Piperacillin/tazobactam Noridem

PATIENT INFORMATION LEAFLET

Information leaflet included in the packaging: information for the user

Piperacillin/Tazobactam Noridem, 2g + 0.25g, powder for solution for infusion

Piperacillin/Tazobactam Noridem, 4g + 0.5g, powder for solution for infusion

piperacillin + tazobactam

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 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, pharmacist, or nurse. See section 4.

The medicine is known by one of the following names:

• Piperacillin/Tazobactam Noridem, 2g + 0.25g, Powder for solution for infusion
• Piperacillin/Tazobactam Noridem, 4g + 0.5g, Powder for solution for infusion In the rest of this leaflet, the medicine will be called Piperacillin/Tazobactam.

Table of contents of the leaflet

• 1. What is Piperacillin/Tazobactam and what is it used for
• 2. Important information before using Piperacillin/Tazobactam
• 3. How to use Piperacillin/Tazobactam
• 4. Possible side effects
• 5. How to store Piperacillin/Tazobactam
• 6. Contents of the pack and other information

1. What is Piperacillin/Tazobactam and what is it used for

Piperacillin belongs to a group of medicines called "broad-spectrum penicillin antibiotics". It is an antibiotic that kills many types of bacteria. Tazobactam may prevent some bacteria that are not sensitive to piperacillin from surviving. This means that if piperacillin is given together with tazobactam, more strains of bacteria will be killed. Piperacillin/Tazobactam is used in adults and adolescents to treat bacterial infections:

• of the lower respiratory tract (lungs),
• of the urinary system (kidneys and bladder),
• of the abdominal cavity,
• of the skin and blood.

Piperacillin/Tazobactam can be used to treat bacterial infections in patients with a low number of white blood cells (i.e., with reduced resistance to infections). Piperacillin/Tazobactam is used in children aged 2 to 12 years to treat infections in the abdominal cavity, such as appendicitis, peritonitis (infection of the fluid and membrane lining the abdominal cavity), and gallbladder infections. Piperacillin/Tazobactam can be used to treat bacterial infections in patients with a low number of white blood cells (reduced resistance to infections). In some severe infections, the doctor may consider using Piperacillin/Tazobactam in combination with other antibiotics.

2. Important information before using Piperacillin/Tazobactam

When not to use Piperacillin/Tazobactam

• If you are allergic to piperacillin, tazobactam, or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to penicillin antibiotics, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to Piperacillin/Tazobactam.

Warnings and precautions

Before starting treatment with Piperacillin/Tazobactam, discuss with your doctor, pharmacist, or nurse:

• If you have allergies. If you are allergic to several allergens, you should inform your doctor or other healthcare professional before taking the medicine.
• If you have had diarrhea before treatment or if it occurs during or after treatment. In this case, you should immediately inform your doctor or other healthcare professional. Do not take any anti-diarrheal medicines without consulting your doctor first.
• If you have low potassium levels in your blood. It is possible that your doctor will assess your kidney function before starting treatment with this medicine and will order regular blood tests during treatment.
• If you have kidney or liver problems or if you are undergoing hemodialysis. It is possible that your doctor will assess your kidney function before starting treatment with this medicine and will order regular blood tests during treatment.
• If you are taking vancomycin antibiotic at the same time as Tazocin, the risk of kidney damage may be increased (see "Tazocin and other medicines").
• If you are taking blood-thinning medicines (anticoagulants or anti-coagulants) (see "Piperacillin/Tazobactam and other medicines") or if you experience unexpected bleeding during treatment. In this case, you should immediately inform your doctor or other healthcare professional.
• If you experience seizures during treatment. In this case, you should inform your doctor or other healthcare professional.
• If you think you have developed a new infection or if an existing infection has worsened. In this case, you should inform your doctor or other healthcare professional.

There have been reports of a disease in which the immune system produces too many normally normal white blood cells called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This disease can be life-threatening if not diagnosed and treated early. If you experience many symptoms such as fever, swollen lymph nodes, weakness, dizziness, shortness of breath, cyanosis, or skin rash, you should immediately contact your doctor.

Children

Piperacillin/Tazobactam should not be used in children under 2 years of age due to the lack of sufficient data on safety and efficacy.

Piperacillin/Tazobactam and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. Some medicines may interact with piperacillin and tazobactam. These include:

• A medicine used to treat gout (probenecid); it may prolong the time during which piperacillin and tazobactam are eliminated from the body.
• Medicines that prevent blood clotting or are used to treat blood clots (e.g., heparin, warfarin, aspirin).
• Medicines used to relax muscles during surgical procedures. If you are going to have general anesthesia, you should tell your doctor.
• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may prolong the time during which methotrexate is eliminated from the body.
• Medicines that lower potassium levels in the blood (e.g., certain diuretics or certain cancer medicines).
• Medicines containing other antibiotics, specifically tobramycin, gentamicin, or vancomycin. If you have kidney problems, you should tell your doctor. Taking Piperacillin/Tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if you do not have kidney problems.

Effect on laboratory tests If a blood sample is to be taken from you or if you need to provide a urine sample, you should tell the laboratory staff or your doctor that you are taking Piperacillin/Tazobactam.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine. Your doctor will decide whether Piperacillin/Tazobactam is suitable for you.
• Piperacillin and tazobactam may pass into the baby's body through the placenta or breast milk. If you are breastfeeding, your doctor will decide whether Piperacillin/Tazobactam is suitable for you.

Driving and using machines

Taking Piperacillin/Tazobactam is unlikely to affect your ability to drive or use machines.

Piperacillin/Tazobactam contains sodium

The maximum recommended daily dose of this medicine contains 864.8 mg of sodium (the main component of common salt). This corresponds to 43.24% of the maximum recommended daily intake of sodium in the diet for adults. Piperacillin/Tazobactam 2g/0.25g: If you are taking 4 or more vials per day for a long time, patients, especially those controlling their sodium intake, should consult their doctor or pharmacist.Piperacillin/Tazobactam 4g/0.5g: If you are taking 2 or more vials per day for a long time, patients, especially those controlling their sodium intake, should consult their doctor or pharmacist.

3. How to use Piperacillin/Tazobactam

This medicine is given to you by a doctor or other healthcare professional as an infusion (drip) into a vein.

Dosage

The dose of the medicine given to you will depend on the disease being treated, your age, and any kidney problems you may have.

Use in adults and adolescents over 12 years of age

The recommended dose is 4g + 0.5g of piperacillin and tazobactam every 6 to 8 hours given intravenously (directly into the blood).

Use in children aged 2 to 12 years

The recommended dose for children with abdominal infections is 100mg of piperacillin per kilogram of body weight and 12.5mg of tazobactam per kilogram of body weight every 8 hours given intravenously (directly into the blood). The recommended dose for children with a low number of white blood cells is 80mg of piperacillin per kilogram of body weight and 10mg of tazobactam per kilogram of body weight every 6 hours given intravenously (directly into the blood). Your doctor will calculate the dose of the medicine based on your child's body weight, with no single dose being greater than 4g of piperacillin and 0.5g of tazobactam. Piperacillin/Tazobactam will be given until the infection has cleared up (for a period of 5 to 14 days).

Patients with kidney disease

Your doctor may reduce the dose of Piperacillin/Tazobactam or the frequency of administration. Your doctor may also order regular blood tests to ensure that the dose of the medicine is correct, especially if it is necessary to use the medicine for a long time.

Using a higher dose of Piperacillin/Tazobactam than recommended

Since Piperacillin/Tazobactam will be given to you by a doctor or other healthcare professional, it is unlikely that you will receive the wrong dose. However, if you experience side effects, such as seizures, or if you think you have been given too high a dose, you should immediately inform your doctor.

Missing a dose of Piperacillin/Tazobactam

If you think that a dose of Piperacillin/Tazobactam has been missed, you should immediately inform your doctor or other healthcare professional. If you have any further questions about using 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. If you experience any of the following serious side effects, contact your doctor immediately.Serious side effects (frequency not known) of Piperacillin/Tazobactam include:

• Severe skin reactions [Stevens-Johnson syndrome, bullous skin rash (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)] initially appearing as reddened patches similar to targets or circular patches, often with centrally located blisters. Additional symptoms include ulcers in the mouth, throat, nose, limbs, genital areas, and conjunctivitis (redness and swelling of the eyes). The rash may develop into widespread blisters or peeling of the skin and may be life-threatening.
• A severe, potentially life-threatening allergic reaction (drug rash with eosinophilia and systemic symptoms), which may affect the skin and, more importantly, other organs under the skin, such as the kidneys and liver.
• Skin disease (acute generalized exanthematous pustulosis) with accompanying fever. This disease is characterized by numerous small blisters filled with fluid, located on a large area of swollen and reddened 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 rash or hives (uncommon), itching or rash on the skin (common).
• Yellowing of the skin or whites of the eyes (frequency not known).
• Blood cell damage [symptoms include: unexpected shortness of breath, red or brown urine (frequency not known), nosebleeds (rare), and small bruises (frequency not known)], significant reduction in the number of white blood cells (rare).
• Severe or persistent diarrhea with fever or weakness (rare).

If any of the followingside effects get worse or if you experience any side effects not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Very common(may affect more than 1 in 10 people):

• Diarrhea.

Common(may affect up to 1 in 10 people):

• Fungal infection.
• Reduced platelet count, reduced red blood cell count or hemoglobin, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time).
• Reduced protein levels in the blood.
• Headache, insomnia.
• Abdominal pain, vomiting, nausea, constipation, stomach upset.
• Increased liver enzyme activity in the blood.
• Skin rash, itching.
• Abnormal kidney function test results.
• Fever, infusion site reactions.

Uncommon(may affect up to 1 in 100 people):

• Reduced white blood cell count (leukopenia), prolonged clotting time (prolonged prothrombin time).
• Reduced potassium levels in the blood, reduced blood sugar levels, seizures observed in patients taking high doses of the medicine or with kidney problems.
• Low blood pressure, vein inflammation (feeling of excessive sensitivity to touch or redness of the inflamed area), skin redness.
• Increased bilirubin levels (a breakdown product of blood pigment).
• Skin reactions including redness, skin changes, hives.
• Joint and muscle pain.
• Chills.

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

• Significant reduction in the number of white blood cells (agranulocytosis), nosebleeds.
• Severe colitis, inflammation of the mucous membrane of the mouth.
• Shedding of the outer layer of the skin all over the body [toxic epidermal necrolysis (Lyell's syndrome)].

Not known(frequency cannot be estimated from the available data):

• Significant reduction in the number of red blood cells, white blood cells, and platelets (pancytopenia), reduction in the number of white blood cells (neutropenia), reduction in the number of red blood cells due to premature destruction or degradation, small bruises, prolonged bleeding time, increased platelet count, increased count of a specific type of white blood cells (eosinophilia).
• Allergic reaction and severe allergic reaction.
• Liver inflammation, yellowing of the skin and whites of the eyes.
• Severe allergic reaction affecting the whole body, with a rash on the skin and mucous membranes, blisters, and other skin lesions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs, such as the kidneys and liver (drug rash with eosinophilia and systemic symptoms), numerous small blisters filled with fluid located on a large area of swollen and reddened skin with fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous skin rash).
• Kidney damage and kidney problems.
• Lung disease with an increased number of eosinophils (a type of white blood cell) in the lungs.
• Sudden confusion and disorientation (delirium).

Administration of piperacillin has been associated with an increased incidence of fever and rash in patients with cystic fibrosis. Beta-lactam antibiotics, including piperacillin/tazobactam, may cause encephalopathy (brain disease) and seizures.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: +48 22 49 21 301; fax: +48 22 49 21 309; website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Piperacillin/Tazobactam

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 outer carton and vials after EXP. The expiry date refers to the last day of that month. Unopened vials: Store in a temperature not exceeding 25°C. Solution after reconstitution: The product has been shown to be chemically and physically stable for 24 hours when stored in a refrigerator at 2-8°C after reconstitution in one of the compatible solvents (see section 6). This medicinal product is for single use only. Any unused solution should be discarded. Solution after dilution: The reconstituted solution should be used within 24 hours when stored in a refrigerator at 2-8°C. The periods of storage of the solution after reconstitution and after dilution do not add up (i.e., the solution cannot be stored for 24 + 24 hours). From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions. Before administration, the solution should be inspected visually for particulate matter and changes in color. The solution should only be used if it is clear and free of particles. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 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 Piperacillin/Tazobactam contains

The active substances are piperacillin sodium and tazobactam sodium. One vial (30 mL) contains 2.085g of piperacillin sodium, equivalent to 2g of piperacillin, and 0.268g of tazobactam sodium, equivalent to 0.25g of tazobactam. Sodium content: 4.7 mmol (108.1 mg) of sodium per vial of powder for solution for infusion. One vial (30 mL) contains 4.17g of piperacillin sodium, equivalent to 4g of piperacillin, and 0.536g of tazobactam sodium, equivalent to 0.5g of tazobactam. Sodium content: 9.4 mmol (216.2 mg) of sodium per vial of powder for solution for infusion.

What Piperacillin/Tazobactam looks like and contents of the pack

Piperacillin/Tazobactam is a white or pale yellow crystalline powder. The medicine is dissolved in another solution by a doctor or nurse and given to you as an intravenous infusion. Each vial of Piperacillin/Tazobactam contains 2.25g of the medicine. Each vial of Piperacillin/Tazobactam contains 4.5g of the medicine. Piperacillin/Tazobactam is available in packs of 1, 5, 10, or 20 glass vials. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Noridem Enterprises Limited Evagorou & Makariou, Mitsi Building 3, Office 115, 1065 Nicosia, Cyprus.

Manufacturer

DEMO S.A. PHARMACEUTICAL INDUSTRY 21 km National Road Athens-Lamia, 14568 Krioneri, Attiki, Greece, T: +30 210 8161802, F: +30 2108161587.

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

Date of last revision of the leaflet: 02/2024

Information intended for healthcare professionals only:

Instructions for use

Piperacillin/Tazobactam will be given as an intravenous infusion (over 30 minutes).

Intravenous administration

The solution should be prepared by adding the appropriate volume of one of the following compatible solvents to the vial. The vial should be shaken until the powder is dissolved. The powder usually dissolves within 5 to 10 minutes of continuous shaking (detailed information on handling the medicine can be found below).

Contents of the vial * Volume of solvent added to the vial

2g + 0.25g (2g of piperacillin and 0.25g of tazobactam) 10 mL 4g + 0.50g (4g of piperacillin and 0.5g of tazobactam) 20 mL * Compatible solvents for reconstitution:

• 0.9% (9 mg/mL) sodium chloride solution for injection
• sterile water for injection
• 5% glucose solution.

The reconstituted solution should be withdrawn from the vial using a syringe. After reconstitution, the contents of the vial withdrawn with a syringe will contain the labeled amount of piperacillin and tazobactam. The solution can then be further diluted to the required volume (e.g., 50 mL or 150 mL) with one of the following compatible diluents:

• sterile water for injection
• 0.9% (9 mg/mL) sodium chloride solution for injection
• 5% glucose solution
• 6% dextran solution in 0.9% (9 mg/mL) sodium chloride solution

The maximum recommended volume of sterile water for injection is 50 mL per dose.

Incompatibilities

If Piperacillin/Tazobactam is given at the same time as another antibiotic (e.g., an aminoglycoside), these products must be given separately. Mixing beta-lactam antibiotics with aminoglycosides in vitromay cause significant inactivation of the aminoglycoside. Piperacillin/Tazobactam should not be mixed with other substances in a syringe or infusion bottle, as compatibility has not been established. Ringer's lactate solution (Hartmann's solution) is incompatible with the combination of piperacillin and tazobactam. Due to the chemical instability of Piperacillin/Tazobactam, it should not be used with solutions containing only sodium bicarbonate. Piperacillin/Tazobactam should not be added to blood products or albumin hydrolysates.

Concomitant administration of Piperacillin/Tazobactam with aminoglycosides

Mixing beta-lactam antibiotics with aminoglycosides in vitromay cause significant inactivation of the aminoglycoside, so Piperacillin/Tazobactam and the aminoglycoside should be given separately. If concomitant administration of an aminoglycoside and Piperacillin/Tazobactam is necessary, they should be reconstituted and diluted separately.

Do not mix or administer with aminoglycosides.

Do not reconstitute or dilute with Ringer's lactate solution (Hartmann's solution).

This medicinal product is for single use only. Reconstitution/dilution should be carried out under controlled and validated aseptic conditions. Before administration, the solution should be inspected visually for particulate matter and changes in color. The solution should only be used if it is clear and free of particles. Any unused product or waste material should be disposed of in accordance with local requirements. Displacement volumePiperacillin/Tazobactam 2g + 0.25g displaces 1.56 mL. Piperacillin/Tazobactam 4g + 0.5g displaces 3.12 mL.