LEVOFLOXACIN AUROVITAS 5 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you use Levofloxacino Aurovitas Solution for Infusion

Do not use Levofloxacino Aurovitas Solution for Infusion

• If you are allergic to levofloxacin, other quinolone antibiotics such as moxifloxacin, ciprofloxacin, or ofloxacin, or any of the other ingredients of this medicine (listed in section 6).
• Signs of an allergic reaction include: skin 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 tendonitis, related to the use of quinolone medicines. The tendon is the tissue that connects your muscle to your skeleton.
• If you are a child or adolescent in the growth phase.
• If you are pregnant, may become pregnant, or think you may be pregnant.
• If you are breastfeeding or plan to breastfeed.

Do not use this medicine if any of the above cases apply to you. If in doubt, consult your doctor, nurse, or pharmacist before using levofloxacin solution for infusion.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before using Levofloxacino Aurovitas Solution for Infusion if:

• You have ever developed a severe skin rash, skin peeling, blisters, and/or mouth sores after taking levofloxacin.
• You are 60 years or older.
• You are taking corticosteroids, sometimes called steroids (see section "Other medicines and Levofloxacino Aurovitas Solution for Infusion").
• You have received a transplant.
• You have had a seizure (convulsions).
• You have had brain damage due to a stroke or other brain injury.
• You have kidney problems.
• You have what is known as "glucose-6-phosphate dehydrogenase deficiency", as you may be prone to having serious blood problems when taking this medicine.
• You have had mental health problems.
• You have ever had heart problems: caution should be exercised when using this type of medicine if you were born with, or have a family history of, prolonged QT interval (seen on an electrocardiogram (ECG), a graphical representation of the heart's electrical activity), have an imbalance in blood salt levels (especially low potassium or magnesium levels in the blood), have a slow heart rate (bradycardia), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), if you are a woman or an elderly person, or are taking other medicines that may cause abnormal changes in the ECG (see section "Other medicines and Levofloxacino Aurovitas Solution for Infusion").
• You are diabetic.
• You have ever had liver problems.
• You have myasthenia gravis.
• You have peripheral nerve disorder (peripheral neuropathy).
• You have been diagnosed with an aneurysm of a large blood vessel (aortic aneurysm or large peripheral vessel aneurysm).
• You have had a previous episode of aortic dissection (tear in the aortic wall).
• You have been diagnosed with heart valve insufficiency (regurgitation of the heart valves).
• You have a family history of aortic aneurysm or aortic dissection, congenital heart valve disease, or other risk factors or predisposing disorders (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, or Sjögren's syndrome (an autoimmune inflammatory disease), or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behçet's disease, hypertension, or atherosclerosis, or rheumatoid arthritis (a joint disease) or endocarditis (a heart infection)).

Quinolone antibiotics may cause an increase in your blood sugar levels above normal levels (hyperglycemia) or a decrease in your blood sugar levels below normal levels, which in severe cases can lead to loss of consciousness (hypoglycemic coma) (see section 4). This is important for people with diabetes. If you have diabetes, your blood sugar levels should be carefully monitored.

Severe Skin Reactions

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

• SJS/TEN may initially appear as red, target-like spots or circular patches on the trunk, often with blisters in the center. They may also appear as ulcers in the mouth, throat, nose, genitals, and eyes (red and swollen eyes). These severe skin rashes are often preceded by fever and/or flu-like symptoms. The rashes can progress to widespread skin peeling and life-threatening complications.
• DRESS is initially manifested by flu-like symptoms and a rash on the face, followed by a more widespread rash with elevated body temperature, elevated liver enzymes observed in blood tests, and an increase in a type of white blood cell (eosinophilia) and swollen lymph nodes.

If you develop a severe rash or any of these skin symptoms, stop using levofloxacin and contact your doctor or seek medical attention immediately.

Before You Start Using This Medicine

Do not take antibacterial medicines that contain fluoroquinolones or quinolones, including levofloxacin, if you have experienced any severe side effects in the past when taking a quinolone or fluoroquinolone. If this applies to you, inform your doctor as soon as possible.

Consult Your Doctor, Pharmacist, or Nurse During Treatment with Your Medicine:

• If you experience severe and sudden pain in the abdomen, chest, or back, which can be symptoms of aortic dissection or aneurysm, go to the emergency room immediately. The risk may increase if you are receiving systemic corticosteroid treatment.
• If you start experiencing sudden shortness of breath, especially when lying down, or if you notice swelling in your ankles, feet, or abdomen, or the appearance of heart palpitations (feeling of rapid or irregular heartbeat), inform your doctor immediately.
• If you have nausea, general discomfort, have intense discomfort or ongoing pain in the stomach area, or vomit - consult a doctor immediately, as this could be a sign of pancreatitis (inflammation of the pancreas).

Consult an ophthalmologist immediately if you experience any changes in your vision or have any eye problems.

During Treatment with This Medicine

Rarely, pain and swelling in the joints and inflammation or rupture of the tendons can occur. The risk is greater if you are an elderly person (over 60 years), have received an organ transplant, have kidney problems, or are being treated with corticosteroids. Tendon inflammation and rupture can occur within the first 48 hours of treatment and even several months after stopping treatment with levofloxacin. At the first sign of pain or inflammation of a tendon (e.g., in the ankle, wrist, elbow, shoulder, or knee), stop taking levofloxacin, contact your doctor, and rest the affected area. Avoid any unnecessary exercise, as this could increase the risk of tendon rupture.

Rarely, you may experience symptoms of nerve damage (neuropathy) such as pain, burning, tingling, numbness, and/or weakness, especially in the feet and legs or hands and arms. If this happens, stop taking levofloxacin and inform your doctor immediately to prevent the development of a potentially irreversible disorder.

Severe, Long-Lasting, and Potentially Irreversible Side Effects

Antibacterial medicines that contain fluoroquinolones or quinolones, including levofloxacin, have been associated with very rare but serious side effects, some of which were long-lasting (persisting for months or years), disabling, or potentially irreversible. These include pain in the tendons, muscles, and joints of the upper and lower limbs, difficulty walking, abnormal sensations such as pins and needles, tingling, prickling, numbness, or burning (paresthesia), sensory disorders such as decreased vision, taste, smell, and hearing, depression, decreased memory, intense fatigue, and severe sleep disorders.

If you experience any of these side effects after taking levofloxacin, contact your doctor immediately before continuing treatment. You and your doctor will decide whether to continue or not, also considering the use of an antibiotic of another class.

If you are unsure whether any of the above cases apply to you, inform your doctor, pharmacist, or nurse before they administer this medicine to you.

Other Medicines and Levofloxacino Aurovitas Solution for Infusion

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is because levofloxacin may affect the way some medicines work, and some of these may affect the way levofloxacin works.

In particular, inform your doctor if you are taking any of the following medicines, as this increases the likelihood of experiencing side effects when taking them with levofloxacin solution for infusion:

• Corticosteroids, sometimes called steroids - used for inflammation. You may be more likely to experience tendon inflammation and/or rupture.
• Warfarin - used to make the blood more fluid. You may be more likely to experience bleeding. Your doctor may need to perform periodic blood tests to check if your blood is clotting correctly.
• Theophylline - used for respiratory problems. You may be more likely to experience a seizure (convulsions) if you take it with levofloxacin.
• Non-steroidal anti-inflammatory drugs (NSAIDs) - used for pain and inflammation, such as acetylsalicylic acid, ibuprofen, fenbufen, ketoprofen, and indomethacin. You may be more likely to experience a seizure (convulsions) when taking them with levofloxacin.
• Cyclosporine - used after organ transplants. You may be more likely to experience the side effects of cyclosporine.
• Medicines that affect your heart rhythm. This includes medicines used for abnormal heart rhythm (antiarrhythmics such as quinidine, hydroquinidine, disopyramide, sotalol, dofetilide, ibutilide, and amiodarone), for depression (tricyclic antidepressants such as amitriptyline and imipramine), for psychiatric disorders (antipsychotics), and for bacterial infections (macrolide antibiotics such as erythromycin, azithromycin, and clarithromycin).
• Probenecid (used for gout). Your doctor may need to give you a lower dose if you have kidney problems.
• Cimetidine (used for ulcers and heartburn). Your doctor may need to give you a lower dose if you have kidney problems.

Tell your doctor if any of the above cases apply to you.

Opiate Determination in Urine

Urine tests may show "false positive" results for the presence of strong painkillers called "opioids" in patients using levofloxacin. Inform your doctor that you are using levofloxacin if you have been prescribed a urine test.

Tuberculosis Test

This medicine may cause a "false negative" result in some laboratory tests used to detect the bacteria that cause tuberculosis.

Pregnancy and Breastfeeding

Do not use this medicine if:

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

Driving and Using Machines

Some side effects may occur, including dizziness, drowsiness, balance disturbance (vertigo), or visual disturbances. Some of these side effects may affect your ability to concentrate or reduce your reaction time. If this happens, do not drive or perform any work that requires a high level of attention.

Levofloxacino Aurovitas Solution for Infusion Contains Sodium

Patients on low-sodium diets should note that this medicine contains 177 mg (7.7 mmol) of sodium per 50 ml dose and 354 mg (15.4 mmol) of sodium per 100 ml dose.

3. How to use Levofloxacino Aurovitas solution for infusion

How to use Levofloxacino Aurovitas solution for infusion

• Levofloxacino solution for infusion is a medication for use in hospitals.
• It will be administered to you by a doctor or nurse via an injection. The injection will be administered into one of your veins and over a period of time (this is called intravenous infusion).
• For 250 mg of levofloxacino solution for infusion, the infusion time will be 30 minutes or more.
• For 500 mg of levofloxacino solution for infusion, the infusion time will be 60 minutes or more.
• Your heart rate and blood pressure will be frequently monitored. This is because an abnormal fast heartbeat and a temporary decrease in blood pressure are possible adverse effects that have been seen during the infusion of a similar antibiotic. If your blood pressure drops significantly while you are being administered the infusion, it will be interrupted immediately.

How much Levofloxacino Aurovitas solution for infusion is administered

If you are not sure why you are being administered levofloxacino or have any questions about how much levofloxacino you are being administered, consult your doctor, nurse, or pharmacist.

• Your doctor will decide how much levofloxacino you should be administered.
• The dose will depend on the type of infection you have and where it is located in your body.
• The duration of treatment will depend on the severity of your infection.

Adults and elderly patients

• Pneumonia: 500 mg once or twice a day.
• Urinary tract infection, including kidneys or bladder: 500 mg once a day.
• Prostate infection: 500 mg once a day.
• Skin and soft tissue infection, including muscles: 500 mg once or twice a day.

Adults and elderly patients with kidney problems

Your doctor may administer a lower dose to you.

Children and adolescents

This medication should not be administered to children or adolescents.

Protect your skin from sunlight

Do not expose your skin directly to the sun (even on cloudy days) while you are being administered this medication and for two days after stopping use, as your skin will become much more sensitive to the sun and may burn, sting, or even blister if you do not take the following precautions:

• Make sure to use high-protection sun creams.
• Always wear a hat and clothing that covers your arms and legs.
• Avoid UVA lamps.

If you use more Levofloxacino Aurovitas solution for infusion than you should

It is unlikely that your doctor or nurse will administer more medication than you need. Your doctor and nurse will monitor your progress and control the medication that has been administered to you. Always ask if you are not sure why you are being administered this medication.

If you are administered more levofloxacino than you need, the following effects may appear: epileptic seizures (convulsions), confusion, dizziness, decreased consciousness, tremors, heart disorders that can cause irregular heartbeats, as well as discomfort (nausea).

If you forget to use Levofloxacino Aurovitas solution for infusion

Your doctor or nurse will have instructions on when to give you this medication. It is unlikely that you will not be administered the medication as prescribed. However, if you think you have forgotten a dose, inform your doctor or nurse.

If you interrupt treatment with Levofloxacino Aurovitas solution for infusion

Your doctor or nurse will continue to administer levofloxacino to you, even if you feel better. If treatment is interrupted too early, the infection may recur, you may worsen, or the bacteria may become resistant to the medication. After a few days of treatment with the solution for infusion, your doctor may decide to switch you to the tablet form of this medication to complete the treatment.

If you have any other questions about the use of this medication, ask your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them. They are usually mild to moderate and tend to disappear in a short time.

Stop treatment with levofloxacino and contact a doctor or nurse immediately if you notice the following side effects:

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

• If you have an allergic reaction. The signs may include: skin rash, difficulty swallowing or breathing, swelling of lips, face, throat, or tongue.

Stop treatment with levofloxacino and contact a doctor or nurse immediately if you notice any of the following serious side effects, as you may need urgent medical treatment:

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

• Widespread rash, high body temperature, elevated liver enzymes, blood abnormalities (eosinophilia), swollen lymph nodes, and other body organs involved (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome). See also section 2.
• Syndrome associated with alterations in water elimination and low sodium levels (SIADH).
• Watery diarrhea that may contain blood, possibly with stomach cramps and fever. These could be signs of a serious intestinal problem.
• Pain and inflammation in the tendons or ligaments, which could lead to rupture. The Achilles tendon is the most commonly affected.
• Epileptic seizures (convulsions).
• Seeing or hearing things that are not real (hallucinations, paranoia).
• Depression, mental disorders, feeling of restlessness (agitation), abnormal dreams, or nightmares.
• Decreased blood sugar levels (hypoglycemia) or decreased blood sugar levels that can lead to coma (hypoglycemic coma). This is important for diabetic patients.

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

• Burning, tingling, pain, or numbness. These can be signs of what is called "neuropathy".

Frequency not known(cannot be estimated from available data)

• Severe skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear on the torso as reddish patches in a target shape or circular spots often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by flu-like symptoms. See also section 2.
• Loss of appetite, yellowing of skin and eyes, dark urine, itching, or painful stomach. These can be signs of liver problems that can include fulminant liver failure.
• Changes in opinion and thoughts (psychotic reactions) with a risk of having suicidal thoughts or actions.
• Nausea, general discomfort, stomach upset, or vomiting. These could be signs of an inflamed pancreas (acute pancreatitis). See section 2.

Consult an eye specialist immediately if your vision deteriorates or you have any other eye problems while being treated with levofloxacino.

The administration of antibiotics containing quinolones and fluoroquinolones has been associated with very rare cases of long-lasting (even months or years) or permanent adverse reactions, such as tendon inflammation, tendon rupture, joint pain, limb pain, difficulty walking, abnormal sensations such as pinching, tingling, burning, numbness, or pain (neuropathy), depression, fatigue, sleep disorders, memory loss, and loss of hearing, vision, taste, and smell, in some cases regardless of the presence of pre-existing risk factors.

There have been reports of increased size and weakening or tearing of the aortic wall (aneurysms and dissections), which can lead to rupture and be fatal, and cardiac valve insufficiency in patients who have received fluoroquinolones. See also section 2.

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

Common(may affect up to 1 in 10 people)

• Sleep problems.
• Headache, dizziness.
• Discomfort (nausea, vomiting) and diarrhea.
• Increased levels of some liver enzymes in the blood.
• Reactions at the infusion site.
• Vein inflammation.

Uncommon(may affect up to 1 in 100 people)

• Changes in the number of other bacteria or fungi, infection by a fungus called Candida, which may require treatment.
• Changes in the number of white blood cells in your blood test results (leukopenia, eosinophilia).
• Stress (anxiety), confusion, nervousness, drowsiness, tremors, feeling of dizziness (vertigo).
• Difficulty breathing (dyspnea).
• Changes in taste, loss of appetite, stomach upset, or indigestion (dyspepsia), stomach pain, feeling of bloating (flatulence), or constipation.
• Itching and skin rash, intense itching, or hives (urticaria), excessive sweating (hyperhidrosis).
• Joint or muscle pain.
• Abnormal blood test results due to liver (increased bilirubin) or kidney (increased creatinine) problems.
• Generalized weakness.

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

• Appearance of bruises and easy bleeding due to a decrease in the number of platelets in the blood (thrombocytopenia).
• Decrease in the number of white blood cells in the blood (neutropenia).
• Exaggerated immune response (hypersensitivity).
• Feeling of tingling in hands and feet (paresthesias).
• Ear disorders (tinnitus) or vision problems (blurred vision).
• Abnormally fast heartbeat (tachycardia) or decreased blood pressure (hypotension).
• Muscle weakness. This is important in people with myasthenia gravis (a rare nervous system disease).
• Changes in kidney function and, sometimes, kidney failure, which can be a consequence of an allergic reaction in the kidney called interstitial nephritis.
• Fever.
• Red, clearly defined patches with or without blisters, which develop a few hours after the administration of levofloxacino and heal with residual post-inflammatory hyperpigmentation; usually, they recur in the same area of the skin or mucous membrane after subsequent exposure to levofloxacino.
• Memory loss.

Frequency not known(cannot be estimated from available data)

• Decrease in red blood cells (anemia): this can cause the skin to become pale or yellow due to damage to red blood cells; decrease in the number of all types of blood cells (pancytopenia).
• Fever, sore throat, and persistent general discomfort. This can be due to a decrease in the number of white blood cells (agranulocytosis).
• Circulatory collapse (anaphylactic shock).
• Increased blood sugar levels (hyperglycemia). This is important in people with diabetes.
• Changes in smell, loss of smell or taste (parosmia, anosmia, ageusia).
• Movement and gait disorders (dyskinesia, extrapyramidal disorders).
• Temporary loss of consciousness or posture (syncope).
• Temporary loss of vision, eye inflammation.
• Hearing problems or hearing loss.
• Abnormally fast heartbeat, life-threatening irregular heartbeat, including cardiac arrest, alteration of heart rhythm (called "prolongation of the QT interval", observed in the ECG, a graphical representation of the heart's electrical activity).
• Difficulty breathing or wheezing (bronchospasm).
• Pulmonary allergic reactions.
• Pancreas inflammation (pancreatitis).
• Liver inflammation (hepatitis).
• Increased skin sensitivity to sunlight and ultraviolet light (photosensitivity).
• Inflammation of the blood vessels that carry blood throughout the body due to an allergic reaction (vasculitis).
• Inflammation of the tissue inside the mouth (stomatitis).
• Muscle rupture and destruction (rhabdomyolysis).
• Red and swollen joints (arthritis).
• Pain, including back, chest, and limb pain.
• Porphyria crisis in patients with porphyria (a very rare metabolic disease).
• Persistent headache with or without blurred vision (benign intracranial hypertension).
• Loss of consciousness due to a severe decrease in blood sugar levels (hypoglycemic coma). See section 2.

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Conservation of Levofloxacino Aurovitas solution for infusion

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box and vial after CAD. The expiration date is the last day of the month indicated.

Keep the vial in the outer packaging to protect it from light. During infusion, no light protection is required.

Once the vial is opened for infusion (puncture of the rubber stopper), the solution must be used immediately (within 3 hours) to prevent microbiological contamination.

Do not use this medication if you observe that the solution is not transparent, has a yellowish-green color, and/or has particles.

Medications should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Levofloxacino Aurovitas Solution for Infusion

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

Each 50 ml vial of solution for infusion contains 250 mg of levofloxacino (as hemihydrate).

Each 100 ml vial of solution for infusion contains 500 mg of levofloxacino (as hemihydrate).

• The other components are: sodium chloride, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Product Appearance and Container Content

Levofloxacino Aurovitas solution for infusion is a clear yellowish-green solution, particle-free, with a pH of 4.2 to 5.5.

50 ml glass vial type I, transparent, with a gray bromobutyl rubber stopper and an aluminum cap with a polypropylene disc. Each vial contains 50 ml of solution.

100 ml glass vial type I, transparent, with a gray bromobutyl rubber stopper and an aluminum cap with a polypropylene disc. Each vial contains 100 ml of solution.

Package sizes:

50 ml: 1, 5, and 10 vials.

100 ml: 1, 5, 10, and 20 vials.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of this leaflet: December 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended only for healthcare professionals:

For single use. Levofloxacino solution for infusion should be used immediately (within 3 hours) after the rubber stopper is pierced to prevent microbial contamination. Keep the vial in the outer packaging to protect it from light. During infusion, no protection from light is required.

The solution should be inspected visually before use. It should only be used if the solution is clear, yellowish-green in color, and particle-free.

Administration Method

Levofloxacino Aurovitas solution for infusion is only indicated for slow intravenous infusion; it is administered once or twice a day. The infusion time should be at least 30 minutes for 250 mg of levofloxacino solution for infusion or 60 minutes for 500 mg of levofloxacino solution for infusion. During the infusion time, the patient should be examined for any signs of severe tachycardia (rapid heartbeat) and a transient decrease in blood pressure. In rare cases, circulatory problems may occur as a result of a significant drop in blood pressure.

Mixing with Other Infusion Solutions

Levofloxacino Aurovitas 5 mg/ml solution for infusion is physically compatible and chemically stable at controlled room temperature (i.e., 15-25°C) for up to 8 hours when mixed with the following infusion solutions in the concentration range of 0.5 mg/ml to 2 mg/ml.

• Sodium chloride 0.9% solution.
• 5% injectable glucose.
• 2.5% glucose in Ringer's solution.
• Parenteral nutrition combination solutions (amino acids, glucose, electrolytes).

Incompatibilities

This medicinal product should not be mixed with:

• Heparin.
• Alkaline solutions (e.g., sodium bicarbonate).