Piperacillin/tazobactam kabi 4 g + 0.5 g

Package leaflet: Information for the user

Piperacillin/Tazobactam Kabi 2 g + 0,25 g, powder for solution for infusion
Piperacillin/Tazobactam Kabi 4 g + 0,5 g, 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, ask your doctor or nurse.
­ If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.
Contents of the leaflet

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

1. What Piperacillin/Tazobactam Kabi is and what it is 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 resistant to piperacillin from surviving. This means that more strains of bacteria will be killed when piperacillin and tazobactam are given together.
Piperacillin/Tazobactam Kabi is used in adult patients and adolescents for the treatment of bacterial infections of the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdominal cavity, skin and blood. Piperacillin/Tazobactam Kabi may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin/Tazobactam Kabi is used in children aged 2 to 12 years for the treatment of intra-abdominal infections, including appendicitis, peritonitis (infection of the fluid and membrane lining the abdominal organs), and cholecystitis (infection of the gallbladder).
Piperacillin/Tazobactam Kabi 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 administering Piperacillin/Tazobactam Kabi together with other antibiotics.

2. Important information before using Piperacillin/Tazobactam Kabi

When not to use Piperacillin/Tazobactam Kabi

• 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 has allergies to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin/Tazobactam Kabi.

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

• If the patient has any allergies. If the patient has multiple allergies, they should ensure they have informed the doctor or healthcare professional before receiving the medicine.
• If the patient has diarrhoea before treatment, or if diarrhoea occurs during or after treatment. The doctor or healthcare professional should be informed immediately. Do not take any anti-diarrhoeal medicines without consulting a doctor.
• If the patient has low blood potassium levels. The doctor may check kidney function before treatment and perform regular blood tests during treatment.
• If the patient has kidney or liver problems, or is undergoing haemodialysis. The doctor may check kidney function before treatment and perform regular blood tests during treatment.
• If the patient is taking medicines to prevent excessive blood clotting, known as anticoagulants (see also Piperacillin/Tazobactam Kabi with other medicines in this leaflet), or if unexpected bleeding occurs during treatment. In such cases, inform the doctor or healthcare professional immediately.
• If the patient is receiving the antibiotic vancomycin at the same time as Piperacillin/Tazobactam Kabi, as this may increase the risk of kidney damage (see also Piperacillin/Tazobactam Kabi with other medicines in this leaflet).
• If the patient experiences seizures during treatment. Inform the doctor or healthcare professional immediately.
• If the patient suspects a new infection has occurred or an existing infection has worsened. Inform the doctor or healthcare professional.
• If the patient develops severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), or acute generalised exanthematous pustulosis (AGEP). Treatment with Piperacillin/Tazobactam Kabi should be stopped and medical advice sought immediately if any of the symptoms listed in section 4 occur.

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 inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition may 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.
If symptoms of an allergic reaction occur together with chest pain, contact a doctor immediately. This may be a sign of Kounis syndrome.
If unexplained muscle pain, tenderness or weakness and/or dark urine occur, contact a doctor immediately. This may be a sign of muscle breakdown (called rhabdomyolysis), which can lead to kidney problems.

Children under 2 years of age
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 Kabi with other medicines
Inform the doctor or pharmacist about all medicines currently taken, recently taken, or planned for use. Some medicines may interact with piperacillin and tazobactam.
These include:

• A medicine used to treat gout (probenecid); it 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, acetylsalicylic acid);
• Medicines used to relax muscles during surgery; if the patient is to undergo general anaesthesia, they should inform the doctor about taking this medicine;
• Methotrexate (a medicine used in cancer, joint inflammation, 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 cancer medicines);
• Medicines containing other antibiotics: tobramycin, gentamicin, or vancomycin; if the patient has kidney problems, they should inform the doctor. Concurrent use of Piperacillin/Tazobactam Kabi and vancomycin may increase the risk of kidney damage, even if the patient does not have existing kidney problems.

Effect on laboratory test results
If the patient is to provide a blood or urine sample, they should inform the doctor or healthcare professional that they are receiving Piperacillin/Tazobactam Kabi.

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

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

Piperacillin/Tazobactam Kabi 2 g + 0.25 g contains 112 mg of sodium (the main component of table salt) in each vial. This corresponds to 5.6% of the maximum recommended daily dietary sodium intake for adults.
Piperacillin/Tazobactam Kabi 4 g + 0.5 g contains 224 mg of sodium (the main component of table salt) in each vial. This corresponds to 11.2% of the maximum recommended daily dietary sodium intake for adults.
This should be taken into account in patients who are monitoring their dietary sodium intake.

3. How to use Piperacillin/Tazobactam Kabi

The medicine will be administered by a doctor or another healthcare professional as an 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 the patient may have.

Adult patients and adolescents aged 12 years or older
The recommended dose is 4 g of piperacillin and 0.5 g of tazobactam administered intravenously (directly into the blood), every 6 to 8 hours.

Children aged 2 to 12 years
For children with abdominal infections, the recommended dose is 100 mg of piperacillin and 12.5 mg of tazobactam per kg of body weight, administered intravenously (directly into the blood), every 8 hours. The usual dose for children with low white blood cell counts is 80 mg of piperacillin and 10 mg of tazobactam per kg of body weight, administered 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 Kabi will not exceed 4 g + 0.5 g.

The patient will receive Piperacillin/Tazobactam Kabi until all signs of infection have completely resolved (for 5 to 14 days).

Patients with kidney disease
The doctor may recommend reducing the dose of Piperacillin/Tazobactam Kabi 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.

Administration of a higher than recommended dose of Piperacillin/Tazobactam Kabi
Piperacillin/Tazobactam Kabi will be administered by a doctor or another healthcare professional; therefore, incorrect dosing 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 Kabi
If the patient thinks a dose of Piperacillin/Tazobactam Kabi has been missed, they should inform the doctor or another healthcare professional immediately.

If there are any further doubts regarding 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 everybody will get them.
If any of the potentially serious side effects of Piperacillin/Tazobactam Kabi occur, you should immediately consult a doctor.

Serious side effects (with frequency stated in parentheses) of piperacillin with tazobactam include:

• severe skin reactions, initially appearing as red spots resembling targets or circular patches, often with centrally located blisters, occurring on the trunk; additionally, ulceration of the mouth, throat, nose, limbs, genital organs, and redness and swelling of the eyes (conjunctivitis) may occur; the rash may progress to extensive blistering or peeling of the skin and may be life-threatening; these may be symptoms of Stevens-Johnson syndrome (frequency not known), bullous dermatitis (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare);
• skin disease accompanied by fever, manifesting as numerous small fluid-filled blisters on a swollen and red large skin surface, known as acute generalized exanthematous pustulosis (frequency not known);
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms), which may affect the skin and, more importantly, other organs beneath the skin, such as kidneys and liver (frequency not known);
• swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing (allergic reactions, including anaphylactic shock, frequency not known);
• sudden chest pain associated with an allergic reaction known as Kounis syndrome (frequency not known);
• severe rash or hives (not common), itching or skin rash (common);
• hepatitis (frequency not known), yellowing of the skin or whites of the eyes (jaundice, frequency not known);
• low level of red blood cells (anaemia, common), excessive breakdown of red blood cells leading to unexpected breathlessness, red or brown discoloration of urine (haemolytic anaemia, frequency not known);
• low level of platelets, which may lead to bleeding and bruising (thrombocytopenia, common);
• low level of white blood cells that fight infection (leukopenia, not common or neutropenia, frequency not known);
• very low level of white blood cells called granulocytes (agranulocytosis, rare);
• high level of platelets (thrombocytosis, frequency not known);
• high level of white blood cells called eosinophils (eosinophilia, frequency not known);
• low level of all types of blood cells, including platelets (pancytopenia, frequency not known);
• severe or persistent diarrhoea with fever or weakness (pseudomembranous colitis, rare);
• decreased potassium levels in the blood (not common);
• seizures, observed in patients receiving high doses of the medicine or in those with kidney problems (not common);
• severe muscle pain, tenderness or weakness (rhabdomyolysis, frequency not known).

If any of the side effects worsen or if any side effects not listed in this leaflet occur, inform your doctor or other healthcare professional immediately.

Very common side effects (may occur in more than 1 in 10 patients):

• diarrhoea.

Common side effects (may occur in less than 1 in 10 patients):

• fungal infections (e.g. candidiasis);
• antibodies in the blood that attack red blood cells (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time), decreased amount of protein in the blood;
• headache, insomnia;
• abdominal pain, vomiting, nausea, constipation, gastrointestinal discomfort;
• increased liver enzyme activity in the blood;
• abnormal blood test results indicating kidney function;
• fever, injection site reaction.

Uncommon side effects (may occur in less than 1 in 100 patients):

• prolonged blood clotting time (prolonged prothrombin time), decreased blood sugar levels;
• low blood pressure, phlebitis (feeling of excessive sensitivity to touch or redness in the inflamed area), skin redness;
• increased levels of a breakdown product of blood pigment (bilirubin);
• skin reactions including redness, skin lesions;
• joint and muscle pain;
• chills.

Rare side effects (may occur in less than 1 in 1000 patients):

• nosebleeds, inflammation of the mucous membrane of the mouth (stomatitis).

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

• minor bruising, prolonged bleeding time;
• blistering disease in which blisters form on the skin and mucous membranes (linear IgA disease);
• impaired kidney function and kidney-related problems;
• lung disease in which eosinophils (a type of white blood cells) increasingly accumulate in the lungs;
• acute disorientation and confusion (delirium).

Fever and rash have occurred more frequently in patients with cystic fibrosis receiving piperacillin.
Beta-lactam antibiotics, including piperacillin with tazobactam, may cause symptoms of encephalopathy and seizures.

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor 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
Phone: +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.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Piperacillin/Tazobactam Kabi

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vials after "EXP". The expiry date refers to the last day of the specified month.
Unopened vials
Do not store above 25°C. Store vials in the outer packaging.
For single use only. Any unused solution should be discarded.
Medicines must not be disposed of via the sewage system 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 Package and Other Information

What Piperacillin/Tazobactam Kabi Contains

• The active substances in this medicine are piperacillin and tazobactam.
  Piperacillin/Tazobactam Kabi 2 g + 0,25 g: Each vial contains 2 g of piperacillin as the sodium salt and 0.25 g of tazobactam as the sodium salt.
  Piperacillin/Tazobactam Kabi 4 g + 0,5 g: Each vial contains 4 g of piperacillin as the sodium salt and 0.5 g of tazobactam as the sodium salt.

This medicine contains no other ingredients.

What Piperacillin/Tazobactam Kabi Looks Like and Contents of the Pack

Piperacillin/Tazobactam Kabi is a white or almost white lyophilized powder for the preparation of an infusion solution.

Piperacillin/Tazobactam Kabi 2 g + 0,25 g is available in 15 ml and 50 ml vials made of colourless glass (Type II), with a halobutyl rubber stopper and an aluminium flip-off cap, packed in a cardboard box.

Piperacillin/Tazobactam Kabi 4 g + 0,5 g is available in 50 ml vials made of colourless glass (Type II), with a halobutyl rubber stopper and an aluminium flip-off cap, packed in a cardboard box.

Pack sizes contain 1, 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder

Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Poland

Manufacturer

LABESFAL - Laboratorios Almiro S.A.
FRESENIUS KABI GROUP
3465-157 Santiago de Besteiros
Portugal
Applies to Piperacillin/Tazobactam Kabi 4 g + 0,5 g

MITIM S.r.l.
Via Cacciamali n°34-36-38
25125 Brescia
Italy

For further information, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Phone: +48 22 345 67 89

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Austria
Piperacillin/Tazobactam Kabi 4 g/0.5 g Powder for solution for infusion

Belgium
Piperacilline/Tazobactam Fresenius Kabi N.V. 2 g/0.25 g powder for solution for infusion/poudre pour solution pour perfusion/Pulver zur Herstellung einer Infusionslösung
Piperacilline/Tazobactam Fresenius Kabi N.V. 4 g/0.5 g powder for solution for infusion/poudre pour solution pour perfusion/Pulver zur Herstellung einer Infusionslösung

Bulgaria
Пиперацилин/Тазобактам Каби 2 g/0.25 g прах за инфузионен разтвор
Пиперацилин/Тазобактам Каби 4 g/0.5 g прах за инфузионен разтвор

Cyprus
Piperacillin/Tazobactam Kabi 2 g/0.25 g, Κόνις για διάλυμα προς έγχυση
Piperacillin/Tazobactam Kabi 4 g/0.5 g, Κόνις για διάλυμα προς έγχυση

Czech Republic
Piperacillin/Tazobactam Kabi 4 g/0.5 g

Denmark
Piperacillin/Tazobactam Fresenius Kabi 2 g/0.25 g Powder for solution for infusion, solution
Piperacillin/Tazobactam Fresenius Kabi 4 g/0.5 g Powder for solution for infusion, solution

Estonia
Piperacillin/Tazobactam Fresenius Kabi

Finland
Piperacillin/Tazobactam Fresenius Kabi 2 g/0.25 g infuusiokuiva-aine, liuosta varten
Piperacillin/Tazobactam Fresenius Kabi 4 g/0.5 g infuusiokuiva-aine, liuosta varten

France
Piperacilline/Tazobactam Kabi 2 g/0.25 g, poudre pour solution pour perfusion
Piperacilline/Tazobactam Kabi 4 g/0.5 g, poudre pour solution pour perfusion

Greece
Piperacillin/Tazobactam Kabi 2 g/0.25 g, Κόνις για διάλυμα προς έγχυση
Piperacillin/Tazobactam Kabi 4 g/0.5 g, Κόνις για διάλυμα προς έγχυση

Spain
Piperacillin/Tazobactam Kabi 2 g/0.25 g Polvo para solución para perfusión
Piperacillin/Tazobactam Kabi 4 g/0.5 g Polvo para solución para perfusión

Netherlands
Piperacilline/Tazobactam Fresenius Kabi 2 g/0.25 g poeder voor oplossing voor infusie

Ireland
Piperacilline/Tazobactam Fresenius Kabi 4 g/0.5 g poeder voor oplossing voor infusie
Piperacillin/Tazobactam 2 g/0.25 g powder for solution for infusion
Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion

Germany
Piperacillin/Tazobacatm Kabi 2 g/0.25 g Pulver zur Herstellung einer Infusionslösung
Piperacillin/Tazobacatm Kabi 4 g/0.5 g Pulver zur Herstellung einer Infusionslösung

Norway
Piperacillin/Tazobactam Fresenius Kabi 2 g/0.25 g pulver til infusjonsvæske, oppløsning
Piperacillin/Tazobactam Fresenius Kabi 4 g/0.5 g pulver til infusjonsvæske, oppløsning

Poland
Piperacillin/Tazobactam Kabi 2 g + 0,25 g, proszek do sporządzania roztworu do infuzji
Piperacillin/Tazobactam Kabi 4 g + 0,5 g, proszek do sporządzania roztworu do infuzji

Portugal
Piperacilina/Tazobactam Kabi 2 g/0.25 g
Piperacilina/Tazobactam Kabi 4 g/0.5 g

Romania
Piperacillin/Tazobactam Kabi 2 g/0.25 g, pulbere pentru soluţie perfuzabilă
Piperacillin/Tazobactam Kabi 4 g/0.5 g, pulbere pentru soluţie perfuzabilă

Slovakia
Piperacillin/Tazobactam Kabi 2 g/0.25 g
Piperacillin/Tazobactam Kabi 4 g/0.5 g

Slovenia
Piperacilin/tazobaktam Kabi 2 g/0.25 g prašek za raztopino za infundiranje
Piperacilin/tazobaktam Kabi 4 g/0.5 g prašek za raztopino za infundiranje

Sweden
Piperacillin/Tazobactam Fresenius Kabi 2 g/0.25 g Powder for solution for infusion
Piperacillin/Tazobactam Fresenius Kabi 4 g/0.5 g Powder for solution for infusion

Hungary
Piperacillin/Tazobactam Kabi 4 g/0.5 g por oldatos infúzióhoz

United Kingdom
Piperacillin/Tazobactam 2 g/0.25 g powder for solution for infusion
Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion

Information intended exclusively for medical professionals:

The following information is an extract from the Summary of Product Characteristics, prepared
to provide guidance on the administration of Piperacillin/Tazobactam Kabi. The physician
should review the Summary of Product Characteristics before administering this medicinal product
to any patient.
Pharmaceutical incompatibilities with solvents and other medicinal products
RINGER’S ACETATE SOLUTION (HARTMANN’S SOLUTION) IS PHARMACEUTICALLY INCOMPATIBLE
WITH PIPERACILLIN/TAZOBACTAM KABI.
IF PIPERACILLIN/TAZOBACTAM KABI IS ADMINISTERED CONCURRENTLY WITH OTHER
ANTIBIOTICS (E.G. AMINOGLYCOSIDES), THESE MEDICINAL PRODUCTS MUST BE GIVEN
SEPARATELY. MIXING PIPERACILLIN/TAZOBACTAM KABI IN VITRO WITH AN AMINOGLYCOSIDE
MAY RESULT IN SIGNIFICANT INACTIVATION OF THE AMINOGLYCOSIDE.
DO NOT MIX PIPERACILLIN/TAZOBACTAM KABI WITH OTHER MEDICINAL PRODUCTS
IN A SYRINGE OR INFUSION BAG, AS COMPATIBILITY HAS NOT BEEN ESTABLISHED.
DUE TO CHEMICAL INSTABILITY, PIPERACILLIN/TAZOBACTAM KABI SHOULD NOT BE USED
WITH SOLUTIONS CONTAINING SODIUM BICARBONATE.
PIPERSACILLIN/TAZOBACTAM KABI MUST NOT BE ADDED TO BLOOD PRODUCTS OR ALBUMIN
HYDROLYSATES.
Instructions for use
Piperacillin/Tazobactam Kabi should be administered by intravenous infusion (over 30 minutes).
Intravenous administration
Prepare the solution by adding the appropriate volume of one of the solvents listed below to the vial.
Shake the vial until the powder is completely dissolved. The powder dissolves within 5 to 10 minutes of continuous shaking (further details on handling the medicinal product are provided below).
Volume of solvent added to the vial
Vial content
Solvent*
2 g + 0.25 g (2 g piperacillin and 0.25 g tazobactam) 10 ml
4 g + 0.5 g (4 g piperacillin and 0.5 g tazobactam) 20 ml
* Compatible solvents for reconstitution:

• 0.9% (9 mg/ml) sodium chloride solution for injection;
• sterile water for injection. The maximum recommended volume of sterile water for injection is 50 ml per dose.

The reconstituted solution should be withdrawn from the vial using a syringe. After reconstitution according to the instructions, 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 diluents:

• 0.9% (9 mg/ml) sodium chloride solution for injection;
• 5% glucose solution;
• 6% dextran solution in 0.9% sodium chloride solution.