiency (an inherited metabolic disorder). Patients with this condition may be prone to destruction of red blood cells (haemolysis) when treated with quinolone antibacterial agents. Therefore, GRAY 500 mg should be used with caution in these patients.
if you suffer from renal impairment. Ask your doctor how the dose should be adjusted (see section 3 “How to take GRAY 500 mg”).
if severe allergic reactions (hypersensitivity) occur (sometimes after the initial dose). Seek immediate medical advice or go to the nearest hospital. Stop treatment with GRAY 500 mg.
if you are taking oral hypoglycaemic agents (e.g. glibenclamide) or insulin. It is necessary to monitor your blood sugar levels carefully, as your blood glucose levels may drop too low. Symptoms may include: excessive hunger, nervousness, sweating, trembling.
if you are exposed to strong sunlight or ultraviolet rays. Photosensitisation (hypersensitivity to light with sunburn-like reactions) is a rare event with levofloxacin. Nevertheless, it is recommended to avoid unnecessary exposure to strong sunlight or artificial ultraviolet rays (e.g. sunlamps, sunbeds) to prevent photosensitisation.
if you are receiving concomitant treatment with a vitamin K antagonist (certain agents affecting blood clotting time, e.g. warfarin, phenprocoumon). Blood clotting times and bleeding tendency may increase. Blood clotting tests should be monitored (see also section “Use with other medicines”).
if you suffer from psychosis or have previously suffered from psychiatric illness. Psychotic reactions have been reported in patients treated with quinolones, including levofloxacin. In very rare cases, these may progress to suicidal thoughts and self-harming behaviour—sometimes after a single dose of levofloxacin. If such reactions occur, discontinue treatment and inform your doctor. Your doctor will decide on appropriate measures and further treatment.

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 as flu-like symptoms and a skin rash on the face, followed by an extensive 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 skin symptoms, stop taking levofloxacin and contact your doctor or seek immediate medical help.
Before taking Gray 500 mg

Heart problems Special caution is required when using this type of medicine if you were born with or have a family history of prolonged QT interval (seen on ECG, an electrical recording of the heart), have an electrolyte imbalance in the blood (especially low levels of potassium or magnesium), have a very slow heart rate (bradycardia), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), if you are female or elderly, or if you are taking other medicines that may cause abnormal changes on ECG (see section "Use with other medicines").
if you have symptoms of nerve damage, such as sensory disturbances in the hands and feet. In such cases, consult your doctor immediately. Discontinue GRAY 500 mg to prevent possible damage.
if you are scheduled for a urine test for opiates. The test may give a false positive result. It may be necessary to confirm a positive result using more specific methods.
if you have symptoms of liver disease, such as jaundice, dark urine, itching, loss of appetite (anorexia), or a soft abdomen. Stop treatment with GRAY 500 mg and consult your doctor.
in cases of myasthenia gravis

During treatment with GRAY:

if you experience sudden, severe pain in the abdomen, chest, or back, 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.
Inform your doctor immediately if you notice a rapid onset of breathlessness, especially when lying down, or swelling of the ankles, feet, or abdomen, or new episodes of palpitations (sensation of rapid or irregular heartbeat).
If you begin to experience sudden involuntary jerks, fasciculations, or muscle contractions—seek medical advice immediately, as these may be signs of myoclonus. Your doctor may need to discontinue levofloxacin treatment and start appropriate therapy.
If you develop nausea, general malaise, severe discomfort or persistent pain or worsening pain in the stomach area, or vomiting, contact your doctor immediately, as these may be signs of inflammation of the pancreas (acute pancreatitis).
If you experience fatigue, pale skin, bruising, uncontrolled bleeding, fever, sore throat, and severe worsening of your general condition, or if you feel your resistance to infections has decreased—seek immediate medical advice, as these may be signs of blood disorders. Your doctor should monitor your blood with a complete blood count. If blood tests are abnormal, your doctor may need to discontinue treatment.

Rarely, joint pain and swelling, and inflammation or rupture of tendons may occur. The risk is higher if you are elderly (over 60 years), have received an organ transplant, have kidney problems, or are taking corticosteroids. Tendon inflammation and rupture may occur within the first 48 hours of treatment and up to several months after stopping treatment with GRAY 500 mg. At the first signs of tendon pain or inflammation (e.g. in the ankle, wrist, elbow, shoulder, or knee), discontinue treatment with GRAY 500 mg, consult 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, discontinue treatment with GRAY 500 mg and inform your doctor immediately to prevent permanent nerve damage.
If your vision deteriorates or your eyes are otherwise affected, consult an ophthalmologist immediately.
Serious, prolonged, disabling, and potentially irreversible side effects
Fluoroquinolone/quinolone antibacterial medicines, including GRAY 500 mg, have been associated with very rare but serious side effects, some of which are prolonged (lasting months or years), disabling, or may not improve. These include tendon, muscle, and joint pain in the arms and legs, difficulty walking, abnormal sensations such as pricking, tingling, itching, numbness, or burning (paraesthesia), sensory organ disturbances such as changes in vision, taste, smell, or hearing, depression, memory impairment, severe fatigue, and severe sleep disturbances.
If you experience any of these side effects after taking GRAY 500 mg, seek immediate medical advice before continuing treatment. Your doctor will decide with you whether to continue treatment and may consider using an antibiotic from another class.
Children
Children or adolescents who are still growing must not take GRAY 500 mg, as the risk of damage to joint tissues cannot be excluded.
Elderly
Renal impairment is common in this age group. Therefore, you should ask your doctor whether a dose adjustment may be necessary (see section 3 “How to take GRAY 500 mg”).
Other medicines and GRAY 500 mg
You must inform your doctor if you are taking other medicines that may alter heart rhythm: medicines belonging to the class of antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (macrolide class), and some antipsychotics.

Corticosteroids, sometimes called steroids—used for inflammation. You are more likely to experience tendon inflammation and/or rupture.
Vitamin K antagonists, e.g. warfarin, phenprocoumon—used to thin the blood. The risk of bleeding increases. Your doctor may need to perform regular blood tests to assess your blood's ability to clot.
Theophylline—used for respiratory problems: increases the likelihood of seizures when taken with GRAY 500 mg.
Non-steroidal anti-inflammatory drugs (NSAIDs)—used for pain and inflammation such as aspirin, ibuprofen, fenbufen, ketoprofen, and indometacin: increases the likelihood of seizures when taken with GRAY 500 mg.
Cyclosporine—used after organ transplantation: the effect of cyclosporine may be prolonged when used in combination with GRAY 500 mg.
Probenecid—used for gout and cimetidine—used for ulcers and heartburn: the elimination (renal clearance) of levofloxacin is slightly reduced. However, this is unlikely to affect your treatment. Nevertheless, be cautious when taking GRAY 500 mg together with drugs such as probenecid and cimetidine, which affect renal elimination. If you have kidney problems, your doctor may prescribe a reduced dose.

Do not take GRAY 500 mg at the same time as the following medicines. This is because interactions with the mechanism of action of GRAY 500 mg may occur:

Iron tablets (for anaemia), zinc supplements, antacids containing magnesium or aluminium (for acidity or heartburn), didanosine, or sucralfate (for stomach ulcers). Therefore, take GRAY 500 mg at least 2 hours before or after taking these medicines.

Urine tests for opiates
Urine tests may show 'false positive' results for strong painkillers called 'opiates' in people taking GRAY 500 mg. If your doctor is about to prescribe urine tests, tell them you are taking GRAY 500 mg.
Tuberculosis testing
This medicine may cause "false negative" results in certain laboratory tests that detect the bacteria causing tuberculosis.
GRAY 500 mg with food, drinks and alcohol
Do not drink alcohol during treatment with GRAY 500 mg.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
You must not take GRAY 500 mg if you are pregnant, trying to become pregnant, breastfeeding, or planning to breastfeed. Inform your doctor if you find out you are pregnant while taking GRAY 500 mg.
Driving and using machines
Some side effects of GRAY 500 mg such as dizziness, drowsiness, and visual disturbances (see also section “4. Possible side effects”) may impair your ability to concentrate and react and may therefore pose a risk in situations where these abilities are particularly important. Do not drive, operate machinery, or perform activities without secure support if you notice that these abilities are impaired. Exercise particular caution when consuming alcohol.
Gray contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take GRAY 500 mg

Take this medicine exactly as directed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
Recommended dose: see Table 1

Table 1: Dosage in patients with normal renal function
Sinusitis (sinus infection):	1 film-coated GRAY 500 mg tablet once daily (equivalent to 500 mg of levofloxacin).
Acute exacerbation of chronic bronchitis (lung infection in people with long-term respiratory problems):	from half a film-coated GRAY 500 mg tablet (equivalent to 250 mg of levofloxacin) to one film-coated GRAY 500 mg tablet (equivalent to 500 mg of levofloxacin) once daily.
Pneumonia:	1 film-coated GRAY 500 mg tablet once or twice daily (equivalent to 500 or 1000 mg of levofloxacin).
Urinary tract infections:	Half a film-coated GRAY 500 mg tablet once daily (equivalent to 250 mg of levofloxacin).
Chronic bacterial prostatitis:	1 film-coated GRAY 500 mg tablet once daily (equivalent to 500 mg of levofloxacin).
Skin and soft tissue infections:	Half a film-coated GRAY 500 mg tablet once daily (equivalent to 250 mg of levofloxacin) or 1 film-coated GRAY 500 mg tablet once or twice daily (equivalent to 500 or 1000 mg of levofloxacin).

Since levofloxacin is primarily excreted by the kidneys, the dose must be adjusted in patients with impaired renal function. For details, refer to the table below:
Table 2: Dosing in patients with reduced renal function
Dosage regimen
250 mg/24 hours 500 mg/24 hours 500 mg/12 hours
Creatinine clearance First dose: 250 mg First dose: 500 mg First dose: 500 mg
50 – 20 ml/min then: 125 mg/24 hours then: 250 mg/24 hours then: 250 mg/12 hours
19 – 10 ml/min then: 125 mg/48 hours then: 125 mg/24 hours then: 125 mg/12 hours
<10 ml/min (including hemodialysis and
then: 125 mg/48 hours then: 125 mg/24 hours then: 125 mg/24 hours
CAPD)
= No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Dosage adjustment is not necessary if you have impaired liver function. Levofloxacin is only minimally metabolized in the liver.
How to take this medicine
Swallow the film-coated tablets whole without chewing, with an adequate amount of liquid (e.g., ½ to 1 glass of water). If you need to adjust the dose, you may break the film-coated tablets along the break line. You may take the film-coated tablets with meals or at any time between meals.
See also section “Other medicines and GRAY 500 mg”.
Duration of treatment
The duration of treatment will depend on the severity of your infection. Your doctor will determine the optimal duration of treatment.
If you notice that the effect of GRAY 500 mg is too strong or too weak, inform your doctor or pharmacist.
If you take more GRAY 500 mg than you should
If you accidentally take one extra film-coated tablet of GRAY 500 mg, probably nothing will happen. However, if you accidentally take several extra film-coated tablets, contact your doctor immediately. You may experience the following symptoms:

central nervous system symptoms (confusion, dizziness, reduced level of consciousness, and epileptic seizures)
gastrointestinal reactions such as nausea and mucosal erosions
certain changes in cardiac function (prolongation of the QT interval). Therefore, your cardiac function should be monitored by your doctor (ECG) in case of overdose. The doctor will initiate treatment according to your symptoms (e.g., gastric lavage or administration of antacids). Levofloxacin is not removed from the body by dialysis. There is no specific antidote.

If you forget to take GRAY 500 mg
Take the missed dose as soon as you remember, unless it is almost time for your next dose. In that case, continue taking GRAY 500 mg at your usual time and at the dose prescribed by your doctor. Do not take a double dose to make up for the forgotten tablet.
If you stop taking GRAY 500 mg
Do not stop taking GRAY 500 mg without approval from your doctor. Treatment may fail if you stop too early.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Usually, these effects are mild or moderate in severity and often disappear after a short time.
The assessment of the frequency of side effects is based on the following classification:
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Frequency not known: frequency cannot be estimated from the available data

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

Stop taking GRAY and go immediately to the doctor or hospital if you experience the following side effect:
Very rare

you have an allergic reaction. Signs may include: skin rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue

Stop taking GRAY and go immediately to the doctor if you experience any of the following side effects – you may need urgent medical treatment:
Rare

watery diarrhoea, possibly with blood, sometimes accompanied by stomach cramps and high fever. This could be a sign of a serious intestinal problem
pain and inflammation of tendons or ligaments, which in some cases may rupture. The Achilles tendon is most frequently affected
seizures
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)

Very rare

burning, tingling, pain or numbness. These signs may indicate a condition called "neuropathy"

Frequency not known

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 can include fatal liver failure (liver failure that can cause death)
nausea, general feeling of discomfort, stomach upset or pain, or vomiting. These could be signs of inflammation of the pancreas (acute pancreatitis). See section 2.

If your vision becomes blurred or if you experience any eye discomfort while taking GRAY, consult an ophthalmologist immediately.
Inform your doctor if any of the following side effects worsen or last longer than a few days:
Common

difficulty sleeping
headache, dizziness
frequent loose bowel movements (diarrhoea), feeling unwell (nausea, vomiting)
increased blood levels of certain liver enzymes

Uncommon

changes in the number of other bacteria or fungi, fungal infection called Candida, which may require treatment
reduction in the number of white blood cells (leucopenia), increase in certain blood cells (eosinophilia)
feeling of stress (anxiety), confusion, nervousness, drowsiness, tremor, dizziness
shortness of breath (dyspnoea)
altered taste, loss of appetite, stomach upset or indigestion (dyspepsia), stomach pain, bloating (flatulence), constipation
signs of reduced kidney function (elevated blood creatinine levels)
itching and skin rash, severe itching or hives, excessive sweating (hyperhidrosis)
joint pain or muscle pain
generalised weakness
signs of reduced liver function (elevated blood bilirubin levels)

Rare

rapid heartbeat (tachycardia)
decrease in blood platelets (thrombocytopenia), leading to increased bruising and bleeding
decrease in certain white blood cells (neutropenia)
exaggerated immune response (hypersensitivity)
low blood sugar levels (hypoglycaemia). This is important for people with diabetes
seeing or hearing things that are not there (hallucinations, paranoia), changes in thinking and mood (psychotic reactions), with possible development of suicidal thoughts or suicide attempts
feeling depressed, mental disturbances, feeling restless (agitation), unusual dreams or nightmares
tingling sensation in hands and feet (paraesthesia)
hearing problems (tinnitus) or vision problems (blurred vision)
drop in blood pressure
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 in the kidneys called interstitial nephritis
fever
clearly defined erythematous spots, with or without blistering, developing within a few hours of levofloxacin administration and healing with redness; these usually reappear at the same skin or mucosal site after subsequent exposure to levofloxacin

Frequency not known:

Heart problems: abnormally fast heartbeat, dangerously irregular heartbeat, changes in heart rhythm (called QT interval prolongation, seen on ECG, the heart's electrical activity)
decrease in all types of blood cells (pancytopenia); reduction in red blood cells due to damage to blood cells (haemolytic anaemia)
the bone marrow stops producing new blood cells, which may cause fatigue, reduced ability to fight infections, and uncontrolled bleeding (bone marrow failure)
severe decrease in certain white blood cells (agranulocytosis). This leads to severe symptoms (persistent or recurrent fever, sore throat, worsening general health)
anaphylactic shock (severe hypersensitivity reaction, see section “Take special care with GRAY 500 mg”). Anaphylactic and hypersensitivity reactions may sometimes occur even after the first dose
increased blood sugar levels (hyperglycaemia) or decreased blood sugar levels leading to coma (hypoglycaemic coma). This is important for people with diabetes
changes in the smell of things, loss of smell or taste (parosmia, anosmia, ageusia)
feeling very excited, euphoric, agitated or enthusiastic (mania)
difficulty moving or walking (dyskinesia, extrapyramidal disorders)
temporary loss of consciousness or posture (syncope)
temporary loss of vision, eye inflammation
worsening or loss of hearing
breathing difficulties or wheezing (bronchospasm)
allergic reactions affecting the lungs
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 blood throughout the body due to an allergic reaction (vasculitis)
inflammation of the internal tissues of the mouth (stomatitis)
muscle damage (rhabdomyolysis)
redness and swelling of joints (arthritis)
pain (including back, chest and extremity pain)
sudden involuntary jerks, fasciculations or muscle contractions (myoclonus)
porphyria attacks 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, arm or leg pain, difficulty walking, abnormal sensations such as pricking, tingling, tickling, burning, numbness or pain (neuropathy), fatigue, memory and concentration problems, mental health effects (which may include sleep disturbances, anxiety, panic attacks, depression and suicidal thoughts), as well as hearing, vision, taste and smell disturbances, have been associated with the use of quinolone and fluoroquinolone antibiotics, in some cases regardless of pre-existing risk factors.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

Seek immediate medical advice if a side effect appears suddenly or worsens rapidly, as certain adverse drug reactions (e.g. pseudomembranous colitis, certain blood abnormalities, severe anaphylactic or anaphylactoid reactions, severe liver disorders and severe skin reactions) can be life-threatening. In such cases, do not continue taking the medicine without medical advice.

5. How to store GRAY 500 mg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after Exp..
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions, but it is advisable to
keep GRAY 500 mg in the original blister and packaging and in a dry place.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how
to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What GRAY 500 mg contains
The active substance is levofloxacin. Each GRAY 500 mg tablet contains 500 mg of
levofloxacin.
The other components are:

For the tablet core: crospovidone, hypromellose, microcrystalline cellulose and sodium stearyl fumarate
For the coating: hypromellose, titanium dioxide (E171), talc, macrogol, yellow iron oxide (E172) and red iron oxide (E172).

Description of the appearance of GRAY 500 mg and package contents
Film-coated tablets for oral use. The tablets are oblong and have a pale yellow-white to reddish-white score line.
For GRAY 500 mg, tablets are available in packs containing 5 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Aurora Biofarma S.r.l., Via Nicola Antonio Porpora 127, 20131 Milano, Italy
Manufacturer
GENETIC S.P.A. – Contrada Canfora – 84084 Fisciano (SA), Italy

This patient information leaflet does not contain all the available information on this medicinal product. If you wish to obtain further information or have any questions, please consult your doctor or pharmacist.

PATIENT INFORMATION LEAFLET: INFORMATION FOR THE USER

GRAY 250 mg film-coated tablets

Levofloxacin
Generic medicine
Please read this leaflet carefully before taking this medicine as 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 could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What GRAY 250 mg is and what it is used for
What you need to know before taking GRAY 250 mg
How to take GRAY 250 mg
Possible side effects
How to store GRAY 250 mg
Contents of the pack and other information

1. What is GRAY 250 mg and what is it used for?

GRAY 250 mg is a broad-spectrum antibiotic, which means that GRAY 250 mg works by eliminating many types of bacteria that can cause infections (pathogens). GRAY 250 mg contains the active substance levofloxacin. This active substance belongs to a class of antibiotics called quinolones.
In adults with mild to moderate infections, GRAY 250 mg is used to treat infections against which the medicine is active, such as:

sinus infections
lung and lower respiratory tract infections: acute exacerbations of chronic bronchitis or pneumonia
urinary tract infections (both complicated and uncomplicated, e.g. involving the kidneys)
chronic bacterial prostatitis (prostate infection)
skin and soft tissue infections

2. What you need to know before taking GRAY 250 mg

Do NOT take GRAY 250 mg

if you are allergic (hypersensitive) to levofloxacin, to any excipient in GRAY 250 mg (see section 6), or to other quinolone antibiotics such as moxifloxacin, ciprofloxacin, or ofloxacin.
if you suffer from epilepsy
if you have a history of tendon problems related to treatment with a quinolone antibiotic
during pregnancy
during breastfeeding. These tablets must not be administered to children or growing adolescents.

Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine:

if you have experienced a severe skin reaction or skin peeling, blisters and/or mouth ulcers after taking any medicine containing levofloxacillin.
if you have been diagnosed with 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 or aortic dissection, congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome or Turner syndrome, Sjögren's syndrome [an autoimmune inflammatory disease], or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet’s disease, known high blood pressure or atherosclerosis, rheumatoid arthritis [an autoimmune inflammatory disease] or endocarditis [inflammation of the heart]).
You must not take quinolone/fluoroquinolone antibacterial medicines, including GRAY 250 mg, if you have previously had any serious adverse reaction during treatment with a quinolone or fluoroquinolone. In such cases, inform your doctor as soon as possible.
in severe cases of pneumonia caused by certain pathogens (e.g. S. pneumoniae). Consult your doctor, as GRAY 250 mg may not be the optimal therapy.
in hospital-acquired infections caused by certain pathogens (e.g. Pseudomonas aeruginosa). Consult your doctor, as these may require combination therapy.
in infections caused by certain pathogens (so-called MRSA). Consult your doctor, as these may require combination therapy.
if you develop severe, persistent and/or bloody diarrhoea during or after treatment with GRAY 250 mg. Inform your doctor immediately, as this diarrhoea may be a symptom of a serious intestinal inflammation (enterocolitis), which may occur following antibiotic treatment. Stop taking GRAY 250 mg. Your doctor will change your treatment. Do not take antidiarrhoeal medicines that slow intestinal movements. For this, consult your doctor or pharmacist.
if you are predisposed to seizures.

During treatment with GRAY 250 mg, the risk of epileptic seizures may be higher if you have previously suffered brain damage such as a stroke or severe head injury. You must inform your doctor if you have experienced such events. Do not take the tablets if you suffer from epilepsy.
The tendency to cramps may also be increased during concomitant treatment with fenbufen and other non-steroidal anti-inflammatory drugs (NSAIDs) used for pain and inflammation such as aspirin, ibuprofen, ketoprofen and indomethacin, or theophylline (see also “Use of other medicines”). If seizures occur, treatment must be discontinued.

if you suffer from glucose-6-phosphate dehydrogenase deficiency (an inherited metabolic disorder). Patients with this condition may be prone to destruction of red blood cells (haemolysis) when treated with quinolone antibacterial agents. Therefore, GRAY 250 mg should be used with caution in these patients.
if you have renal impairment. Ask your doctor how the dose should be adjusted (see section 3 “How to take GRAY 250 mg”).
if you experience severe allergic reactions (hypersensitivity) (sometimes after the initial dose). Seek immediate medical advice from your doctor or the nearest hospital. Discontinue treatment with GRAY 250 mg.
if you are taking oral hypoglycaemic agents (e.g. glibenclamide) or insulin. Your blood sugar levels must be closely monitored, as they may drop too low. Symptoms may include: excessive hunger, nervousness, sweating, trembling.
if you are exposed to strong sunlight or ultraviolet (UV) rays. Photosensitisation (hypersensitivity to light with sunburn-like reactions) is a rare event with levofloxacin. However, it is recommended to avoid unnecessary exposure to strong sunlight or artificial UV sources (e.g. sunlamps, solarium) to prevent photosensitisation.
if you are taking concomitantly a vitamin K antagonist (certain agents affecting blood clotting time, e.g. warfarin, phenprocoumon). Blood clotting times and bleeding tendency may increase. Blood clotting tests should be monitored (see also section “Use of other medicines”).
if you suffer from psychosis or have previously suffered from psychiatric illness. Psychotic reactions have been reported in patients treated with quinolones, including levofloxacin. In very rare cases, these may progress to suicidal thoughts and self-harming behaviour – sometimes after a single dose of levofloxacin. If such reactions occur, discontinue treatment and inform your doctor. Your doctor will decide on appropriate measures and further treatment.

Severe skin reactions
Serious skin reactions have been reported with levofloxacin use, 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 serious 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 as 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 attention.

Before taking Gray 250 mg

Heart problems Special caution is required when using this type of medicine if you were born with or have a family history of prolonged QT interval (seen on ECG, an electrical recording of the heart), have an electrolyte imbalance in the blood (especially low potassium or magnesium levels), have a very slow heart rate (bradycardia), have heart failure, have a history of heart attack (myocardial infarction), if you are female or elderly, or if you are taking other medicines that may cause abnormal changes on ECG (see section "Taking with other medicines").
if you have symptoms of nerve damage, such as sensory disturbances in hands and feet. In this case, consult your doctor immediately. Discontinue GRAY 250 mg to prevent possible damage.
if you are scheduled for a urine drug test for opiates. The test may give a false positive result. Confirmation of a positive result may be required using more specific methods.
if you have symptoms of liver disease, such as jaundice, dark urine, itching, loss of appetite (anorexia), or soft abdomen. Discontinue treatment with GRAY 250 mg and consult your doctor.
in cases of myasthenia gravis

During treatment with GRAY:

if you experience sudden, severe pain in the abdomen, chest, or back, 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 corticosteroids.
Inform your doctor immediately if you notice sudden 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).
If you develop sudden involuntary jerks, fasciculations, or muscle contractions – seek medical advice immediately, as these may be signs of myoclonus. Your doctor may need to discontinue levofloxacin treatment and start appropriate therapy.
If you develop nausea, general malaise, severe discomfort or persistent pain or worsening pain in the stomach area, or vomiting, contact your doctor immediately, as these may be signs of inflammation of the pancreas (acute pancreatitis).
If you experience fatigue, paleness of the skin, bruising, uncontrolled bleeding, fever, sore throat, and severe worsening of your general condition, or if you feel your resistance to infections has decreased – seek immediate medical advice, as these may be signs of blood disorders. Your doctor should monitor blood counts via complete blood count (CBC). If blood counts are abnormal, your doctor may discontinue treatment. Rarely, joint pain and swelling, and inflammation or rupture of tendons may occur. The risk is higher if you are elderly (over 60 years), have received an organ transplant, have kidney problems, or are taking corticosteroids. Tendon inflammation and rupture may occur within the first 48 hours of treatment and up to several months after stopping GRAY 250 mg. At the first signs of tendon pain or inflammation (e.g. in the ankle, wrist, elbow, shoulder, or knee), discontinue GRAY 250 mg, consult your doctor, and rest the affected area. Avoid unnecessary movement, 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, discontinue treatment with GRAY 250 mg and inform your doctor immediately to prevent permanent nerve damage. If your vision decreases or your eyes are otherwise affected, consult an ophthalmologist immediately. Serious, prolonged, disabling, and potentially irreversible adverse effects
Fluoroquinolone/quinolone antibacterial medicines, including GRAY 250 mg, have been associated with very rare but serious adverse effects, some of which are prolonged (lasting months or years), disabling, or may not improve. These include tendon, muscle, and joint pain in arms and legs, difficulty walking, abnormal sensations such as tingling, prickling, itching, numbness, or burning (paraesthesia), sensory organ disturbances such as changes in vision, taste, smell, or hearing, depression, memory impairment, severe fatigue, and severe sleep disturbances.
If you experience any of these adverse effects after taking GRAY 250 mg, contact your doctor immediately before continuing treatment. Your doctor will decide with you whether to continue treatment and may consider using an antibiotic from another class.

Children
Children or growing adolescents must not take GRAY 250 mg, as the risk of damage to joint tissues cannot be excluded.

Elderly
Renal impairment is common in this age group. Therefore, ask your doctor whether dose adjustment may be necessary (see section 3 “How to take GRAY 250 mg”).

Other medicines and GRAY 250 mg
You must inform your doctor if you are taking other medicines that may alter heart rhythm: medicines belonging to the antiarrhythmic class (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (macrolide class), and some antipsychotics.

Corticosteroids, sometimes called steroids – used for inflammation. You are more likely to develop tendon inflammation and/or tendon rupture.
Vitamin K antagonists, e.g. warfarin, phenprocoumon – used to thin the blood. The risk of bleeding increases. Your doctor may need regular blood tests to assess whether your blood is clotting properly.
Theophylline – used for respiratory problems: increases the risk of seizures if taken with GRAY 250 mg.
Non-steroidal anti-inflammatory drugs (NSAIDs) – used for pain and inflammation such as aspirin, ibuprofen, fenbufen, ketoprofen, and indomethacin: increases the risk of seizures if taken with GRAY 250 mg.
Cyclosporine – used after organ transplantation: the effect of cyclosporine may be prolonged when used in combination with GRAY 250 mg.
Probenecid – used for gout and cimetidine – used for ulcers and heartburn: the elimination (renal clearance) of levofloxacin is slightly reduced. However, this is unlikely to affect your treatment. Nevertheless, be cautious when taking GRAY 250 mg together with medicines such as probenecid and cimetidine, which affect renal elimination. If you have kidney problems, your doctor may prescribe a reduced dose.

Do not take GRAY 250 mg at the same time as the following medicines. This is because interactions with the mode of action of GRAY 250 mg may occur:

Iron tablets (for anaemia), zinc supplements, antacids containing magnesium or aluminium (for acidity or heartburn), didanosine, or sucralfate (for gastric ulcers). Therefore, take GRAY 250 mg at least 2 hours before or after taking these medicines.

Urine testing for opiates
Urine tests may show 'false positive' results for strong painkillers called 'opiates' in people taking GRAY 250 mg. If your doctor is planning to prescribe urine tests, inform them that you are taking GRAY 250 mg.

Tuberculosis testing
This medicine may cause 'false negative' results in certain laboratory tests that detect bacteria causing tuberculosis.

GRAY 250 mg with food, drinks and alcohol
Do not drink alcohol during treatment with GRAY 250 mg.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Do not take GRAY 250 mg if you are pregnant, trying to become pregnant, breastfeeding, or planning to breastfeed. Inform your doctor if you find you are pregnant while taking GRAY 250 mg.

Driving and using machines
Some adverse effects of GRAY 250 mg such as dizziness, drowsiness, and visual disturbances (see also section “4. Possible side effects”) may impair your ability to concentrate and react, and may therefore pose a risk in situations where these abilities are particularly important. Do not drive, operate machinery, or perform activities without secure support if you notice these abilities are impaired. Exercise particular caution when consuming alcohol.

Gray contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take GRAY 250 mg

Take this medicine exactly as instructed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
Recommended dose: see Table 1

Table 1: Dosage in patients with normal renal function
Sinusitis (infection of the paranasal sinuses):	2 film-coated GRAY 250 mg tablets once daily (equivalent to 500 mg of levofloxacin).
Acute exacerbation of chronic bronchitis (lung infection in people with long-term respiratory problems):	from 1 film-coated GRAY 250 mg tablet (equivalent to 250 mg of levofloxacin) to 2 film-coated GRAY 250 mg tablets (equivalent to 500 mg of levofloxacin) once daily.
Pneumonia:	2 film-coated GRAY 250 mg tablets once or twice daily (equivalent to 500 or 1000 mg of levofloxacin).
Urinary tract infections:	1 film-coated GRAY 250 mg tablet once daily (equivalent to 250 mg of levofloxacin).
Chronic bacterial prostatitis:	2 film-coated GRAY 250 mg tablets once daily (equivalent to 500 mg of levofloxacin).
Skin and soft tissue infections:	from 1 film-coated GRAY 250 mg tablet once daily (equivalent to 250 mg of levofloxacin) to 2 film-coated GRAY 250 mg tablets once or twice daily (equivalent to 500 or 1000 mg of levofloxacin).

Since levofloxacin is primarily excreted by the kidneys, the dose must be adjusted in patients with impaired renal function. For details, refer to Table 2 below:

Table 2: Dosing in patients with reduced renal function
Dosing regimen
250 mg/24 hours 500 mg/24 hours 500 mg/12 hours
Creatinine clearance First dose: 250 mg First dose: 500 mg First dose: 500 mg
50 – 20 ml/min then: 125 mg/24 hours then: 250 mg/24 hours then: 250 mg/12 hours
19 – 10 ml/min then: 125 mg/48 hours then: 125 mg/24 hours then: 125 mg/12 hours
<10 ml/min (including hemodialysis and then: 125 mg/48 hours then: 125 mg/24 hours then: 125 mg/24 hours
CAPD)
= No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

No dose adjustment is necessary if you have impaired liver function. Levofloxacin is only minimally metabolized in the liver.

How to take this medicine
Swallow the film-coated tablets whole without chewing, with an adequate amount of liquid (e.g., ½ to 1 glass of water). If you need to adjust the dose, you may break the film-coated tablets along the break line. You may take the film-coated tablets during meals or at any time between meals.
See also section “Other medicines and GRAY 250 mg”.

Duration of treatment
The duration of treatment will depend on the severity of your infection. Your doctor will determine the optimal duration of treatment.
If you notice that the effect of GRAY 250 mg is too strong or too weak, inform your doctor or pharmacist.

If you take more GRAY 250 mg than you should
If you accidentally take one extra film-coated tablet of GRAY 250 mg, probably nothing serious will happen. However, if you accidentally take several extra film-coated tablets, contact your doctor immediately. You may experience the following symptoms:

central nervous system symptoms (confusion, dizziness, reduced level of consciousness, and epileptic seizures)
gastrointestinal reactions such as nausea and mucosal erosions
certain changes in cardiac function (prolongation of the QT interval). Therefore, your cardiac function should be monitored by your doctor (ECG) in case of overdose. Your doctor will initiate treatment according to your symptoms (e.g., gastric lavage or administration of antacids). Levofloxacin is not removed from the body by dialysis. There is no specific antidote.

If you forget to take GRAY 250 mg
Take the missed dose as soon as you remember, unless it is almost time for your next scheduled dose. In that case, continue taking GRAY 250 mg at your usual time and at the dose prescribed by your doctor. Do not take a double dose to make up for the missed tablet.

If you stop taking GRAY 250 mg
Do not stop taking GRAY 250 mg without approval from your doctor. Treatment may fail if you stop too early.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

The assessment of the frequency of side effects is based on the following classification:

Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Frequency not known: frequency cannot be estimated from the available data

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

Stop taking GRAY and go immediately to a doctor or hospital if you notice the following side effect:

Very rare

You have an allergic reaction. Signs may include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue

Stop taking GRAY and go immediately to a doctor if you notice any of the following side effects – you may need urgent medical treatment:

Rare

Watery diarrhoea, possibly with blood, sometimes accompanied by stomach cramps and high fever. This may be a sign of a serious intestinal problem
Pain and inflammation of tendons or ligaments, which in some cases may rupture. The Achilles tendon is most commonly affected
Seizures
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)

Very rare

Burning, tingling, pain or numbness. These signs may indicate a condition called "neuropathy"

Not known

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 stomach pain. These may be signs of liver problems, including potentially fatal liver failure (liver failure that can lead to death).
Nausea, general feeling of illness, discomfort or pain in the stomach area, or vomiting. These may be signs of inflammation of the pancreas (acute pancreatitis). See section 2.

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

Inform your doctor if any of the following side effects worsen or last longer than a few days:

Common

Difficulty sleeping
Headache, dizziness
Frequent, watery bowel movements (diarrhoea), feeling unwell (nausea, vomiting)
Increased levels in the blood of certain liver enzymes

Uncommon

Changes in the number of other bacteria or fungi, fungal infection called Candida, which may require treatment
Decrease in the number of white blood cells (leukopenia), increase in the number of certain blood cells (eosinophilia)
Feeling stressed (anxiety), confusion, nervousness, drowsiness, tremor, dizziness
Shortness of breath (dyspnoea)
Change in taste, loss of appetite, stomach discomfort or indigestion (dyspepsia), stomach pain, bloating (flatulence), constipation
Signs of reduced kidney function (elevated blood creatinine levels)
Itching and skin rash, severe itching or hives, excessive sweating (hyperhidrosis)
Joint pain or muscle pain
Generalised weakness
Signs of reduced liver function (elevated blood bilirubin levels)

Rare

Fast heartbeat (tachycardia)
Decrease in the number of blood platelets (thrombocytopenia), leading to a tendency to bruise and bleed
Decrease in the number of certain white blood cells (neutropenia)
Exaggerated immune response (hypersensitivity)
Decreased blood sugar levels (hypoglycaemia). This is important for people with diabetes
Seeing or hearing things that are not there (hallucinations, paranoia), changes in thinking and second thoughts (psychotic reactions), with possible development of suicidal thoughts or suicide attempts
Feeling depressed, mental problems, feeling restless (agitation), unusual dreams or nightmares
Tingling sensation in hands and feet (paraesthesia)
Hearing problems (tinnitus) or vision problems (blurred vision)
Drop in blood pressure
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 in the kidneys called interstitial nephritis
Fever
Clearly defined erythematous spots, with or without blister formation, developing within a few hours of levofloxacin administration and healing with redness; these usually recur at the same skin or mucosal site after subsequent exposure to levofloxacin

Frequency not known:

Heart problems: abnormally fast heart rate, life-threatening irregular heart rhythm, changes in heart rhythm (called QT interval prolongation, seen on ECG, the heart's electrical activity)
Decrease in the number of all types of blood cells (pancytopenia); decrease in red blood cells due to damage to blood cells (haemolytic anaemia)
The bone marrow stops producing new blood cells, which may cause fatigue, reduced ability to fight infections and uncontrolled bleeding (bone marrow failure)
Severe decrease in certain white blood cells (agranulocytosis). This leads to severe symptoms (persistent or recurring fever, sore throat and worsening general condition)
Anaphylactic shock (severe hypersensitivity reaction, see section "Take special care with GRAY 250 mg"). Anaphylactic and hypersensitivity reactions may sometimes occur even after the first dose
Increased blood sugar levels (hyperglycaemia) or decreased blood sugar levels leading to coma (hypoglycaemic coma). This is important for people with diabetes
Change in the smell of things, loss of smell or taste (parosmia, anosmia, ageusia)
Feeling very excited, euphoric, agitated or enthusiastic (mania)
Difficulty in moving and walking (dyskinesia, extrapyramidal disorders)
Temporary loss of consciousness or posture (syncope)
Temporary loss of vision, eye inflammation
Worsening or loss of hearing
Difficulty breathing or wheezing (bronchospasm)
Allergic reactions affecting the lungs
Pancreatitis
Inflammation of the liver (hepatitis)
Increased sensitivity of the skin to sunlight or ultraviolet rays (photosensitivity), darker areas of skin (hyperpigmentation)
Inflammation of the blood vessels carrying blood throughout the body due to an allergic reaction (vasculitis)
Inflammation of the internal tissues of the mouth (stomatitis)
Muscle damage (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 have porphyria (a very rare metabolic disorder)
Persistent headache with or without blurred vision (benign intracranial hypertension)

Very rare cases of adverse drug reactions that are prolonged (lasting for months or years) or permanent, such as tendon inflammation, tendon rupture, joint pain, pain in arms or legs, difficulty walking, abnormal sensations such as pricking, tingling, itching, burning, numbness or pain (neuropathy), fatigue, memory and concentration problems, mental health effects (which may include sleep disorders, anxiety, panic attacks, depression and suicidal thoughts), as well as hearing, vision, taste and smell disturbances, have been associated with the use of quinolone and fluoroquinolone antibiotics, in some cases regardless of pre-existing risk factors.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

Contact your doctor immediately if a side effect appears suddenly or worsens rapidly, as certain adverse drug reactions (e.g. pseudomembranous colitis, certain blood abnormalities, severe anaphylactic or anaphylactoid reactions, severe liver disorders and severe skin reactions) may be life-threatening. In such cases, do not continue taking the medicine without medical advice.

5. How to store GRAY 250 mg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp.".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions; however, it is preferable to
store GRAY 250 mg in its original blister and packaging, in a dry place.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What GRAY 250 mg contains
The active substance is levofloxacin. Each tablet of GRAY 250 mg contains 250 mg of
levofloxacin.
The other components are:

For the tablet core: crospovidone, hypromellose, microcrystalline cellulose and sodium stearyl fumarate
For the coating: hypromellose, titanium dioxide (E171), talc, macrogol, yellow iron oxide (E172) and red iron oxide (E172).

Description of the appearance of GRAY 250 mg and package contents
Film-coated tablets for oral use. The tablets are oblong and have a pale yellow-white to reddish-white break line.
GRAY 250 mg tablets are available in packs containing 5 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Aurora Biofarma S.r.l. Via Nicola Antonio Porpora 127, 20131 Milano, Italy

Manufacturer
DOPPEL FARMACEUTICI SRL
Via Volturno, 48 – 20089 Quinto de' Stampi – Rozzano (MI)
DOPPEL FARMACEUTICI SRL
Via Martiri delle Foibe, 1 – 29016 Cortemaggiore (PC)
(batch control and release)

This patient information leaflet does not include all available information on this medicine. If you need further information or have any questions, please consult your doctor or pharmacist.