PIPERACILLIN/TAZOBACTAM AUROVITAS 2 g/0.25 g POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you use Piperacillin/Tazobactam Aurovitas

Do not use Piperacillin/Tazobactam Aurovitas

• if you are allergic to piperacillin, tazobactam, or any of the other components of this medicine (listed in section 6).
• if you are allergic to antibiotics called penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may be allergic to piperacillin/tazobactam.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Piperacillin/Tazobactam Aurovitas:

• if you have allergies. If you have multiple allergies, make sure to tell your doctor or other healthcare professional before receiving this medicine.
• if you had diarrhea before treatment or if you start to have it during or after treatment. In this case, make sure to tell your doctor or other healthcare professional immediately. Do not take any medicine for diarrhea without consulting your doctor first.
• if you have low potassium levels in your blood. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment.
• if you have kidney or liver problems or are undergoing hemodialysis. Your doctor may want to check your kidneys before you receive this medicine and may perform periodic blood tests during treatment.
• if you are using another antibiotic called vancomycin at the same time as piperacillin/tazobactam, it may increase the risk of kidney damage (see also Other medicines and Piperacillin/Tazobactam Aurovitas in this leaflet).
• if you are using certain medicines (called anticoagulants) to prevent excessive blood clotting (see also Other medicines and Piperacillin/Tazobactam Aurovitas in this leaflet) or if you experience unexpected bleeding during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• if you experience seizures during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• if you think you have developed a new infection or your infection has worsened. In this case, you must inform your doctor or other healthcare professional immediately.

Hemophagocytic lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many white blood cells, otherwise normal, called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This disease can be potentially fatal if not diagnosed and treated early. If you experience multiple symptoms such as fever, swelling of the lymph nodes, feeling of weakness, feeling of dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

Children under 2 years

Piperacillin/tazobactam is not recommended for use in children under 2 years due to the lack of data on safety and efficacy.

Other medicines and Piperacillin/Tazobactam Aurovitas

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

Some medicines may interact with piperacillin or tazobactam. These include:

• a medicine for gout (probenecid). This medicine may increase the time it takes for piperacillin and tazobactam to be eliminated from the body.
• medicines used to thin the blood or treat blood clots (e.g., heparin, warfarin, or acetylsalicylic acid).
• medicines used to relax muscles during surgery. Inform your doctor if you are going to undergo general anesthesia.
• methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time it takes for methotrexate to be eliminated from the body.
• medicines that decrease potassium levels in the blood (e.g., diuretic pills or certain cancer medicines).
• medicines that contain other antibiotics such as tobramycin, gentamicin, or vancomycin.
• Tell your doctor if you have kidney problems. The use of piperacillin/tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if you do not have kidney problems.

Effects on laboratory tests

If you need to provide a blood or urine sample, tell your doctor or laboratory staff that you are using piperacillin/tazobactam.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will decide if piperacillin/tazobactam is suitable for you.

Piperacillin and tazobactam may pass to the fetus in the womb or through breast milk. If you are breastfeeding, your doctor will decide if piperacillin/tazobactam is suitable for you.

Driving and using machines

It is not expected that the use of piperacillin/tazobactam will affect your ability to drive or use machines.

Piperacillin/Tazobactam Aurovitas contains sodium

This medicine contains 108 mg of sodium (main component of cooking/table salt) in each vial. This is equivalent to 5.4% of the maximum recommended daily intake of sodium for an adult. This should be taken into account in patients on a low-sodium diet.

3. How to use Piperacillin/Tazobactam Aurovitas

Your doctor or other healthcare professional will administer this medicine to you by intravenous infusion (into a vein with a drip over 30 minutes).

Dosage

The dose of medicine that you will be given depends on what you are being treated for, your age, and whether you have kidney problems or not.

Adults and adolescents 12 years and older

The normal dose is 4 g/0.5 g of piperacillin/tazobactam administered every 6-8 hours through a vein (directly into the bloodstream).

Children 2 to 12 years old

The normal dose for children with abdominal infections is 100 mg/12.5 mg/kg of body weight of piperacillin/tazobactam administered every 8 hours through a vein (directly into the bloodstream). The usual dose for children with low white blood cell counts is 80 mg/10 mg/kg of body weight of piperacillin/tazobactam administered every 6 hours through a vein (directly into the bloodstream).

Your doctor will calculate the dose based on the child's weight, but each individual dose will not exceed 4 g/0.5 g of piperacillin/tazobactam.

You will be given piperacillin/tazobactam until the signs of infection have completely disappeared (from 5 to 14 days).

Patients with kidney problems

It may be necessary for your doctor to reduce the dose of piperacillin/tazobactam or the frequency of administration. Your doctor may also want to perform blood tests to ensure you are receiving the correct dose of treatment, especially if you need to use this medicine for a long time.

If you use more Piperacillin/Tazobactam Aurovitas than you should

Because a doctor or other healthcare professional will administer piperacillin/tazobactam to you, it is unlikely that you will receive an incorrect dose. However, if you experience side effects such as seizures or think you have been given too much medicine, tell your doctor immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount administered.

If you miss a dose of Piperacillin/Tazobactam Aurovitas

If you think you have missed a dose of piperacillin/tazobactam, tell your doctor or other healthcare professional immediately.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Consult your doctor immediatelyif you experience any of these potentially serious side effects of piperacillin/tazobactam.

The serious side effects (with frequency in parentheses) of piperacillin/tazobactam are:

• severe skin rashes [(Stevens-Johnson syndrome, bullous dermatitis (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)] that initially appear on the trunk as red spots with a target-like shape or circular spots with central blisters. Other signs include ulcers in the mouth, throat, nose, limbs, genitals, and conjunctivitis (red and swollen eyes). The rash can progress to blistering or peeling of the skin and potentially be fatal.
• severe allergic reaction potentially leading to death (drug reaction with eosinophilia and systemic symptoms) that can affect the skin and other vital organs such as the kidneys and liver.
• a skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small pus-filled spots that appear on large areas of swollen and red skin.
• swelling of the face, lips, tongue, or other parts of the body (frequency not known).
• shortness of breath, wheezing, or difficulty breathing (frequency not known).
• severe skin rash or hives on the skin (uncommon), itching or rash on the skin (common).
• yellowing of the eyes and skin (frequency not known).
• damage to blood cells [symptoms include: shortness of breath when not expected, urine of red or brown color (frequency not known), nosebleeds (rare), small bruises (frequency not known), severe decrease in white blood cells in the blood (rare)].
• severe or persistent diarrhea accompanied by fever or weakness (rare).

If any of the followingside effects is severe or if you experience any side effect not mentioned in this leaflet, inform your doctor or other healthcare professional.

Very common side effects(may affect more than 1 in 10 people)

• diarrhea.

Common side effects(may affect up to 1 in 10 people)

• yeast infection.
• decrease in platelets, decrease in red blood cells or hemoglobin (blood pigment), abnormal laboratory tests (direct Coombs test positive), prolonged blood clotting time (prolonged activated partial thromboplastin time).
• decrease in blood proteins.
• headache, insomnia.
• abdominal pain, vomiting, nausea, constipation, stomach upset.
• increase in liver enzymes in the blood.
• skin rashes, itching.
• abnormal kidney blood tests.
• fever, reaction at the injection site.

Uncommon side effects(may affect up to 1 in 100 people)

• decrease in white blood cells in the blood (leukopenia), prolonged blood clotting time (prolonged prothrombin time).
• decrease in potassium levels in the blood, decrease in blood sugar levels.
• seizures (convulsions), observed in patients receiving high doses or with kidney problems.
• low blood pressure, inflammation of the veins (pain when touching or redness of the affected area), redness of the skin.
• increase in a breakdown product of the blood pigment (bilirubin).
• skin reactions with redness, formation of skin lesions, hives.
• muscle and joint pain.
• chills.

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

• severe decrease in white blood cells (agranulocytosis), nosebleeds.
• severe colon infection, inflammation of the mucous membrane of the mouth.
• peeling of the top layer of the skin all over the body (toxic epidermal necrolysis).

Side effects with frequency not known(cannot be estimated from the available data)

• severe decrease in red blood cells, white blood cells, and platelets (pancytopenia), decrease in white blood cells (neutropenia), decrease in red blood cells due to premature rupture or breakdown, small bruises, prolonged bleeding time, increase in platelets, increase in a specific type of white blood cells (eosinophilia).
• allergic reaction and severe allergic reaction.
• inflammation of the liver, yellowing of the skin or the whites of the eyes.
• severe allergic reaction all over the body with skin and mucous membrane rashes, blisters, and various skin rashes (Stevens-Johnson syndrome), severe allergic reactions that affect the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small pus-filled spots that appear on large areas of swollen and red skin accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis).
• kidney function impairment and kidney problems.
• a type of lung disease where eosinophils (a type of white blood cell) appear in the lungs in greater numbers.
• acute confusion and disorientation (delirium).

In patients with cystic fibrosis, treatment with piperacillin has been associated with an increased incidence of fever and skin rashes.

Beta-lactam antibiotics, including piperacillin/tazobactam, may cause signs of brain function alteration (encephalopathy) and seizures.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects 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 medicine.

5. Storage of Piperacillin/Tazobactam Aurovitas

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month stated.

Powder:

Unopened vials: Store below 25°C.

For single use. Discard unused solution.

The reconstituted/diluted solutions of the medicinal product are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and 48 hours at 2-8°C.

From a microbiological point of view, the reconstituted and diluted solutions should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the reconstitution and dilution have taken place in controlled and validated aseptic conditions.

Medicines should not be disposed of 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 Additional Information

Composition of Piperacillin/Tazobactam Aurovitas

• The active substances are piperacillin and tazobactam. Each vial contains 2 g of piperacillin (as sodium salt) and 0.25 g of tazobactam (as sodium salt).
• There are no other ingredients.

Appearance and Package Contents of the Product

White to off-white powder for solution for infusion.

Piperacillin/Tazobactam Aurovitas is available in packs of 1, 10 or 12 vials packaged in cardboard boxes with a leaflet.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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 Authorisation Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Date of Last Revision of this Leaflet:December 2022

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 solely for healthcare professionals:

Note: Use is not recommended for bacteremia due to E. coliand K. pneumoniae(non-susceptible to ceftriaxone) producing extended-spectrum beta-lactamase (ESBL) in adult patients.

Piperacillin/Tazobactam Aurovitas 2 g/0.25 g powder for solution for infusion EFG

The following text is an excerpt from the Summary of Product Characteristics that serves as a guide for the administration of Piperacillin/Tazobactam Aurovitas. When determining the suitability of use in a particular patient, the prescribing physician should be familiar with the Summary of Product Characteristics.

For slow intravenous infusion.

Incompatibilities with Diluents and Other Medicinal Products

• Ringer's Lactate (Hartmann) solution is not compatible with piperacillin/tazobactam.
• When used concomitantly with other antibiotics (e.g., aminoglycosides), piperacillin/tazobactam should be administered separately. Mixing piperacillin/tazobactam with an aminoglycoside in vitro may cause inactivation of the aminoglycoside.
• Piperacillin/tazobactam should not be mixed with other medicinal products in a syringe or infusion bottle, as compatibility has not been established.
• Due to chemical instability, piperacillin/tazobactam should not be used in solutions containing sodium bicarbonate.
• Piperacillin/tazobactam should not be added to blood products or albumin hydrolysates.

Instructions for Use, Handling, and Disposal

Reconstitution and dilution should be carried out under aseptic conditions. Before administration, the solution should be visually inspected for particles and color change. The solution should only be used if it is clear and free of particles.

Instructions for inserting the needle into the rubber stopper

To avoid the rubber stopper being dislodged when inserting the needle into the rubber stopper, it is recommended to use a needle with an outer diameter of 0.8 mm or less for reconstitution of the medicinal product.

The needle should be inserted only into the center of the rubber stopper, in a vertical direction.

For single use. Discard unused solution.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Sterile diluents for preparing the reconstituted solution

• Sterile water for injections.
• Sodium chloride 9 mg/ml (0.9%) injection solution.
• Glucose 50 mg/ml (5%) in water for injections.
• Glucose 50 mg/ml (5%) in sodium chloride 9 mg/ml (0.9%) injection solution.

Instructions for dilution (for intravenous infusion)

Each vial of piperacillin/tazobactam 2 g/0.25 g should be reconstituted with 10 ml of the above diluents.

Shake until completely dissolved.

The reconstituted solutions can be further diluted to a concentration range of 13.33/1.67 mg/ml to 80/10 mg/ml with the following diluents:

• Sterile water for injections.
• Sodium chloride 9 mg/ml (0.9%) injection solution.
• Glucose 50 mg/ml (5%) in water for injections.
• Glucose 5% in sodium chloride 0.9% solution.

Special Precautions for Storage

Unopened vials: Store below 25°C.

The reconstituted/diluted solutions of the medicinal product are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and 48 hours at 2-8°C.

From a microbiological point of view, the reconstituted and diluted solutions should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the reconstitution and dilution have taken place in controlled and validated aseptic conditions.