Piperacillin/tazobactam polpharma

Package leaflet: Information for the patient

Warning! Keep the leaflet – the information on the immediate packaging is in a foreign language.
Piperacillin/Tazobactam Polpharma (Perasin)
4 g + 0.5 g, powder for solution for infusion
Piperacillinum + Tazobactamum
Piperacillin/Tazobactam Polpharma and Perasin are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

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

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

Piperacillin belongs to a group of medicines known as "broad-spectrum penicillins". It is an antibiotic that kills many types of bacteria. Tazobactam may prevent some bacteria resistant to piperacillin from surviving. This means that when piperacillin and tazobactam are used together, a greater number of bacterial strains are eradicated.
Piperacillin/Tazobactam Polpharma is used in adults and adolescents for the treatment of bacterial infections such as lower respiratory tract infections (lungs), urinary tract infections (kidneys and bladder), abdominal infections, skin infections, and blood infections. Piperacillin/Tazobactam Polpharma may also be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin/Tazobactam Polpharma is used in children aged 2 to 12 years for the treatment of abdominal infections such as appendicitis, peritonitis (infection of the fluid and membrane lining the abdominal organs), and cholecystitis (gallbladder infection). Piperacillin/Tazobactam Polpharma may also be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain severe infections, your doctor may consider administering Piperacillin/Tazobactam Polpharma together with other antibiotics.

2. Important information before using Piperacillin/Tazobactam Polpharma

When not to use Piperacillin/Tazobactam Polpharma

• if the patient is allergic to piperacillin or tazobactam, or to any of the other ingredients of this medicine (listed in section 6),
• if the patient is allergic to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin/Tazobactam Polpharma.

Warnings and precautions
Before starting treatment with Piperacillin/Tazobactam Polpharma, discuss with your doctor, pharmacist, or nurse if:

• the patient has allergies. If the patient has multiple allergies, they should ensure they have informed the doctor or other healthcare professional before taking the medicine.
• the patient has diarrhoea before treatment, or develops diarrhoea during or after treatment. Inform the doctor or other healthcare professional immediately. Do not take any anti-diarrhoeal medicines without consulting a doctor.
• the patient has low blood potassium levels. The doctor may check kidney function before administering the medicine and perform regular blood tests during treatment.
• the patient has kidney or liver disease, or is undergoing haemodialysis. The doctor may check kidney function before administering the medicine and perform regular blood tests during treatment.
• the patient is taking another antibiotic called vancomycin at the same time as piperacillin with tazobactam, as this may increase the risk of kidney damage (see also "Piperacillin/Tazobactam Polpharma and other medicines" in this leaflet).
• the patient is taking medicines to prevent excessive blood clotting, known as anticoagulants (see also "Piperacillin/Tazobactam Polpharma and other medicines" in this leaflet), or if unexpected bleeding occurs during treatment. In such cases, inform the doctor or other healthcare professional immediately.
• the patient experiences seizures during treatment. Inform the doctor or other healthcare professional immediately.
• the patient suspects a new infection has occurred or an existing infection has worsened. In such cases, inform the doctor or other healthcare professional.

Haemophagocytic lymphohistiocytosis
Cases of a condition in which the immune system produces excessive numbers of normally functioning white blood cells called histiocytes and lymphocytes, leading to an inflammatory state (haemophagocytic 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 with tazobactam is not recommended for use in children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin/Tazobactam Polpharma and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, including those obtained without a prescription.
Some medicines may interact with piperacillin and tazobactam. These include, among others:

• a medicine used to treat gout (probenecid); this may prolong the elimination of piperacillin and tazobactam 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 surgery. If the patient is to undergo general anaesthesia, they should inform the doctor about taking this medicine;
• a medicine used in cancer, joint inflammation, or psoriasis (methotrexate). Piperacillin and tazobactam may prolong the elimination of methotrexate from the body;
• medicines that reduce potassium levels in the blood (e.g. diuretics or certain medicines used in cancer treatment);
• medicines containing other antibiotics: tobramycin, gentamicin, or vancomycin. If the patient has kidney problems, they should inform the doctor. Concurrent use of piperacillin with tazobactam and vancomycin may increase the risk of kidney damage, even if the patient does not have kidney problems.

Effect on laboratory tests
If the patient is to provide a blood or urine sample, they should inform the doctor or other healthcare professional that they are taking Piperacillin/Tazobactam Polpharma.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or other healthcare professional before taking this medicine. The treating doctor will decide whether Piperacillin/Tazobactam Polpharma is the appropriate medicine for her.
Piperacillin and tazobactam may pass into the body of the unborn child or through human milk. If the patient is breastfeeding, the treating doctor will decide whether Piperacillin/Tazobactam Polpharma is appropriate for her.

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

Piperacillin/Tazobactam Polpharma contains sodium
This medicine contains 216 mg of sodium (the main component of table salt) per vial. This corresponds to 10.8% of the maximum recommended daily intake of sodium in the diet for adults. This should be taken into account if the patient is on a sodium-controlled diet.

3. How to use Piperacillin/Tazobactam Polpharma

This medicine will be administered by a doctor or other healthcare professional as an intravenous infusion (lasting 30 minutes).
Dosage
The dose given to the patient depends on the illness being treated, the patient's age, and any kidney problems the patient may have.
Adults and adolescents aged 12 years or older
The usual dose is 4 g + 0.5 g of piperacillin with tazobactam, administered intravenously (directly into the bloodstream) every 6 to 8 hours.
Children aged 2 to 12 years
For children with abdominal infections, the recommended dose is 100 mg + 12.5 mg of piperacillin with tazobactam per kg of body weight, administered intravenously (directly into the bloodstream) every 8 hours. The usual dose for children with low white blood cell counts is 80 mg + 10 mg of piperacillin with tazobactam per kg of body weight, administered intravenously (directly into the bloodstream) every 6 hours.
The doctor will calculate the dose based on the child's body weight, but each individual dose of Piperacillin/Tazobactam Polpharma will not exceed 4 g + 0.5 g.
The patient will receive Piperacillin/Tazobactam Polpharma until all signs of infection have completely resolved (for 5 to 14 days).
Patients with kidney problems
The doctor may recommend reducing the dose of Piperacillin/Tazobactam Polpharma or the frequency of administration. The doctor may perform blood tests to ensure the correct dose is being given, especially if the patient is receiving the medicine for a prolonged period.
Use of a higher than recommended dose of Piperacillin/Tazobactam Polpharma
Piperacillin/Tazobactam Polpharma will be administered by a doctor or other healthcare professional, so administration of an incorrect dose is unlikely. However, if the patient experiences adverse effects such as seizures, or if the patient believes they have received too high a dose, they should inform the doctor immediately.
Missed dose of Piperacillin/Tazobactam Polpharma
If the patient believes a dose of Piperacillin/Tazobactam Polpharma has been missed, they should inform the doctor or other healthcare professional immediately.
If there are any further doubts regarding the use of this medicine, consult the doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the potentially serious adverse reactions of
Piperacillin/Tazobactam Polpharma occur, you should immediately consult a doctor.
Serious adverse reactions (with frequency stated in parentheses) associated with
Piperacillin/Tazobactam Polpharma 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, typically on the trunk. Additionally, ulceration of the mouth, throat, nose, limbs, genital organs, and conjunctivitis (redness and swelling of the eyes) may occur. 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), which may affect the skin and, more importantly, internal organs such as the kidneys and liver,
• skin disease (acute generalized exanthematous pustulosis) accompanied by fever, manifesting as numerous small fluid-filled blisters on a swollen and red skin surface,
• swelling of the face, lips, tongue, or other body parts (frequency not known),
• shortness of breath, wheezing, or difficulty breathing (frequency not known),
• severe rash or urticaria (not common), itching or skin rash (common),
• yellowing of the skin or whites of the eyes (frequency not known),
• damage to blood cells [symptoms include: unexpected shortness of breath, red or brown discoloration of urine (frequency not known), nosebleeds (rare), small bruises (frequency not known), significant decrease in white blood cell count (rare)],
• severe or persistent diarrhoea with fever or weakness (rare). If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, you should inform your doctor or other healthcare professional.

Very common (may occur in more than 1 in 10 people):

• diarrhoea.

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

• fungal infections (candidiasis)
• decreased platelet count, decreased red blood cell count or haemoglobin levels, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time)
• decreased protein levels in blood
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, indigestion
• increased liver enzyme activity in blood
• skin rash, itching
• abnormal blood test results indicating kidney function
• fever, injection site reaction.

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

• decreased white blood cell count (leukopenia), prolonged blood 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 in those with kidney problems
• low blood pressure, phlebitis (increased sensitivity to touch or redness in the inflamed area), skin redness
• increased levels of breakdown product of blood pigment (bilirubin)
• skin reactions including redness, skin lesions, urticaria
• joint and muscle pain
• chills.

Rare (may occur in less than 1 in 1,000 people):

• marked decrease in white blood cell count (agranulocytosis), nosebleeds
• severe colitis, inflammation of the mucous membrane of the mouth (stomatitis)
• detachment of the outer layer of skin over the entire body (toxic epidermal necrolysis).

Frequency not known (frequency cannot be estimated from available data):

• marked decrease in red blood cells, white blood cells, and platelets (pancytopenia), decreased white blood cell count (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
• hepatitis, yellowing of the skin or whites of the eyes
• 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), numerous small fluid-filled blisters on a swollen and red skin surface accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
• impaired kidney function and kidney problems
• lung disease characterized by increased presence of eosinophils (a type of white blood cell) in the lungs
• acute disorientation and confusion (delirium).

Administration of piperacillin has been associated with increased incidence of fever and rash
in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin with tazobactam, may lead to symptoms of
brain function disturbances (encephalopathy) and seizures.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Piperacillin/Tazobactam Polpharma

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following: EXP.
The expiry date refers to the last day of the specified month.
Powder:
Unopened vials: Store below 25°C. Keep the vial in its original packaging to protect from light.
For single use only. Any unused solution should be discarded.
Reconstituted and diluted solutions of the medicine are physically compatible and chemically stable for
24 hours at controlled room temperature (25°C) and for 48 hours at 2°C - 8°C.
From a microbiological standpoint, reconstituted and diluted solutions should be used immediately.
If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user, and it should usually not exceed 24 hours at 2°C - 8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Piperacillin/Tazobactam Polpharma contains
The active substances in the medicine are piperacillin monohydrate and tazobactam.
Each vial of Piperacillin/Tazobactam Polpharma contains piperacillin monohydrate (as sodium piperacillin) in an amount equivalent to 4 g of piperacillin and tazobactam (as sodium tazobactam) in an amount equivalent to 0.5 g of tazobactam.
The medicine does not contain any other ingredients.

What Piperacillin/Tazobactam Polpharma looks like and contents of the pack
Powder for solution for infusion.
White or almost white powder.
Piperacillin/Tazobactam Polpharma is available in packs of 10 vials, enclosed in a cardboard box with a package leaflet included.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in Romania, the country of export:
Antibiotice S.A., Str. Valea Lupului nr. 1, 707410 Iași
Romania

Manufacturer:
Antibiotice S.A., Str. Valea Lupului nr. 1, 707410 Iași
Romania

Parallel Importer:
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański

Repackaged in:
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warszawa
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław

Marketing Authorisation Number in Romania, the country of export: 14648/2022/02
Parallel Import Licence Number: 188/25
[parallel importer's logo]

Information intended exclusively for medical professionals

Piperacillin/Tazobactam Polpharma (Perasin)
4 g + 0.5 g, powder for solution for infusion
Warning: Use in adult patients for treatment of bacteremia caused by E. coli and K. pneumoniae strains (ceftriaxone-resistant) producing extended-spectrum beta-lactamases (ESBL) is not recommended.
For slow intravenous infusion.
Pharmaceutical incompatibilities with solvents and other medicinal products

• Ringer's solution with lactates (Hartmann's solution) is pharmaceutically incompatible with Piperacillin/Tazobactam Polpharma and should not be administered simultaneously through a Y-type injection port.
• If Piperacillin/Tazobactam Polpharma is administered concurrently with another antibiotic (e.g. aminoglycosides), these medicinal products must be given separately. Mixing Piperacillin/Tazobactam Polpharma with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.
• Piperacillin/Tazobactam Polpharma must not be mixed with other medicinal products in a syringe or infusion bottle, as compatibility has not been established.
• Due to chemical instability, Piperacillin/Tazobactam Polpharma must not be used with solutions containing sodium bicarbonate.
• Piperacillin/Tazobactam Polpharma must not be added to blood products or albumin hydrolysates.

INSTRUCTIONS FOR USE, HANDLING, AND DISPOSAL
The medicinal product must be reconstituted and diluted under aseptic conditions. Before administration, inspect the solution for visible particulate matter and discoloration. The solution should only be administered if it is clear and free from visible particles.
Needle insertion into the rubber stopper – instructions:
To avoid coring of the stopper, when inserting the needle into the rubber stopper, it is recommended to use a needle with an outer diameter less than or equal to 0.8 mm. The needle should be inserted only in the center of the rubber stopper and perpendicularly.
For single use only. Any unused solution must be discarded.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.
Sterile diluents for preparing the solution after reconstitution:

• Water for injections
• 9 mg/mL (0.9%) sodium chloride solution for injection
• 50 mg/mL (5%) dextrose solution in water

Dilution guidelines (for intravenous infusion)
Each vial of Piperacillin/Tazobactam Polpharma 4 g + 0.5 g must be dissolved in 20 mL of one of the above diluents.
Rotate the vial until complete dissolution.
The reconstituted solution may be further diluted to the desired volume (e.g. 50 mL to 150 mL) within a concentration range of 26.67 + 3.33 mg/mL to 80 + 10 mg/mL using one of the following compatible diluents:

• 9 mg/mL (0.9%) sodium chloride solution for injection
• 50 mg/mL (5%) dextrose solution in water

SPECIAL PRECAUTIONS FOR STORAGE
Unopened vials: Store below 25°C. Keep the vial in its original packaging to protect from light.
Reconstituted and diluted solutions of the medicinal product are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and for 48 hours at 2°C – 8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user. Generally, the solution should not be stored for longer than 24 hours at 2°C – 8°C, unless reconstitution and dilution have been carried out under controlled and validated aseptic conditions.