Piperacillin/tazobactam sandoz 4 g/0,5 g

Package leaflet: Information for the patient

Piperacillin/Tazobactam Sandoz 4 g/0.5 g
4 g + 500 mg, powder for solution for infusion
Piperacillinum + Tazobactamum
Please read all of this leaflet carefully before this medicine is administered, as it contains
important information for you.

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

Contents of the leaflet

1. What Piperacillin/Tazobactam Sandoz 4 g/0.5 g is and what it is used for
2. What you need to know before you are given Piperacillin/Tazobactam Sandoz 4 g/0.5 g
3. How to use Piperacillin/Tazobactam Sandoz 4 g/0.5 g
4. Possible side effects
5. How to store Piperacillin/Tazobactam Sandoz 4 g/0.5 g
6. Contents of the pack and other information

1. What Piperacillin/Tazobactam Sandoz 4 g/0.5 g is and what it is used for

Piperacillin is a broad-spectrum penicillin antibiotic. It can destroy many types of bacteria. Tazobactam can prevent certain bacteria resistant to piperacillin from surviving. This means that when piperacillin and tazobactam are given together, a wider range of bacteria are destroyed.
Piperacillin/Tazobactam Sandoz 4 g/0.5 g 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, or blood infections. Piperacillin/Tazobactam Sandoz 4 g/0.5 g may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin/Tazobactam Sandoz 4 g/0.5 g is used in children aged 2 to 12 years for the treatment of abdominal infections such as appendicitis, peritonitis (inflammation of the membrane lining the abdominal cavity), and cholecystitis (inflammation of the gallbladder). Piperacillin/Tazobactam Sandoz 4 g/0.5 g may 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 using Piperacillin/Tazobactam Sandoz 4 g/0.5 g in combination with other antibiotics.

2. Important information before using Piperacillin/Tazobactam Sandoz 4 g/0.5 g

When not to use Piperacillin/Tazobactam Sandoz 4 g/0.5 g
if the patient is allergic to piperacillin or tazobactam.
if the patient is allergic to antibiotics such as penicillins, cephalosporins or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin/Tazobactam Sandoz 4 g/0.5 g.

Warnings and precautions
Please discuss with your doctor, pharmacist or nurse if, before, during or after treatment with Piperacillin/Tazobactam Sandoz 4 g/0.5 g:
the patient has an allergy. If the patient has multiple allergies, they must inform the doctor or other healthcare professional before receiving the medicine.
the patient develops diarrhoea before starting, during or after completion of treatment. The doctor or other healthcare professional should be contacted immediately. Do not take any anti-diarrhoeal medicine without first consulting a doctor.
the patient has low blood potassium levels. The doctor may recommend kidney function tests before treatment and regular blood tests during treatment.
the patient is taking the antibiotic vancomycin at the same time as Piperacillin/Tazobactam Sandoz 4 g/0.5 g, as this may increase the risk of kidney damage (see also "Piperacillin/Tazobactam Sandoz 4 g/0.5 g and other medicines" in this leaflet).
the patient has impaired kidney or liver function or is undergoing haemodialysis. The doctor may recommend kidney monitoring before starting treatment and regular blood tests during treatment.
the patient is taking certain medicines (i.e. anticoagulants) to prevent excessive blood clotting (see also "Piperacillin/Tazobactam Sandoz 4 g/0.5 g and other medicines" in this leaflet) or experiences unexpected bleeding during treatment. In such a case, contact the doctor or other healthcare professional immediately.
the patient experiences seizures during treatment. In this case, inform the doctor or other healthcare professional.
the patient feels that a new infection has developed or an existing infection has worsened. In such a case, inform the doctor or other healthcare professional.

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

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

Piperacillin/Tazobactam Sandoz 4 g/0.5 g and other medicines
Tell your doctor or other healthcare professional about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription. Some medicines may interact with piperacillin and tazobactam.
These include, among others:
a medicine used to treat gout (probenecid); it may prolong the elimination of piperacillin and tazobactam from the body;
medicines used to reduce blood clotting or to treat blood clots (e.g. heparin, warfarin or acetylsalicylic acid);
medicines used to relax muscles during surgery; if the patient is to undergo general anaesthesia, they should inform the doctor about taking Piperacillin/Tazobactam Sandoz 4 g/0.5 g;
methotrexate (a medicine used to treat cancer, arthritis or psoriasis); 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 anticancer medicines);
medicines containing other antibiotics: tobramycin, gentamicin or vancomycin; if the patient has impaired kidney function, inform the doctor. Concurrent use of Piperacillin/Tazobactam Sandoz 4 g/0.5 g and vancomycin may increase the risk of kidney damage, even if there are no kidney problems.

Effect on laboratory test results
If the patient is to provide a blood or urine sample, they should inform the doctor or laboratory staff about the use of Piperacillin/Tazobactam Sandoz 4 g/0.5 g.

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 other healthcare professional before using this medicine.
The doctor will decide whether Piperacillin/Tazobactam Sandoz 4 g/0.5 g is appropriate for her.
Piperacillin and tazobactam may pass into the unborn child's body or into breast milk. The doctor will decide whether Piperacillin/Tazobactam Sandoz 4 g/0.5 g can be administered to a pregnant or breastfeeding woman.

Driving and operating machinery
Treatment with Piperacillin/Tazobactam Sandoz 4 g/0.5 g should not affect the ability to drive or operate machinery.

Piperacillin/Tazobactam Sandoz 4 g/0.5 g contains sodium
Piperacillin/Tazobactam Sandoz 4 g/0.5 g contains 217 mg of sodium (the main component of table salt) per dose. This corresponds to 11% of the maximum recommended daily dietary sodium intake for adults.
This amount should be taken into account in patients on a low-salt diet.

3. How to use Piperacillin/Tazobactam Sandoz 4 g/0.5 g

Piperacillin/Tazobactam Sandoz 4 g/0.5 g is administered to the patient by a doctor or other healthcare professional as an infusion (a 30-minute intravenous drip) into a vein.
Dosage
The dose of the medicine depends on the type of infection, the patient's age, and whether there are kidney problems.
Adults and adolescents over 12 years of age
The usual dose is 4 g + 0.5 g of piperacillin with tazobactam, given every 6 to 8 hours into a vein (directly into the bloodstream).
Children aged 2 to 12 years
In children with abdominal infections, the usual dose is 100 mg + 12.5 mg of piperacillin with tazobactam per kg of body weight, given every 8 hours into a vein (directly into the bloodstream). In children with low white blood cell counts, the usual dose is 80 mg + 10 mg of piperacillin with tazobactam per kg of body weight given every 6 hours into a vein.
The doctor will calculate the dose of Piperacillin/Tazobactam Sandoz 4 g/0.5 g based on the child's body weight, but no single dose will exceed 4 g + 0.5 g.
The medicine is administered until the symptoms of infection have completely resolved (for 5 to 14 days).
Patients with impaired kidney function
The doctor may reduce the dose or frequency of administration of Piperacillin/Tazobactam Sandoz 4 g/0.5 g. The doctor may also recommend regular blood tests to ensure the dose is appropriate, especially if the medicine needs to be used for a prolonged period.
Administration of a higher than recommended dose of Piperacillin/Tazobactam Sandoz 4 g/0.5 g
Since Piperacillin/Tazobactam Sandoz 4 g/0.5 g is 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 suspects that an overdose has occurred, the doctor should be informed immediately.
Missed dose of Piperacillin/Tazobactam Sandoz 4 g/0.5 g
If the patient suspects that a dose of Piperacillin/Tazobactam Sandoz 4 g/0.5 g has been missed, they should inform the doctor or other healthcare professional immediately.
If there are any further doubts about the use of this medicine, consult the doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If any of the following potentially serious side effects occur in the patient,
seek immediate medical advice:
Serious side effects of Piperacillin/Tazobactam Sandoz 4 g/0.5 g (frequencies are given in
parentheses):
severe skin rashes [Stevens-Johnson syndrome, bullous dermatitis (frequency unknown), exfoliative dermatitis (frequency unknown), toxic epidermal necrolysis (rare)], initially appearing on the trunk as red, target-shaped or circular lesions, often with blisters in the central area. Additional symptoms include: ulceration 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 become life-threatening.
severe allergic reaction, which may lead to death (drug reaction with eosinophilia and systemic symptoms) and may involve the skin and, importantly, other organs such as the kidneys and liver (frequency unknown)
fever with skin disorder (acute generalized exanthematous pustulosis), in which numerous small fluid-filled blisters appear on large areas of swollen and reddened skin (frequency unknown)
swelling of the face, lips, tongue or other parts of the body (frequency unknown)
shortness of breath, wheezing or difficulty breathing (frequency unknown)
severe rash or urticaria (not very common), itching or rash on the skin (common)
yellowing of the eyes or skin (frequency unknown)
blood cell damage [symptoms include: unexpected shortness of breath, red or brown discoloration of urine (frequency unknown), nosebleeds (rare), and appearance of small bruises (frequency unknown)], significant decrease in white blood cell count (rare)
severe or persistent diarrhoea, accompanied by 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 or healthcare professional.
Very common side effects (may affect more than 1 in 10 people):
diarrhoea
Common side effects (may affect less than 1 in 10 people):
fungal infection
decreased platelet count, decreased red blood cell count or decreased concentration of blood pigment (haemoglobin), abnormal laboratory test result (positive direct Coombs test), prolonged blood clotting time (prolonged partial thromboplastin time)
decreased protein concentration in blood
headache, insomnia
abdominal pain, vomiting, nausea, constipation, indigestion
increased liver enzyme activity
skin rash, itching
abnormal kidney function test results
fever, injection site reaction
Uncommon side effects (may affect less than 1 in 100 people):
decreased white blood cell count (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
decreased potassium concentration in blood, decreased blood glucose concentration
seizure attacks observed in patients receiving high doses of the medicine or in patients with kidney problems
low blood pressure, phlebitis (felt as pain or redness in the inflamed area)
skin redness
increased concentration of breakdown product of blood pigment (bilirubin)
skin reactions with redness, skin lesions, urticaria
joint and muscle pain
chills
Rare side effects (may affect less than 1 in 1000 people):
marked decrease in white blood cells (agranulocytosis), nosebleeds
severe infection of the large intestine, inflammation of the mucous membrane of the mouth
detachment of the outer layer of skin over the entire body [toxic epidermal necrolysis (Lyell's syndrome)]
Side effects with unknown frequency (frequency cannot be determined from available data):
marked decrease in red blood cells, white blood cells and platelets (pancytopenia), decreased white blood cell count (neutropenia), decreased red blood cell count due to their premature breakdown or degradation, minor bruising, prolonged bleeding time, increased platelet count, increased number of a certain type of white blood cells (eosinophilia)
allergic reaction, including severe
hepatitis, yellow discoloration of the skin or whites of the eyes
severe systemic allergic reaction with skin rash and mucous membranes, blisters and other skin lesions (Stevens-Johnson syndrome), severe allergic reaction involving the skin and other organs such as kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters located on swollen and reddened large areas of skin with fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
weakness and kidney function disorders
lung disease characterised by increased number of eosinophils (a type of white blood cells) in the lungs
acute disorientation and confusion (delirium)
Fever and rash occurred more frequently in patients with cystic fibrosis receiving piperacillin.
Beta-lactam antibiotics, including piperacillin with tazobactam, may lead to symptoms of brain dysfunction (encephalopathy) and seizures.
Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Side effects can 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, 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 authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Piperacillin/Tazobactam Sandoz 4 g/0.5 g

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "EXP". The expiry date refers to the last day of the specified month.
Unopened vials/bottles:
No special storage conditions required.
Storage conditions for reconstituted and diluted medicinal product: see information at the end of the leaflet entitled "Information intended exclusively for healthcare professionals".
This medicine is for single use only. Any unused solution should be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Piperacillin/Tazobactam Sandoz 4 g/0.5 g contains
The active substances are piperacillin and tazobactam.
Each vial or bottle of Piperacillin/Tazobactam Sandoz 4 g/0.5 g contains 4 g of piperacillin
(as sodium piperacillin) and 0.5 g of tazobactam (as sodium tazobactam).
The medicine contains no other ingredients besides the active substances.

What Piperacillin/Tazobactam Sandoz 4 g/0.5 g looks like and contents of the pack
Piperacillin/Tazobactam Sandoz 4 g/0.5 g is a white or almost white powder for solution for infusion in glass vials or bottles. The vials and bottles are packed in cardboard boxes.
Pack sizes: 1, 5, 10, 12 and 50 vials or bottles.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer/Importer
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

For further information about the medicine and its names in the Member States of the European Economic Area, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Information intended exclusively for medical professionals

Warning: The use of this medicinal product is not recommended in adult patients for the treatment of bacteremia caused by E. coli and K. pneumoniae strains (ceftriaxone-resistant) producing extended-spectrum β-lactamases (ESBL).

After reconstitution and dilution:
Chemical and physical stability has been demonstrated for 24 hours at 20–25°C and for 48 hours at 2–8°C.
From a microbiological point of view, the product should be used immediately after opening.
Otherwise, the user is responsible for the storage time and conditions.
The solution should not be stored for longer than 24 hours at a temperature of 2°C to 8°C unless reconstitution/dilution was carried out under controlled aseptic conditions.

Instructions for use
Piperacillin/Tazobactam Sandoz 4 g/0.5 g is administered by intravenous infusion (over 30 minutes).
The medicinal product must be reconstituted and diluted under aseptic conditions. Before administration, inspect the solution visually for particulate matter and discoloration. The solution should only be administered if it is clear and free of solid particles.

Intravenous administration
The contents of each vial/bottle should be reconstituted with the volume of one of the compatible diluents specified in the table below. Mix gently by swirling until dissolved, which usually occurs within 3 minutes of continuous mixing (detailed handling instructions are provided below).

| Vial/bottle content | Diluent volume* | |--------------------------|----------------------| | 4 g piperacillin + 0.5 g tazobactam | 20 ml |

* Compatible diluents:

• Sterile water for injection,
• 9 mg/ml (0.9%) sodium chloride solution in water for injection,
• 50 mg/ml (5%) glucose solution in water for injection,
• 50 mg/ml (5%) glucose solution in 9 mg/ml (0.9%) sodium chloride solution.

The reconstituted solution should be withdrawn with a syringe from the vial or bottle. After reconstitution according to the recommended procedure, the solution withdrawn from the vial or bottle will contain the labeled amount of piperacillin and tazobactam.

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

• 9 mg/ml (0.9%) sodium chloride solution in water for injection,
• 50 mg/ml (5%) glucose solution in water for injection,
• 60 mg/ml (6%) dextran 40 solution in 9 mg/ml (0.9%) sodium chloride solution.

Incompatibilities
If Piperacillin/Tazobactam Sandoz 4 g/0.5 g is to be administered simultaneously with another antibiotic (e.g., an aminoglycoside), these products should be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside. However, it has been demonstrated that amikacin and gentamicin are compatible in vitro with Piperacillin/Tazobactam Sandoz 4 g/0.5 g in certain diluents and at specific concentrations (see below: Administration of Piperacillin/Tazobactam Sandoz 4 g/0.5 g with aminoglycosides).

Piperacillin with tazobactam should not be mixed with other substances in the same syringe or infusion container, as compatibility has not been established.
Piperacillin with tazobactam should be administered through a separate infusion set. The exception includes medicinal products whose compatibility has been confirmed.

Due to chemical instability, piperacillin with tazobactam should not be used in solutions containing sodium bicarbonate only.

Lactated Ringer's solution (Hartmann's solution) is incompatible with combination products containing piperacillin with tazobactam.

Combination products containing piperacillin with tazobactam should not be added to blood products or albumin hydrolysates.

Administration of Piperacillin/Tazobactam Sandoz 4 g/0.5 g with aminoglycosides
Mixing beta-lactam antibiotics with aminoglycosides in vitro may lead to significant inactivation of aminoglycosides. Therefore, it is recommended that Piperacillin/Tazobactam Sandoz 4 g/0.5 g and aminoglycosides be administered separately. If simultaneous administration of an aminoglycoside and Piperacillin/Tazobactam Sandoz 4 g/0.5 g is necessary, they should be reconstituted and diluted separately. If simultaneous administration is required, Piperacillin/Tazobactam Sandoz 4 g/0.5 g is compatible and may be administered simultaneously through a common Y-site infusion line only with the aminoglycosides listed below and under the conditions described below.

* The dose of aminoglycoside should be adjusted according to the patient's body weight, severity of infection (severe or life-threatening), and renal function (creatinine clearance).
Compatibility of piperacillin with tazobactam with other aminoglycosides has not been established. Only the above-mentioned concentrations and solvents of amikacin and gentamicin with the specified doses of piperacillin with tazobactam have been determined as compatible for simultaneous administration via a common Y-site infusion line. Simultaneous administration via a common Y-site infusion line in any manner other than that described above may result in inactivation of the aminoglycoside by piperacillin with tazobactam.