Patient Information Leaflet

Xyvelam, 250 mg, film-coated tablets
Xyvelam, 500 mg, film-coated tablets
Levofloxacinum
Please read all of 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 further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Xyvelam is and what it is used for

The name of this medicine is Xyvelam. Xyvelam contains an active substance called levofloxacin, which belongs to a group of medicines known as antibiotics. Levofloxacin is a "quinolone" antibiotic. It works by killing bacteria that cause infections in the body.
Xyvelam may be used to treat certain infections

sinus infections
lung infections in patients with chronic respiratory problems or pneumonia
urinary tract infections, including infections of the kidneys or bladder
prostate gland infections, in cases of long-term inflammation
skin and subcutaneous tissue infections, including muscles; sometimes referred to as "soft tissue"

In certain exceptional situations, Xyvelam may be used to treat or prevent a lung disease called anthrax that may develop after exposure to the bacteria that cause anthrax.

2. Important information before using Xyvelam

When not to use Xyvelam

if the patient is allergic to levofloxacin, any other quinolone antibiotic such as moxifloxacin, ciprofloxacin or ofloxacin, or to any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
if the patient has ever had seizures
if the patient has ever had tendon problems (e.g. tendonitis) associated with treatment with antibiotics of the so-called "quinolone" group. A tendon is a band of fibres connecting muscles to bones.
if the medicine has been prescribed for a child or adolescent during the growth period
if the patient is pregnant, may become pregnant, or suspects she may be pregnant
if the patient is breastfeeding

Do not take this medicine if any of the above statements apply to the patient.
If in doubt, talk to your doctor or pharmacist before starting to take Xyvelam.
Warnings and precautions
Before starting treatment with Xyvelam, discuss this with your doctor or pharmacist if:

the patient is 60 years of age or older
the patient is taking corticosteroids, sometimes called steroids (see section "Xyvelam and other medicines")
the patient has received an organ transplant
the patient has ever had seizures (epileptic fits)
the patient has had brain damage due to stroke or other injury
the patient has kidney problems
the patient has a condition called "glucose-6-phosphate dehydrogenase deficiency"; the patient may then be more susceptible to serious blood disorders during treatment with this medicine
the patient has ever had mental health problems
the patient has ever had heart problems: caution is needed during treatment with this medicine if the patient has a congenital or familial history of QT interval prolongation (seen on ECG, i.e. a test of the heart's electrical activity), has electrolyte imbalances in the blood (especially low potassium or magnesium levels), has a slow heart rate (called "bradycardia"), has impaired heart function (heart failure), has previously had a heart attack (myocardial infarction), is female or elderly, or is taking other medicines causing unusual changes in the ECG (see section "Xyvelam and other medicines")
the patient has diabetes
the patient has ever had liver problems
the patient has myasthenia gravis
the patient has nerve damage (peripheral neuropathy)
the patient has been diagnosed with a dilated large blood vessel (aortic aneurysm or large peripheral artery aneurysm)
the patient has previously experienced aortic dissection (tearing of the aortic wall)
the patient has been diagnosed with heart valve regurgitation
in the family there have been cases of aortic aneurysm or aortic dissection, or congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Sjögren's syndrome [an autoimmune inflammatory disease], or vascular diseases such as Takayasu arteritis, giant cell arteritis, Behçet's disease, hypertension, or confirmed arterial atherosclerosis, or rheumatoid arthritis [joint disease], or endocarditis [heart infection])
the patient has ever experienced severe skin rash, skin peeling, blistering and (or) oral mucosal ulcers after taking levofloxacin

If the patient is unsure whether any of the above statements apply, they should talk to their doctor or pharmacist before starting treatment with Xyvelam.
Severe skin reactions
Severe skin reactions have been reported during treatment with levofloxacin, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS).

SJS or TEN may initially appear as red, target-like or circular spots, often with blisters in the centre, on the trunk. Oral, throat, nasal, genital and ocular ulcers (red and swollen eyes) may also occur. These severe rashes are often preceded by fever and (or) flu-like symptoms. These rashes may lead to extensive skin peeling, which may be life-threatening or fatal.
In DRESS syndrome, flu-like symptoms and facial rash occur initially, followed by widespread rash with high fever, increased liver enzyme activity and increased white blood cell count (eosinophilia) in blood tests, and enlarged lymph nodes.

If a severe rash or any of these skin symptoms occur, stop taking levofloxacin immediately and contact your doctor or seek urgent medical help.
Do not take antibacterial medicines containing fluoroquinolones or quinolones, including levofloxacin, if the patient has previously experienced any severe adverse reaction while taking a quinolone or fluoroquinolone. In such a case, inform your doctor as soon as possible.
While taking Xyvelam

if sudden severe abdominal, back or chest pain occurs, which may be a sign of an aneurysm or aortic dissection, seek emergency department care immediately. The risk of these events may be higher when undergoing systemic corticosteroid treatment.
if sudden shortness of breath occurs, especially when lying down, or if ankle, foot or abdominal swelling or palpitations (sensation of rapid or irregular heartbeat) are observed, seek medical advice immediately
if sudden, involuntary muscle jerks, tremors or muscle cramps occur, contact your doctor immediately, as these may be symptoms of myoclonus. Your doctor may decide to discontinue levofloxacin and initiate appropriate treatment.
if nausea, general malaise, intense discomfort or persistent or worsening abdominal pain or vomiting occur, contact your doctor immediately, as these may be symptoms of pancreatitis (acute inflammation of the pancreas)
if fatigue, pale skin, bruising, uncontrolled bleeding, fever, sore throat and significant worsening of health or a feeling of reduced immunity to infections occur, contact your doctor immediately, as these may be symptoms of blood disorders. Your doctor should monitor the patient's blood picture with a complete blood count. If abnormalities in blood counts occur, the doctor may decide to discontinue treatment.

Rarely, tendon pain and swelling, inflammation or rupture may occur. The risk is increased in elderly patients (over 60 years), after organ transplantation, in patients with kidney problems or those receiving corticosteroid treatment. Tendon inflammation and rupture may occur within the first 48 hours of treatment, and even up to several months after discontinuation of Xyvelam. After the first symptoms of tendon pain or inflammation (e.g. in the ankle, wrist, elbow, shoulder or knee), stop taking Xyvelam, contact your doctor and rest the affected area. Avoid excessive physical exertion, as this may increase the risk of tendon rupture.
The patient may rarely experience symptoms of nerve damage (neuropathy), such as pain, burning, tingling, numbness and (or) weakness, especially in the feet and legs and hands and arms. In such a case, stop taking Xyvelam and inform your doctor immediately to prevent the development of potentially irreversible disease.
Long-term, disabling and potentially irreversible serious adverse effects
Antibacterial medicines containing fluoroquinolones and (or) quinolones, including Xyvelam, have been associated with very rare but serious adverse effects. Some of these were long-term (lasting for months or years), disabling or potentially irreversible. These include: tendon, muscle and joint pain in the upper and lower limbs, difficulty walking, abnormal sensations such as pricking, tingling, tickling, numbness or burning (paresthesia), sensory disturbances, including vision, taste, smell and hearing disturbances, depression, memory problems, severe fatigue and severe sleep disturbances.
If any of these adverse effects occur after taking Xyvelam, contact your doctor immediately before continuing treatment. The patient and doctor will decide whether to continue treatment, also considering antibiotics from other classes.
If in doubt whether any of the above situations apply to the patient, consult your doctor or pharmacist before using Xyvelam.
Xyvelam and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This is because Xyvelam may affect the action of other medicines, and other medicines may affect the action of Xyvelam.
In particular, inform your doctor if the patient is taking any of the following medicines, as the risk of adverse effects may increase when used concomitantly with Xyvelam:

corticosteroids, sometimes called steroids – used for inflammatory conditions. The patient may be more susceptible to tendon inflammation and (or) damage.
warfarin – used to thin the blood. The patient may be more susceptible to bleeding. Your doctor may order regular blood tests to monitor blood clotting.
theophylline – used for breathing problems. The patient may be more susceptible to seizures (epileptic fits) when taking Xyvelam.
non-steroidal anti-inflammatory drugs (NSAIDs) – used to treat pain and inflammation, such as: acetylsalicylic acid, ibuprofen, fenbufen, ketoprofen, indometacin. The patient may be more susceptible to seizures (epileptic fits) when taking Xyvelam.
cyclosporine – used after organ transplantation. The patient may be more susceptible to cyclosporine adverse effects.
medicines affecting heart rhythm. This includes medicines used for irregular heartbeat (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 to treat gout. The treating doctor may recommend a lower dose if the patient has kidney problems.
cimetidine – used to treat peptic ulcer disease and heartburn. The treating doctor may recommend a lower dose if the patient has kidney problems.

If any of the above apply to the patient, inform your doctor.
Do not take Xyvelam at the same time as the following medicines, as they may affect its effectiveness:

iron-containing tablets (used for anaemia), zinc supplements, antacids containing magnesium or aluminium (used for hyperacidity or heartburn), didanosine or sucralfate (used for stomach ulcers) (see section 3 "If the patient is already taking iron-containing tablets, zinc supplements, antacids, didanosine or sucralfate")

Urine tests detecting opioids
Urine tests detecting strong painkillers called opioids may give false positive results in patients taking Xyvelam. If your doctor recommends a urine test, inform them that you are taking Xyvelam.
Tests detecting tuberculosis
This medicine may cause false negative results in certain laboratory tests used to detect tuberculosis-causing bacteria.
Pregnancy and breastfeeding
Do not use this medicine if the patient:

is pregnant, may become pregnant, or suspects she may be pregnant
is breastfeeding or plans to breastfeed

Driving and operating machinery
After taking this medicine, the patient may experience adverse effects, including dizziness, drowsiness, vertigo or visual disturbances. Some of these adverse effects may impair concentration and reaction speed. In such a case, the patient should not drive or operate machinery requiring concentration.
Xyvelam contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before starting treatment with Xyvelam.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Xyvelam

This medicine should always be taken as directed by the doctor. If in doubt, consult the doctor or pharmacist.

Taking the medicine

The medicine should be taken orally.
Swallow the tablet whole with water.
Tablets may be taken during or between meals.

If the patient is already taking iron-containing tablets, zinc preparations, antacids, didanosine, or sucralfate

Do not take these medicines at the same time as Xyvelam. The prescribed dose should be taken at least 2 hours before or 2 hours after taking Xyvelam tablets.

Recommended dose

The doctor will decide how many Xyvelam tablets the patient should take.
The dose depends on the type and location of the infection.
The duration of treatment depends on the severity of the infection.
If the patient feels the effect of the medicine is too weak or too strong, the dose should not be changed without consulting the doctor.

Adults and elderly patients
Sinusitis

two Xyvelam 250 mg tablets once daily, or
one Xyvelam 500 mg tablet once daily

Lung infections in patients with chronic breathing problems

two Xyvelam 250 mg tablets once daily, or
one Xyvelam 500 mg tablet once daily

Pneumonia

two Xyvelam 250 mg tablets once or twice daily, or
one Xyvelam 500 mg tablet once or twice daily

Urinary tract infections, including kidneys or bladder

one or two Xyvelam 250 mg tablets once daily, or
half or one Xyvelam 500 mg tablet once daily

Prostate gland infections

two Xyvelam 250 mg tablets once daily, or
one Xyvelam 500 mg tablet once daily

Skin and subcutaneous tissue infections, including muscles

two Xyvelam 250 mg tablets once or twice daily, or
one Xyvelam 500 mg tablet once or twice daily

Exposure to inhaled anthrax bacteria

two Xyvelam 250 mg tablets once daily, or
one Xyvelam 500 mg tablet once daily

Adults and elderly patients with impaired kidney function
The doctor may recommend a lower dose.

Use in children and adolescents
This medicine should not be used in children and adolescents.

Skin protection from sunlight
During treatment with this medicine and for 2 days after stopping it, avoid direct sunlight exposure. This is because the skin becomes more sensitive to sunlight, which may lead to sunburn, tingling sensation, and large blisters if the following precautions are not taken:

Use sunscreen creams with a high UV protection factor
Always wear a hat and clothing covering arms and legs
Avoid using sunbeds (solariums)

Taking more Xyvelam than recommended
If more tablets than recommended are accidentally taken, contact a doctor or seek medical help immediately. Bring the medicine packaging along so the doctor knows which medicine has been taken. The following symptoms may occur: seizures (epileptic fits), confusion, dizziness, disturbances of consciousness, muscle tremors, heart disturbances leading to irregular heartbeat, as well as nausea and heartburn.

Missing a dose of Xyvelam
If a dose of Xyvelam is missed, take it as soon as possible unless the next dose is due soon. Do not take a double dose to make up for the missed dose.

Stopping Xyvelam treatment
Do not stop taking Xyvelam just because the patient feels better. It is important to take all the tablets prescribed by the doctor. Stopping treatment too early may cause the infection to return, worsen the patient's condition, or lead to bacteria becoming resistant to the medicine.

If there are any further doubts about using this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Discontinue use of Xyvelam and seek immediate medical attention or go to hospital if the patient experiences
any of the following adverse reactions:
Very rare (may occur in fewer than 1 in 10,000 patients)

allergic reaction. Symptoms may include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.

Discontinue use of Xyvelam and contact a doctor immediately if the patient experiences
any of the following adverse reactions – immediate treatment may be required.
Rare (may occur in fewer than 1 in 1,000 patients)

watery diarrhoea, which may contain blood, possibly accompanied by stomach cramps and high fever. These may be symptoms of serious intestinal problems.
pain and inflammation of tendons or ligaments, potentially leading to tendon rupture. Most commonly affects the Achilles tendon.
seizures (epileptic fits)
seeing or hearing things that are not real (hallucinations, paranoia)
feelings of depression, psychiatric disturbances, anxiety (agitation), strange dreams or nightmares
widespread rash, high body temperature, increased liver enzyme activity, abnormal blood counts (eosinophilia), swollen lymph nodes and other organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome). See also section 2.
syndrome associated with impaired water excretion and low sodium levels (SIADH)
decreased blood sugar levels (hypoglycaemia) or hypoglycaemia leading to coma (hypoglycaemic coma). This is important in diabetic patients.

Very rare (may occur in fewer than 1 in 10,000 patients)

burning, tingling, pain or numbness; these may be symptoms of "neuropathy"

Frequency not known (frequency cannot be estimated from available data)

severe skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red, target-like or circular spots, often with central blisters on the trunk, 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 whites of the eyes, dark urine, itching, stomach tenderness (abdominal tenderness). These may be symptoms of liver dysfunction, including fatal liver damage.
changes in thinking and thoughts (psychotic reactions) with risk of suicidal thoughts or attempts
nausea, general malaise, discomfort or pain in the abdomen, or vomiting. These may be symptoms of pancreatitis (acute pancreatitis). See section 2.

If vision deteriorates or other visual disturbances occur during treatment with
Xyvelam, contact an ophthalmologist immediately.
Administration of quinolone and fluoroquinolone antibiotics has, in some cases regardless of pre-existing risk factors, very rarely led to long-term (lasting for months or even years) or permanent adverse reactions such as: tendon inflammation, tendon rupture, joint pain, limb pain, difficulty walking, abnormal sensations such as pricking, tingling, tickling, burning, numbness or pain (neuropathy), fatigue, memory and concentration problems, mental health disturbances (which may include: sleep disturbances, anxiety, panic attacks, depression and suicidal thoughts), as well as disturbances in hearing, vision, taste and smell.
In patients receiving fluoroquinolones, cases of arterial wall dilation and weakening or arterial wall rupture (aneurysm and dissection) have been reported, which may result in rupture and lead to death, as well as cases of heart valve insufficiency. See also section 2.
Contact a doctor if any of the following adverse reactions worsen or persist for longer than a few days.
Common (may occur in fewer than 1 in 10 patients)

sleep disturbances
headache, dizziness
nausea, vomiting and diarrhoea
increased activity of certain liver enzymes in the blood

Uncommon (may occur in fewer than 1 in 100 patients)

changes in the number of certain types of bacteria or fungi, Candida fungal infection, which may require treatment
changes in white blood cell count, visible in certain blood tests (leukopenia, eosinophilia)
anxiety, confusion, nervousness, drowsiness, tremors, sensation of spinning (dizziness)
shortness of breath (dyspnoea)
altered taste perception, loss of appetite, stomach disturbances or indigestion, stomach pain, bloating with flatulence or constipation
itching and skin rash, severe itching or urticaria, excessive sweating
joint or muscle pain
abnormal blood test results due to impaired liver function (increased bilirubin levels) or kidney function (increased creatinine levels)
general weakness

Rare (may occur in fewer than 1 in 1,000 patients)

increased tendency to bruising and bleeding due to reduced platelet count (thrombocytopenia)
low white blood cell count (neutropenia)
excessive immune response (hypersensitivity)
tingling sensation in hands and feet (paresthesia)
hearing problems (tinnitus) or vision problems (blurred vision)
abnormally rapid heartbeat (tachycardia) or low blood pressure (hypotension)
reduced muscle strength – this is important in patients with myasthenia gravis (a rare neurological disorder)
changes in kidney function and sometimes kidney failure, possibly due to an allergic reaction in the kidneys known as interstitial nephritis
fever
sharply defined, erythematous patches with or without blisters, developing within hours after administration of levofloxacin. These resolve with post-inflammatory pigmentation. Upon subsequent administration of levofloxacin, these lesions usually reappear at the same site on the skin or mucous membranes.
memory disturbances

Frequency not known (frequency cannot be estimated from available data)

decreased number of red blood cells (anaemia): this may cause paleness or yellowing of the skin due to destruction of red blood cells; decreased number of all blood cell types (pancytopenia)
cessation of new blood cell production by the bone marrow, which may lead to fatigue, reduced ability to fight infections and uncontrolled bleeding (bone marrow failure)
fever, sore throat and persistent general malaise. This may be due to reduced white blood cell count (agranulocytosis).
circulatory collapse (anaphylactoid shock)
increased blood sugar levels (hyperglycaemia) – this is important in diabetic patients
changes in smell, loss of smell or taste (olfactory hallucinations, anosmia, ageusia)
intense feeling of excitement, elation, agitation or enthusiasm (mania)
problems with movement and walking (dyskinesia, extrapyramidal disorders)
transient loss of consciousness or fainting (syncope)
transient loss of vision, eye inflammation
hearing disturbances or hearing loss
abnormally fast heart rhythm, life-threatening irregular heartbeat, including cardiac arrest, changes in heart rhythm (so-called "QT prolongation" visible on ECG, i.e. test of the heart's electrical activity)
difficulty breathing or wheezing (bronchospasm)
allergic reactions affecting the lungs
pancreatitis
hepatitis
increased skin sensitivity to sunlight and ultraviolet radiation (photosensitivity), skin discolouration (hyperpigmentation)
inflammation of blood vessels due to allergic reaction (vasculitis)
inflammation of the lining of the mouth (oral mucositis)
muscle breakdown and disintegration (rhabdomyolysis)
redness and swelling of joints (arthritis)
pain, including back, chest and limb pain
sudden, involuntary jerks, muscle twitches and muscle spasms (myoclonus)
porphyria attacks in patients with porphyria (a very rare metabolic disorder)
persistent headache with blurred vision (benign intracranial hypertension)

Reporting of adverse reactions
If any adverse symptoms occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the local representative of the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Xyvelam

Keep this medicine out of sight and reach of children.
No special storage conditions apply for this medicine.
Do not use this medicine after the expiry date stated on the carton and blister after "EXP".
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Xyvelam contains

The active substance is levofloxacin.

Xyvelam, 250 mg, film-coated tablets
Each film-coated tablet contains 250 mg of levofloxacin as levofloxacin hemihydrate (256.23 mg).
Xyvelam, 500 mg, film-coated tablets
Each film-coated tablet contains 500 mg of levofloxacin as levofloxacin hemihydrate (512.46 mg).

Other ingredients are:
- tablet core: sodium stearyl fumarate, crospovidone type A, colloidal anhydrous silica, copovidone, microcrystalline cellulose silicified (98% microcrystalline cellulose and 2% colloidal anhydrous silica)
- tablet coating: Opadry II Pink 31K34554 [lactose monohydrate, hypromellose 15 cP, titanium dioxide (E 171), triacetin, iron oxide red (E 172), iron oxide yellow (E 172)]

What Xyvelam looks like and contents of the pack
Xyvelam, 250 mg, film-coated tablets
Pink, biconvex tablets, with a score line on one side and the mark "L" on the other side. The length is approximately 13 mm and the width 6 mm. The tablet can be divided into equal doses.
Xyvelam, 500 mg, film-coated tablets
Pink, biconvex tablets, with a score line on one side and the mark "L" on the other side. The length is approximately 16 mm and the width 8 mm. The tablet can be divided into equal doses.

Pack sizes
Aluminium/PVC blisters containing 5, 7, 10 or 14 film-coated tablets, in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
+pharma arzneimittel gmbh
Hafnerstraße 211
8054 Graz, Austria

Manufacturer
Actavis Ltd.
BLB015-016, Bulebel Industrial Estate
Zejtun ZTN3000, Malta

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
+pharma Polska sp. z o.o.
ul. Podgórska 34
31-536 Kraków, Poland
tel: +48 12 262 32 36
e-mail: [email protected]