PIPERACILLIN/TAZOBACTAM SANDOZ 4 g/0.5 g POWDER FOR SOLUTION FOR INFUSION

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

Do not use Piperacillin/Tazobactam Sandoz

• if you are allergic to piperacillin or tazobactam or any of the other ingredients 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 or pharmacist or nurse before starting to use piperacillin/tazobactam:

• if you have allergies. If you have multiple allergies, make sure to tell your doctor or other healthcare professional before receiving this product,
• if you have 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 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 Sandoz in this leaflet),
• if you have kidney or liver problems, or if you are undergoing hemodialysis. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment,
• if you are using certain medicines (called anticoagulants) to prevent excessive blood clotting (see also “Other medicines and Piperacillin/Tazobactam Sandoz” 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 if 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 of age due to the lack of safety and efficacy data.

Other medicines and Piperacillin/Tazobactam Sandoz

Tell your doctor or other healthcare professional 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 product may increase the time it takes for piperacillin and tazobactam to be eliminated from the body,
• medicines used to thin the blood or to 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. Inform 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 and breastfeeding

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

Piperacillin and tazobactam may pass to the baby in the womb or through breast milk. If you are breastfeeding a baby, 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 Sandoz will affect your ability to drive or use machines.

Piperacillin/Tazobactam Sandoz 2g/0.25g contains sodium

This medicine contains 109 mg of sodium (main component of table/cooking salt) per vial. This is equivalent to 6% of the maximum recommended daily sodium intake for an adult.

Piperacillin/Tazobactam Sandoz 4g/0.5g contains sodium

This medicine contains 217 mg of sodium (main component of table/cooking salt) per vial. This is equivalent to 11% of the maximum recommended daily sodium intake for an adult.

This should be taken into account in patients with low-sodium diets.

3. How to use Piperacillin/Tazobactam Sandoz

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

Dose

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

Adults and adolescents over 12 years of age

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

Children from 2 to 12 years of age

The usual 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. It is also possible that your doctor may want to perform blood tests to ensure that 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 Sandoz than you should

Since a doctor or other healthcare professional will be administering 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 that you have been given too much medicine, tell your doctor immediately.

If you have taken more piperacillin/tazobactam than you should, consult your doctor, pharmacist, or nurse immediately. You can also contact the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you forget to use Piperacillin/Tazobactam Sandoz

If you think that you have not been given a dose of piperacillin/tazobactam, tell your doctor or other healthcare professional immediately.

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

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 (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] that initially appear as reddish spots or circular patches with central blisters on the torso. 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 can be potentially fatal,
• potentially serious allergic reaction (drug reaction with eosinophilia and systemic symptoms) that can affect the skin and other major organs of the body such as the kidneys and liver (not known),
• a skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small fluid-filled blisters that appear on large areas of swollen and reddened skin (not known),

• swelling of the face, lips, tongue, or other parts of the body (not known),
• shortness of breath, wheezing, or difficulty breathing (not known),
• severe or widespread rash or hives (uncommon), itching or rash on the skin (not known),
• yellowing of the eyes and skin (not known),
• damage to blood cells (symptoms include: shortness of breath when not expected, urine of red or brown color (not known), nosebleeds (rare), bruising (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, tell 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 destruction, 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 affecting the whole body with skin and mucous membrane rashes, blisters, and various skin rashes (Stevens-Johnson syndrome), severe allergic reactions affecting the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters that appear on large areas of swollen and reddened 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 disorientation and confusion (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 impairment (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 side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Piperacillin/Tazobactam Sandoz

Keep out of the sight and reach of children.

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

Vials/bottles not opened:

No special storage conditions are required.

For the storage conditions of the medicine once reconstituted and diluted, see the end of the leaflet "This information is intended only for healthcare professionals”.

For single use only. Discard unused solution.

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. Container Content and Additional Information

Composition of Piperacillin/Tazobactam Sandoz

• The active ingredients are piperacillin and tazobactam.

Piperacillin/Tazobactam Sandoz 2 g/0.25 g

Each vial contains 2 g of piperacillin (as piperacillin sodium) and 0.25 g of tazobactam (as tazobactam sodium).

Piperacillin/Tazobactam Sandoz 4 g/0.5 g

Each vial contains 4 g of piperacillin (as piperacillin sodium) and 0.5 g of tazobactam (as tazobactam sodium).

• The other components are:

This medication does not contain any other ingredients besides the active ingredients.

Appearance of the Product and Container Content

Piperacillin/Tazobactam Sandoz 2 g/0.25 g is a white or off-white powder for solution for infusion, supplied in glass vials.

The vials are packaged in cardboard boxes.

Container sizes: 1, 5, 10, 12, and 50 vials.

Piperacillin/Tazobactam Sandoz 4 g/0.5 g is a white or off-white powder for solution for infusion, supplied in glass vials or bottles.

The vials or bottles are packaged in cardboard boxes.

Container sizes: 1, 5, 10, 12, and 50 vials or bottles.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer:

Sandoz GmbH

Biochemiestrasse 10

A-6250 Kundl

Austria

This medication is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Slovakia: Piperacillin comp. Sandoz 4 g/0.5 g powder for infusion solution

France: PIPERACILLINE/TAZOBACTAM SANDOZ 4 g/0.5 g, powder for solution for infusion

Hungary: Piperacillin/Tazobactam Sandoz 4 g/0.5 g powder for infusion solution

Ireland: Piperin 2 g/0.25 g Powder for Solution for Infusion

Piperin 4 g/0.5 g Powder for Solution for Infusion

Netherlands: Piperacilline/Tazobactam Sandoz 2 g/0.25 g powder for infusion solution

Piperacilline/Tazobactam Sandoz 4 g/0.5 g powder for infusion solution

Sweden: Piperazillin/Tazobactam Sandoz 2 g/0.25 g powder for injection/infusion solution

Piperazillin/Tazobactam Sandoz 4 g/0.5 g powder for injection/infusion solution

Spain: Piperacilina/Tazobactam Sandoz 2 g/0.25 g powder for solution for infusion EFG

Piperacilina/Tazobactam Sandoz 4 g/0.5 g powder for solution for infusion EFG

Date of the Last Revision of this Leaflet:January 2023.

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

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This information is intended only for healthcare professionals:

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

After Reconstitution (and Dilution)

Physical and chemical stability has been demonstrated for 24 hours at a temperature of 20-25°C and for 48 hours at 2-8°C.

From a microbiological point of view, once opened, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not exceed 24 hours at a temperature of 2-8°C, unless the reconstitution/dilution takes place in validated and controlled aseptic conditions.

Instructions for Use

Piperacillin/Tazobactam should be administered by intravenous infusion (drip over 30 minutes).

Reconstitution and dilution should be performed in aseptic conditions. Before administration, the solution should be visually inspected for particles and color change. The solution should only be used if it is transparent and free of particles.

Intravenous Route

Each vial/bottle should be reconstituted with the volume of solvent shown in the following table, using one of the compatible solvents for reconstitution. Shake with rotary movements until dissolved. If shaken constantly, it is usually reconstituted within 3 minutes (see handling details below).

• Compatible solvents for reconstitution:
  • sterile water for injection,
  • 9 mg/ml sodium chloride (0.9%) solution in water for injection,
  • 50 mg/ml glucose (5%) solution in water for injection,
  • 50 mg/ml glucose (5%) solution in 9 mg/ml sodium chloride (0.9%) solution.

The reconstituted solutions should be withdrawn from the vial with a syringe. After reconstitution as indicated, the content of the vial withdrawn with a syringe will provide the nominal amount of piperacillin and tazobactam.

The reconstituted solutions can be further diluted to the desired volume (i.e., 50 ml to 150 ml) with one of the following compatible solvents:

• 9 mg/ml sodium chloride (0.9%) solution in water for injection,
• 50 mg/ml glucose (5%) solution in water for injection,
• dextran (grade 40) 60 mg/ml (6%) in 9 mg/ml sodium chloride (0.9%) solution.

Incompatibilities

Whenever Piperacillin/Tazobactam is used simultaneously with another antibiotic (e.g., aminoglycosides), they should be administered separately. The mixture of beta-lactam antibiotics with aminoglycosides in vitrocan result in substantial inactivation of the aminoglycoside. However, it has been determined that amikacin and gentamicin are compatible with piperacillin/tazobactam in vitrowith certain diluents at specific concentrations (see Co-administration with Aminoglycosidesbelow).

Piperacillin/Tazobactam Sandoz should not be mixed with other substances in a syringe or infusion bottle, as its compatibility has not been established.

Piperacillin/Tazobactam should be administered through a separate infusion set from any other medication, unless compatibility has been demonstrated.

Due to chemical instability, Piperacillin/Tazobactam Sandoz should not be used with solutions containing only sodium bicarbonate.

Piperacillin/Tazobactam Sandoz is not compatible with Ringer's Lactate (Hartmann) solution.

Piperacillin/Tazobactam Sandoz should not be added to hemoderivatives or albumin hydrolysates.

Co-administration of Piperacillin/Tazobactam with Aminoglycosides

Due to the in vitroinactivation of the aminoglycoside by beta-lactam antibiotics, it is recommended to administer piperacillin/tazobactam and the aminoglycoside separately.

Piperacillin/tazobactam and the aminoglycoside should be reconstituted and diluted separately when concomitant treatment with aminoglycosides is indicated.

In circumstances where co-administration is recommended, piperacillin/tazobactam is compatible for simultaneous co-administration by Y-infusion only with the following aminoglycosides under the following conditions:

• The aminoglycoside dose should be based on the patient's weight, infection status (severe or life-threatening), and renal function (creatinine clearance).

The compatibility of piperacillin/tazobactam with other aminoglycosides has not been established. Only the concentrations and diluents for amikacin and gentamicin with the piperacillin/tazobactam doses indicated in the table above have been established as compatible for co-administration by Y-infusion.

Simultaneous administration by Y-infusion in any other manner than that indicated above may result in the inactivation of the aminoglycoside by piperacillin/tazobactam.