Piperacillin/tazobactam noridem

Package leaflet: Information for the user

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
piperacillin + tazobactam
Please read all of this leaflet carefully before this medicine is administered because it contains
important information for you.

• 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 personally. 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.
• This medicine is known as 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 remainder of this leaflet, the medicine will be referred to as Piperacillin/Tazobactam.

Leaflet contents

1. What Piperacillin/Tazobactam is and what it is used for
2. What you need to know before you are given Piperacillin/Tazobactam
3. How Piperacillin/Tazobactam is given
4. Possible side effects
5. How to store Piperacillin/Tazobactam
6. Contents of the pack and other information

1. What Piperacillin/Tazobactam is and what it is 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 when piperacillin is given together with tazobactam, more strains of bacteria are killed.
Piperacillin/Tazobactam is used in adults and adolescents for the treatment of bacterial infections of:

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

Piperacillin/Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (i.e. reduced resistance to infections).
Piperacillin/Tazobactam is used in children aged 2 to 12 years for the treatment of intra-abdominal infections, such as appendicitis, peritonitis (infection of the fluid within the abdominal cavity and the membrane lining the abdominal cavity), and infections of the gallbladder. Piperacillin/Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain serious infections, your doctor may consider using Piperacillin/Tazobactam together 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 penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin/Tazobactam.

Warnings and precautions
Before starting treatment with Piperacillin/Tazobactam, discuss this with the doctor,
pharmacist, or nurse:

• If the patient has allergies. If the patient is allergic to multiple allergens, they should inform the doctor or other healthcare professional before taking this medicine.
• If the patient has diarrhoea before treatment or if diarrhoea develops during or after treatment. In such a case, the patient should immediately inform the doctor or other healthcare professional. Do not take any medicines for diarrhoea without first consulting a doctor.
• If the patient has low blood potassium levels. The doctor may assess kidney function before starting treatment and may order regular blood tests during treatment.
• If the patient has kidney or liver problems or is undergoing haemodialysis. The doctor may assess kidney function before starting treatment and may order regular blood tests during treatment.
• If the patient is taking vancomycin at the same time as Tazocin, the risk of kidney damage may be increased (see section "Tazocin and other medicines").
• If the patient is taking medicines used to prevent excessive blood clotting (known as anticoagulants or antithrombotic agents) (see section "Piperacillin/Tazobactam and other medicines") or if unexpected bleeding occurs during treatment. In such a case, the patient should immediately inform the doctor or other healthcare professional.
• If the patient experiences seizures during treatment. In such a case, inform the doctor or other healthcare professional.
• If the patient suspects they have developed a new infection or worsening of an existing infection. In such a case, inform the doctor or other healthcare professional.

Cases of a disease in which the immune system produces too many normally functioning white blood cells called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis), have been reported. This condition may be life-threatening if not diagnosed and treated early. If multiple symptoms occur, such as fever, swollen lymph nodes, feeling weak, dizziness, shortness of breath, cyanosis, or skin rash, contact a doctor immediately.

Children
Piperacillin/Tazobactam is not recommended for children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin/Tazobactam and other medicines
Inform the doctor or pharmacist about all medicines currently used, recently used, or planned for use. Some medicines may interact with piperacillin and tazobactam. These include:

• A medicine used for 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 undergo general anaesthesia, they should inform the 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 inform the doctor. Concurrent use of Piperacillin/Tazobactam and vancomycin may increase the risk of kidney damage, even if there are no kidney problems.

Effect on laboratory tests
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, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or nurse before using this medicine. The doctor will then decide whether Piperacillin/Tazobactam is appropriate for her.
• 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 appropriate for her.

Driving and operating machinery
Treatment with Piperacillin/Tazobactam is unlikely to affect the ability to drive or operate machinery.

Piperacillin/Tazobactam contains sodium
The maximum recommended daily dose of this medicine contains 864.8 mg of sodium (the main component of table salt). This corresponds to 43.24% of the maximum recommended daily dietary sodium intake for adults.

Piperacillin/Tazobactam 2g /0.25g:
If 4 or more vials are taken per day for a prolonged period, patients, especially those monitoring sodium intake in their diet, should contact their doctor or pharmacist.

Piperacillin/Tazobactam 4g /0.5g:
If 2 or more vials are taken per day for a prolonged period, patients, especially those monitoring sodium intake in their diet, should contact their doctor or pharmacist.

3. How to use Piperacillin/Tazobactam Noridem

This medicine will be administered by a doctor or other healthcare professional as an intravenous infusion (a 30-minute drip) into a vein.
Dosage
The dose of medicine given to the patient depends on the illness being treated, the patient's age, and any kidney problems the patient 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, administered intravenously every 6 to 8 hours (directly into the bloodstream).
Use in children aged 2 to 12 years
The recommended dose for children with intra-abdominal infections is 100 mg of piperacillin per kilogram of body weight and 12.5 mg of tazobactam per kilogram of body weight, administered intravenously every 8 hours (directly into the bloodstream). The recommended dose for children with low white blood cell counts is 80 mg of piperacillin per kilogram of body weight and 10 mg of tazobactam per kilogram of body weight, administered intravenously every 6 hours (directly into the bloodstream).
The doctor will calculate the dose based on the child's body weight, ensuring that no single dose exceeds 4 g of piperacillin and 0.5 g of tazobactam.
Piperacillin/Tazobactam Noridem will be administered until complete resolution of infection symptoms (for a period of 5 to 14 days).
Patients with kidney disease
The doctor may reduce the dose of Piperacillin/Tazobactam Noridem or the frequency of administration. Blood tests may also be ordered to ensure the dose is appropriate, especially if prolonged treatment is required.
Administration of a higher than recommended dose of Piperacillin/Tazobactam Noridem
Since Piperacillin/Tazobactam Noridem will be administered by a doctor or other healthcare professional, it is unlikely that the patient will receive an incorrect dose.
However, if the patient experiences adverse effects such as seizures, or if the patient feels that too high a dose has been administered, they should immediately inform the doctor.
Missed dose of Piperacillin/Tazobactam Noridem
If the patient suspects that a dose of Piperacillin/Tazobactam Noridem has not been administered, they should immediately inform the doctor or other healthcare professional.
If in doubt about any aspect of the use of this medicine, consult the doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
If any of the serious adverse effects listed below occur, you should seek immediate medical advice.
Serious adverse effects (with frequency in brackets) of Piperacillin/Tazobactam Noridem include:

• Severe skin reactions [Stevens-Johnson syndrome, bullous dermatitis (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)] – initially appearing as red spots resembling targets or circular lesions, often with centrally located blisters. Additional symptoms include mucosal ulcerations in the mouth, throat, nose, limbs, genital organs, and conjunctivitis (redness and swelling of the eyes). The rash may progress to extensive blistering or skin peeling and may be life-threatening.
• Severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms – DRESS), which may affect the skin and, more importantly, other internal organs such as the kidneys and liver.
• Skin disease (acute generalized exanthematous pustulosis) accompanied by fever. This condition is characterized by numerous small fluid-filled blisters on a swollen and reddened large skin surface area.
• 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 (not common), itching or skin rash (common).
• Yellowing of the skin or whites of the eyes (frequency not known).
• Blood cell damage [symptoms include: sudden shortness of breath, red or brown urine (frequency not known), nosebleeds (rare), and small bruises (frequency not known)], significant decrease in white blood cells (rare).
• Severe or persistent diarrhoea with fever or weakness (rare).

If any of the following adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor, pharmacist, or nurse.
Very common (may affect more than 1 in 10 people):

• Diarrhoea

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

• Fungal infection (candidiasis)
• Decreased platelet count, decreased red blood cell count or blood pigment / haemoglobin, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time)
• Decreased blood protein levels
• Headache, insomnia
• Abdominal pain, vomiting, nausea, constipation, gastrointestinal discomfort
• Increased liver enzyme activity in blood
• Skin rash, itching
• Abnormal blood test results indicating kidney function abnormalities
• Fever, injection site reactions

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

• Decreased white blood cell count (leukopenia), prolonged clotting time (prolonged prothrombin time)
• Decreased potassium levels in blood, decreased blood glucose levels, seizures observed in patients receiving high doses of the medicine or with kidney problems
• Low blood pressure, phlebitis (increased sensitivity to touch or redness in the inflamed area), skin redness
• Increased bilirubin levels (a breakdown product of blood pigment)
• Skin reactions including redness, skin changes, urticaria
• Joint and muscle pain
• Chills

Rare (may affect up to 1 in 1000 people):

• Marked decrease in white blood cells (agranulocytosis), nosebleeds
• Severe inflammation of the large intestine (colitis), inflammation of the mucous membrane of the mouth (stomatitis)
• Detachment of the outer layer of skin over the entire body [toxic epidermal necrolysis (Lyell’s syndrome)]

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

• Marked decrease in red blood cells, white blood cells, and platelets (pancytopenia), decreased white blood cells (neutropenia), decreased red blood cells due to premature destruction or degradation, minor bruising, prolonged bleeding time, increased platelet count, increased number of a specific type of white blood cells (eosinophilia)
• Allergic reaction and severe allergic reaction
• Inflammation of the liver (hepatitis), yellowing of the skin and whites of the eyes (jaundice)
• Severe systemic allergic reaction with skin rash and mucous membrane lesions, blisters, and other skin eruptions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs such as kidneys and liver (drug reaction with eosinophilia and systemic symptoms – DRESS), numerous small fluid-filled blisters on a swollen and reddened large skin surface accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
• Impaired kidney function and kidney problems
• Lung disease with increased eosinophils in the lungs (a type of white blood cells)
• Acute disorientation and confusion (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 dysfunction (encephalopathy) and seizures.

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or nurse. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Piperacillin/Tazobactam Noridem

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 stated month.

Unopened vials: Store below 25°C.

Reconstituted solution:
The medicine has been shown to remain chemically and physically stable for up to 24 hours if stored in a refrigerator at 2–8°C after reconstitution with one of the compatible solvents (see section 6). The medicine is for single use only. Any unused portion of the solution must be discarded.

Diluted solution:
The reconstituted and subsequently diluted solution must be used within 24 hours if stored in a refrigerator at 2–8°C. The storage periods for reconstituted and diluted solutions are not cumulative (i.e., the solution cannot be stored for 24 + 24 hours).

From a microbiological standpoint, the product should be used immediately after opening. If the product is not used immediately, the user is responsible for ensuring appropriate storage duration and conditions prior to administration, not exceeding 24 hours at a storage temperature of 2–8°C, unless reconstitution/dilution was performed under controlled and validated aseptic conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Piperacillin/Tazobactam contains
The active substances in this medicine are piperacillin sodium and tazobactam sodium.
One vial (with a capacity of 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 (with a capacity of 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. This medicine is dissolved in another solution by a doctor or nurse and administered to the patient as an intravenous infusion (drip).
One vial of Piperacillin/Tazobactam contains 2.25 g of the medicine.
One vial of Piperacillin/Tazobactam contains 4.5 g of the medicine.
Piperacillin/Tazobactam is available in packs containing 1, 5, 10 or 20 glass vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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 authorised for marketing in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Information intended exclusively for healthcare professionals:

Instructions for use
The Piperacillin/Tazobactam Noridem medication will be administered by intravenous infusion (intravenous drip over 30 minutes).
Intravenous administration
Reconstitute the vial by adding the appropriate volume of one of the compatible diluents listed below. Rotate the vial until the powder is completely dissolved. The powder usually dissolves within 5 to 10 minutes of continuous rotation (detailed handling instructions are provided below).

| Vial content | * Volume of diluent to be added | |--------------|----------------------------------| | 2 g + 0.25 g (2 g piperacillin and 0.25 g tazobactam) | 10 mL | | 4 g + 0.50 g (4 g piperacillin and 0.5 g tazobactam) | 20 mL |

* Compatible reconstitution solvents:

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

After reconstitution, withdraw the solution from the vial using a syringe. Following proper reconstitution, the solution withdrawn from the vial will contain the amount of piperacillin and tazobactam stated on the label.

The reconstituted solution may be further diluted to the required volume (e.g., 50 mL or 150 mL) using one of the following compatible diluents:

• sterile water for injection
• 0.9% (9 mg/mL) sodium chloride injection
• 5% glucose solution
• 6% dextran 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 Noridem is administered simultaneously with another antibiotic (e.g., an aminoglycoside), these products must be given separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.
Piperacillin/Tazobactam Noridem must not be mixed with other medicinal products in the same syringe or infusion bottle, as compatibility has not been established.

Ringer's lactate (Hartmann's solution) is pharmaceutically incompatible with the combination of piperacillin and tazobactam.
Due to the chemical instability of Piperacillin/Tazobactam Noridem, it must not be used with solutions containing only sodium bicarbonate.
Do not add Piperacillin/Tazobactam Noridem to blood products or albumin hydrolysates.

Concomitant administration of Piperacillin/Tazobactam Noridem with aminoglycosides
Mixing beta-lactam antibiotics with aminoglycosides in vitro may lead to significant inactivation of aminoglycosides. Therefore, it is recommended that Piperacillin/Tazobactam Noridem and aminoglycosides be administered separately. If concomitant administration is necessary, the products should be reconstituted and diluted separately.

• Do not mix or administer together with aminoglycosides.
• Do not reconstitute or dilute using Ringer's lactate (Hartmann's solution).

This medicinal product is for single use only. Reconstitution and dilution must be performed under controlled and validated aseptic conditions. Prior to administration, visually inspect the solution for particulate matter and discoloration. The solution should only be administered if it is clear and free from particulate matter. Any unused product or waste material should be disposed of in accordance with local regulations.

Displacement volume
Piperacillin/Tazobactam Noridem 2 g + 0.25 g displaces 1.56 mL.
Piperacillin/Tazobactam Noridem 4 g + 0.5 g displaces 3.12 mL.