PIPERACILLIN 4 g + 0.5 g Powder

Contents of the leaflet

1. PATIENT INFORMATION LEAFLET
2. Leaflet attached to the packaging: information for the user
3. Piperacillin/Tazobactam Noridem, 2g + 0.25g, powder for solution for infusion
4. Piperacillin/Tazobactam Noridem, 4 g + 0.5 g, powder for solution for infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. The medicine is known by one of the following names:
   3. Table of contents of the leaflet
5. What is Piperacillin/Tazobactam and what is it used for
6. Important information before using Piperacillin/Tazobactam
   1. When not to use Piperacillin/Tazobactam
   2. Warnings and precautions
   3. Children
   4. Piperacillin/Tazobactam and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Piperacillin/Tazobactam contains sodium
7. How to use Piperacillin/Tazobactam
   1. Dosage
   2. Use in adults and adolescents over 12 years of age
   3. Use in children aged 2 to 12 years
   4. Patients with kidney disease
   5. Overdose of Piperacillin/Tazobactam
   6. Missed dose of Piperacillin/Tazobactam
8. Possible side effects
   1. Reporting side effects
9. How to store Piperacillin/Tazobactam
10. Contents of the pack and other information
    1. What Piperacillin/Tazobactam contains
    2. What Piperacillin/Tazobactam looks like and contents of the pack
    3. Marketing authorization holder and manufacturer
    4. Marketing authorization holder
    5. Manufacturer
    6. This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
    7. Date of last revision of the leaflet: 02/2024 --------------------------------------------------------------------------------------------------------------------------
    8. Information intended for healthcare professionals only:
    9. Instructions for use
    10. Intravenous administration
    11. Contents of the vial * Volume of solvent added to the vial
    12. Incompatibilities
    13. Concomitant administration of Piperacillin/Tazobactam with aminoglycosides
    14. Do not mix or administer with aminoglycosides.
    15. Do not reconstitute or dilute with Ringer's lactate solution (Hartmann's solution).

PATIENT INFORMATION LEAFLET

Leaflet attached to the packaging: information for the user

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

Piperacillin/Tazobactam Noridem, 4 g + 0.5 g, 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.
• In case of any doubts, consult a doctor, pharmacist or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist or nurse. See section 4.

The medicine is known by one of the following names:

• Piperacillin/Tazobactam Noridem, 2 g + 0.25 g, Powder for solution for infusion
• Piperacillin/Tazobactam Noridem, 4 g + 0.5 g, 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 resistant 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 the patient is allergic to piperacillin, tazobactam or any of the other ingredients of this medicine (listed in section 6).
• If the patient is allergic to penicillin antibiotics, cephalosporins or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin/Tazobactam.

Warnings and precautions

Before starting treatment with Piperacillin/Tazobactam, the patient should discuss it with their doctor, pharmacist or nurse:

• If the patient has allergies. If the patient is allergic to several allergens, they should inform their doctor or other healthcare professional before taking the medicine.
• If the patient has had diarrhea before treatment or if it occurs during or after treatment. In this case, the patient should immediately inform their doctor or other healthcare professional. No anti-diarrheal medicines should be taken without consulting a doctor first.
• If the patient has low potassium levels in the blood. It is possible that the doctor will assess the patient's kidney function before starting treatment with this medicine and will order regular blood tests during treatment.
• If the patient has kidney or liver problems or is undergoing hemodialysis. It is possible that the doctor will assess the patient's kidney function before starting treatment with this medicine and will order regular blood tests during treatment.
• If the patient is taking vancomycin antibiotic at the same time as Tazocin, the risk of kidney damage may be increased (see "Tazocin and other medicines").
• If the patient is taking medicines to prevent excessive blood clotting (known as anticoagulant or anti-thrombotic medicines) (see "Piperacillin/Tazobactam and other medicines") or if unexpected bleeding occurs during treatment. In this case, the patient should immediately inform their doctor or other healthcare professional.
• If the patient experiences seizures during treatment. In this case, the patient should inform their doctor or other healthcare professional.
• If the patient thinks they have developed a new infection or if an existing infection has worsened. In this case, the patient should inform their 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 the patient experiences many symptoms such as fever, swollen lymph nodes, weakness, dizziness, shortness of breath, cyanosis or skin rash, they should immediately contact their 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

The patient should tell their doctor or pharmacist about all medicines they 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 reduce blood clotting or are used to treat blood clots (e.g., heparin, warfarin, aspirin).
• Medicines used to relax muscles during surgical procedures. If the patient is to be given general anesthesia, they should tell their 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 medicines used to treat cancer).
• Medicines containing other antibiotics, specifically tobramycin, gentamicin or vancomycin. If the patient has kidney problems, they should tell their doctor. Taking Piperacillin/Tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if there are no kidney problems.

Effect on laboratory test results If a blood sample is to be taken from the patient or if the patient is to provide a urine sample, they should inform the laboratory staff or doctor that they are taking Piperacillin/Tazobactam.

Pregnancy and breastfeeding

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

Driving and using machines

Taking Piperacillin/Tazobactam is unlikely to affect the patient's 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 the patient is taking 4 or more vials per day for a long time, especially patients controlling their sodium intake, they should consult their doctor or pharmacist.Piperacillin/Tazobactam 4g /0.5g:If the patient is taking 2 or more vials per day for a long time, especially patients controlling their sodium intake, they should consult their doctor or pharmacist.

3. How to use Piperacillin/Tazobactam

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

Dosage

The dose of the medicine given to the patient depends on the disease being treated, the patient's age and any kidney problems they may have.

Use in adults and adolescents over 12 years of age

The recommended dose is 4 g + 0.5 g 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 100 mg of piperacillin per kilogram of body weight and 12.5 mg 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 80 mg of piperacillin per kilogram of body weight and 10 mg of tazobactam per kilogram of body weight every 6 hours given intravenously (directly into the blood). The doctor will calculate the dose of the medicine based on the child's body weight, with no single dose exceeding 4 g of piperacillin and 0.5 g of tazobactam. Piperacillin/Tazobactam will be given until the infection symptoms have completely resolved (for a period of 5 to 14 days).

Patients with kidney disease

The doctor may reduce the dose of Piperacillin/Tazobactam or the frequency of administration. The doctor may also order regular blood tests to ensure that the dose of the medicine is correct, especially if the medicine needs to be taken for a long time.

Overdose of Piperacillin/Tazobactam

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

Missed dose of Piperacillin/Tazobactam

If the patient thinks that a dose of Piperacillin/Tazobactam has been missed, they should immediately inform their doctor or other healthcare professional. If the patient has any further doubts about using this medicine, they should consult their doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If the patient experiences any of the following serious side effects, they should immediately see a doctor.Serious side effects (with frequency) of Piperacillin/Tazobactam Noiridem include:

• Severe skin reactions [Stevens-Johnson syndrome, blistering skin rash (frequency not known), exfoliative dermatitis (frequency not known) toxic epidermal necrolysis (rare)] initially appearing as reddened patches with a shape similar to a target or round patches, often with centrally located blisters. Additional symptoms include ulcers in the mouth, throat, nose, limbs, genitals 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
• 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, swollen and reddened area of the 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 minor bruising (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 worsen or if the patient experiences any side effects not listed in the leaflet, they should inform their doctor, pharmacist or nurse. Very common(may affect more than 1 in 10 people):

• diarrhea

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

• thrush
• 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, injection 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 product of hemoglobin breakdown)
• skin reactions including redness, skin changes, hives
• joint and muscle pain
• chills

Rare(may affect up to 1 in 1000 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 damage or degradation, minor bruising, 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, swollen and reddened area of the skin with fever (acute generalized exanthematous pustulosis), skin reactions with blisters (blistering skin rash)
• kidney damage and kidney problems
• lung disease with an increased number of eosinophils (a type of white blood cell) in the lungs
• acute 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 with tazobactam, may cause symptoms of brain function disorders (encephalopathy) and seizures.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices and Biocides of the Office for Registration of Medicinal Products, Medical Devices and Biocides: 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 the medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the outer carton and vials after EXP. The expiry date refers to the last day of the month stated. Unopened vials: Store in a temperature below 25°C. Solution after reconstitution The chemical and physical stability of the medicine has been demonstrated for 24 hours when stored in a refrigerator at 2-8°C after reconstitution in one of the compatible solvents (see section 6). The medicine 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 after opening. If the product is not used immediately after opening, the responsibility for the storage conditions and storage period before administration lies with the user, but this period should not exceed 24 hours at a storage temperature of 2-8°C, unless reconstitution/dilution is performed under controlled and validated aseptic conditions. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the pack and other information

What Piperacillin/Tazobactam contains

The active substances of the medicine are piperacillin sodium and tazobactam sodium. One vial (30 mL) contains 2.085 g of piperacillin sodium, equivalent to 2 g of piperacillin, and 0.268 g of tazobactam sodium, equivalent to 0.25 g 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 4.17 g of piperacillin sodium, equivalent to 4 g of piperacillin, and 0.536 g of tazobactam sodium, equivalent to 0.5 g 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 light yellow crystalline powder. The medicine is dissolved in another solution by a doctor or nurse and given to the patient as an intravenous infusion. The reconstituted solution is 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.

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

2 g + 0.25 g (2 g of piperacillin and 0.25 g of tazobactam) 10 mL 4 g + 0.50 g (4g of piperacillin and 0.5 g 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 of the powder in the recommended manner, the contents of the vial withdrawn with a syringe will contain the amount of piperacillin and tazobactam stated on the label. The solution can 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) has been found to be 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).

The medicine is for single use only. Reconstitution/dilution should be performed under controlled and validated aseptic conditions. Before administration, the solution should be visually inspected for particulate matter and changes in color. The solution should only be administered 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 2 g + 0.25 g displaces 1.56 mL. Piperacillin/Tazobactam 4 g + 0.5 g displaces 3.12 mL.