Piperacillin/tazobactam Polpharma

Leaflet attached to the packaging: patient information

Warning! Keep the leaflet, information on the immediate packaging in a foreign language.

Piperacillin/Tazobactam Polpharma (Perasin)

4 g + 0,5 g, powder for solution for infusion

Piperacillin + Tazobactam
Piperacillin/Tazobactam Polpharma and Perasin are different trade names for the same medicine.

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

• Keep this leaflet, so that you can read it again if you need to.
• 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.

Table of contents of the leaflet:

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

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

Piperacillin belongs to a group of medicines called "broad-spectrum penicillins". 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 and tazobactam are given together, more strains of bacteria will be killed. Piperacillin/Tazobactam Polpharma is used in adults and adolescents to treat bacterial infections, such as lower respiratory tract infections (lungs), urinary tract infections (kidneys and bladder), abdominal cavity infections, skin and blood infections. Piperacillin/Tazobactam Polpharma can be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). Piperacillin/Tazobactam Polpharma is used in children aged 2 to 12 years to treat abdominal cavity infections, such as appendicitis, peritonitis (infection of the fluid and membrane inside the abdominal organs), and cholecystitis (infection of the gallbladder). Piperacillin/Tazobactam Polpharma can be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). In some severe infections, the doctor may consider giving Piperacillin/Tazobactam Polpharma together with other antibiotics.

2. Important information before taking Piperacillin/Tazobactam Polpharma

When not to take 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 called penicillins, cephalosporins, or to other beta-lactamase inhibitors, as they may be allergic to Piperacillin/Tazobactam Polpharma.

Warnings and precautions

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

• the patient has allergies. If the patient has multiple allergies, they should make sure to tell their doctor or other healthcare professional about them before taking the medicine.
• the patient has diarrhea before treatment or if it occurs during or after treatment. The patient should immediately inform their doctor or other healthcare professional about it. The patient should not take any diarrhea medication without consulting their doctor.
• the patient has low potassium levels in the blood. It is possible that the doctor will check the patient's kidneys and perform regular blood tests during treatment.
• the patient has kidney or liver disease or is undergoing hemodialysis. It is possible that the doctor will check the patient's kidneys 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 blood-thinning medicines (anticoagulants) (see also "Piperacillin/Tazobactam Polpharma and other medicines" in this leaflet) or if unexpected bleeding occurs during treatment. The patient should immediately tell their doctor or other healthcare professional about it.
• the patient experiences seizures during treatment. The patient should immediately tell their doctor or other healthcare professional about it.
• the patient thinks they have a new infection or that an existing infection has worsened. In this case, the patient should tell their doctor or other healthcare professional about it.

Hemophagocytic lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many normally harmless 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, feeling weak, dizziness, shortness of breath, bluish discoloration, or skin rash, they should immediately contact their doctor.

Children

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

Piperacillin/Tazobactam Polpharma and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or might take, including those that are available without a prescription. Some medicines may interact with piperacillin and tazobactam. These include:

• medicines used to treat gout (probenecid); they may prolong the time it takes for piperacillin and tazobactam to be removed from the body;
• blood-thinning medicines or medicines used to treat blood clots (e.g., heparin, warfarin, aspirin);
• medicines used to relax muscles during surgery. If the patient is going to have general anesthesia, they should tell their doctor about taking this medicine.
• medicines used to treat cancer, arthritis, or psoriasis (methotrexate). Piperacillin and tazobactam may prolong the time it takes for methotrexate to be removed from the body.
• medicines that lower potassium levels in the blood (e.g., diuretics or certain cancer medicines);
• medicines that contain other antibiotics: tobramycin, gentamicin, or vancomycin. If the patient has kidney problems, they should tell their doctor. Taking piperacillin with tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if the patient does not have kidney problems.

Effect on laboratory tests

If the patient is going to have a blood or urine test, they should tell their doctor or other healthcare professional that they are taking Piperacillin/Tazobactam Polpharma.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or other healthcare professional before taking this medicine. The doctor will decide whether Piperacillin/Tazobactam Polpharma is suitable for the patient. Piperacillin and tazobactam may pass into the body of the unborn child or into breast milk. If the patient is breastfeeding, the doctor will decide whether Piperacillin/Tazobactam Polpharma is suitable for the patient.

Driving and using machines

Taking Piperacillin/Tazobactam Polpharma is unlikely to affect the patient's ability to drive or use machines.

Piperacillin/Tazobactam Polpharma contains sodium

The medicine contains 216 mg of sodium (the main component of common salt) per vial. This is equivalent 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 controlled sodium diet.

3. How to take Piperacillin/Tazobactam Polpharma

This medicine will be given to the patient by a doctor or other healthcare professional by intravenous infusion (lasting 30 minutes). 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.

Adult patients and adolescents aged 12 years and older

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

Children aged 2 to 12 years

For children with abdominal cavity infections, the recommended dose is 100 mg + 12.5 mg of piperacillin with tazobactam per kilogram of body weight, given intravenously (directly into the blood) every 8 hours. The usual dose for children with a low white blood cell count is 80 mg + 10 mg of piperacillin with tazobactam per kilogram of body weight, given intravenously (directly into the blood) 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 the infection symptoms have completely disappeared (for 5 to 14 days).

Patients with kidney disease

The doctor may recommend reducing the dose of Piperacillin/Tazobactam Polpharma or the frequency of administration. It is possible that the doctor will perform blood tests to ensure that the correct dose of the medicine is being given, especially if the patient is taking the medicine for a long time.

Overdose of Piperacillin/Tazobactam Polpharma

Piperacillin/Tazobactam Polpharma will be given to the patient by a doctor or other healthcare professional, so it is unlikely that the wrong dose will be given. However, if the patient experiences side effects, such as seizures, or thinks they have received too much medicine, they should immediately tell their doctor.

Missed dose of Piperacillin/Tazobactam Polpharma

If the patient thinks they have missed a dose of Piperacillin/Tazobactam Polpharma, they should immediately tell their doctor or other healthcare professional. If the patient has any further doubts about taking this medicine, they should consult their doctor or nurse.

4. Possible side effects

Like all medicines, Piperacillin/Tazobactam Polpharma can cause side effects, although not everybody gets them. If the patient experiences any of the following serious side effects, they should immediately contact their doctor. Serious side effects of Piperacillin/Tazobactam Polpharma (frequency in brackets) 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 target-like shape or round patches, often with centrally located blisters, occurring on the torso. Additionally, there may be 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.
• 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, which manifests as 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),
• shallow breathing, 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 white blood cell count (rare)],
• severe or persistent diarrhea with fever or weakness (rare). If the patient experiences any of these side effects or any other side effects not listed in this leaflet, they should tell their doctor or other healthcare professional.

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

• diarrhea. Common(may affect up to 1 in 10 people):
• fungal infections
• 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, indigestion
• increased liver enzyme activity in the blood
• skin rash, itching
• abnormal kidney function test results
• fever, reaction at the injection site.

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

• reduced white blood cell count (leukopenia), prolonged blood 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 in the blood
• skin reactions involving redness, skin changes, hives
• joint and muscle pain
• chills.

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

• significant reduction in white blood cell count (agranulocytosis), nosebleeds
• severe colitis, mouth ulcers
• shedding of the outer layer of the skin all over the body (toxic epidermal necrolysis).

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

• significant reduction in red blood cell count, white blood cell count, and platelet count (pancytopenia), reduced white blood cell count (neutropenia), reduced red blood cell count due to premature destruction or degradation, minor bruising, prolonged bleeding time, increased platelet count, increased eosinophil count
• allergic reaction and severe allergic reaction
• liver inflammation, yellowing of the skin or 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, accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (blistering skin rash)
• kidney problems and impaired kidney function
• pulmonary disease, in which eosinophils (a type of white blood cell) appear in the lungs in increased numbers
• 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 this 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, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. By reporting side effects, more information can be gathered 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 after EXP. The expiry date refers to the last day of the month stated. Powder: Unopened vials: Store in a temperature below 25°C. Store the vial in its original packaging to protect it from light. For single use only. 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 48 hours at a temperature of 2°C - 8°C. From a microbiological point of view, the reconstituted and diluted solutions should be used immediately. If not used immediately, the user is responsible for the storage conditions before use, and usually, the solution should not be stored for more than 24 hours at a temperature of 2°C - 8°C, unless the reconstitution and dilution were 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 that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Piperacillin/Tazobactam Polpharma contains

The active substances of the medicine are piperacillin monohydrate and tazobactam. Each vial of Piperacillin/Tazobactam Polpharma contains piperacillin monohydrate (in the form of piperacillin sodium) equivalent to 4 g of piperacillin and tazobactam (in the form of tazobactam sodium) 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, closed in a cardboard box with a leaflet attached to the packaging. For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization 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 by:

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 authorization number in Romania, the country of export: 14648/2022/02

Parallel import authorization number: 188/25

Date of leaflet approval: 26.05.2025

[parallel importer's logo]

Information intended for healthcare professionals only

Piperacillin/Tazobactam Polpharma (Perasin)

4 g + 0.5 g, powder for solution for infusion

Note: It is not recommended to use in adult patients for the treatment of bacteremia caused by E. coliand K. pneumoniae(resistant to ceftriaxone) producing extended-spectrum beta-lactamases (ESBL).

For slow intravenous infusion.

Incompatibilities with solvents and other medicines

• Ringer's solution with lactates (Hartmann's solution) is physically incompatible with Piperacillin/Tazobactam Polpharma and should not be administered simultaneously through a Y-type injection port.
• If Piperacillin/Tazobactam Polpharma is administered together with another antibiotic (e.g., aminoglycosides), the medicines should be administered separately. Mixing Piperacillin/Tazobactam Polpharma with an aminoglycoside in vitromay cause significant inactivation of the aminoglycoside.
• Piperacillin/Tazobactam Polpharma should 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 should not be used with solutions containing sodium bicarbonate.
• Piperacillin/Tazobactam Polpharma should not be added to blood products or albumin hydrolysates.

INSTRUCTIONS FOR USE, HANDLING, AND DISPOSAL

The medicine should be reconstituted and diluted under aseptic conditions. Before administration, the solution should be inspected for visible particles and color changes. The solution should only be administered if it is clear and free of visible particles.

Instructions for inserting the needle into the rubber stopper:

To avoid the core phenomenon, when reconstituting the product, it is recommended to use a needle with an outer diameter of less than or equal to 0.8 mm. The needle should be inserted only in the center of the rubber stopper, in a vertical direction. For single use only. Unused solution should be discarded. All unused medicinal products or waste materials should be disposed of in accordance with local regulations. Sterile diluents for preparing the solution after reconstitution:

• Sterile water for injections
• 9 mg/mL (0.9%) sodium chloride solution for injections
• 50 mg/mL (5%) glucose solution in water

Guidelines for dilution (for intravenous infusion)

Each vial of Piperacillin/Tazobactam Polpharma, 4 g + 0.5 g, should be dissolved in 20 mL of the above diluents. The vial should be shaken until the solution is dissolved. The reconstituted solution can be further diluted to the desired volume (e.g., 50 mL to 150 mL) within the concentration range of 26.67 + 3.33 mg/mL to 80 + 10 mg/mL using one of the following compatible solvents:

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

SPECIAL PRECAUTIONS FOR STORAGE

Unopened vials: Store in a temperature below 25°C. Store the vial in its original packaging to protect it 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 48 hours at a temperature of 2°C - 8°C. From a microbiological point of view, the medicinal product should be used immediately. If the medicinal product is not used immediately, the user is responsible for the storage conditions before use. Usually, the solution should not be stored for more than 24 hours at a temperature of 2°C - 8°C, unless the reconstitution and dilution were performed under controlled and validated aseptic conditions.