Piperacillin + Tazobactam Kalceks

Leaflet accompanying the packaging: information for the user

Piperacillin + Tazobactam Kalceks, 2 g + 0.25 g, powder for solution for infusion

Piperacillin + Tazobactam Kalceks, 4 g + 0.5 g, powder for solution for infusion

Piperacillin + Tazobactam

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

• Keep this leaflet, you may need to read it again.
• 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 Kalceks and what is it used for
• 2. Important information before using Piperacillin + Tazobactam Kalceks
• 3. How to use Piperacillin + Tazobactam Kalceks
• 4. Possible side effects
• 5. How to store Piperacillin + Tazobactam Kalceks
• 6. Contents of the packaging and other information

1. What is Piperacillin + Tazobactam Kalceks and what is it used for

Piperacillin + Tazobactam Kalceks contains the active substances piperacillin and tazobactam.
Piperacillin belongs to a group of medicines called broad-spectrum penicillins. It is an antibiotic that can kill many types of bacteria. Tazobactam can prevent some bacteria that are resistant to piperacillin from surviving. This means that if piperacillin is given together with tazobactam, more types of bacteria will be killed.
The medicine is used:

• in adults and adolescentsto treat bacterial infections, such as lower respiratory tract infections (lungs), urinary tract infections (kidneys and bladder), abdominal cavity, skin, or blood infections. This medicine may be used to treat bacterial infections in patients with a low white blood cell count (with reduced resistance to infections).
• in children aged 2 to 12 yearsto treat abdominal cavity infections, such as appendicitis, peritonitis (infection of the fluid and mucous membrane of the abdominal organs), and biliary tract infections (bile ducts). The medicine may be used to treat bacterial infections in patients with a low white blood cell count (with reduced resistance to infections).

In some severe infections, the attending physician may decide to use piperacillin with tazobactam in combination with other antibiotics.

2. Important information before using Piperacillin + Tazobactam Kalceks

When not to use Piperacillin + Tazobactam Kalceks:

• if the patient is allergic to piperacillin or tazobactam;
• if the patient is allergic to antibiotics called penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may be allergic to Piperacillin + Tazobactam Kalceks.

Warnings and precautions

Before starting to use Piperacillin + Tazobactam Kalceks, the patient should discuss it with their doctor, pharmacist, or nurse:

• if the patient has allergies;
• if the patient has had diarrhea in the past;
• if the patient has low potassium levels in the blood. The attending physician may recommend a kidney test before starting treatment and regular blood tests during treatment;
• if the patient has kidney, liver, or is undergoing hemodialysis. The doctor may recommend a kidney test before starting treatment and regular blood tests during treatment;
• if the patient is taking another antibiotic called vancomycin during treatment, as the risk of kidney damage may increase (see also "Piperacillin + Tazobactam Kalceks and other medicines" in this leaflet);
• if the patient is taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also "Piperacillin + Tazobactam Kalceks and other medicines" in this leaflet).

The patient should immediatelyinform their doctor or nurse:

• if they experience diarrhea during or after treatment. They should not take anti-diarrheal medicines without consulting their doctor;
• if they experience unexpected bleeding during treatment;
• if they experience seizures during treatment;
• if they think they have developed a new or worsening infection.

Hemophagocytic lymphohistiocytosis
There have been reports of a condition in which the immune system produces too many normally harmless white blood cells called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This condition can be life-threatening if not diagnosed and treated early. If the patient experiences multiple symptoms such as fever, swollen lymph nodes, weakness, dizziness, shortness of breath, bluish discoloration, or skin rash, they should contact their doctor immediately.

Children

The medicine should not be used in children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin + Tazobactam Kalceks and other medicines

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

• medicines that lower potassium levels in the blood (e.g., diuretic tablets or certain anticancer medicines);
• muscle relaxants used during surgery. The patient should inform their doctor about taking the medicine if they are to undergo general anesthesia;
• medicines used to reduce blood clotting or treat blood clots (e.g., heparin, warfarin, or aspirin);
• methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may prolong the elimination of methotrexate from the body;
• a medicine used to treat gout (probenecid). It may prolong the elimination of piperacillin and tazobactam from the body.
• medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin. The patient should inform their doctor about kidney problems. Using piperacillin with tazobactam and vancomycin at the same time may increase the risk of kidney damage even in patients without kidney disease.

Effect on laboratory test results
The patient should inform their doctor or laboratory staff about taking this medicine if they are to have a blood or urine test.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
Piperacillin and tazobactam may pass into the baby's body through the placenta or breast milk.
The doctor will decide whether the medicine is suitable for a pregnant or breastfeeding woman.

Driving and using machines

Taking this medicine should not affect the patient's ability to drive or operate machines.

Piperacillin + Tazobactam Kalceks contains sodium

Piperacillin + Tazobactam Kalceks, 2 g + 0.25 g
The medicine contains 108 mg of sodium (the main component of common salt) per vial. This is equivalent to 5.4% of the maximum recommended daily intake of sodium in an adult's diet.
Piperacillin + Tazobactam Kalceks, 4 g + 0.5 g
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 an adult's diet.

3. How to use Piperacillin + Tazobactam Kalceks

The medicine is given by a doctor or nurse in the form of an infusion (a drip lasting 30 minutes) into one of the veins.

Dosage

The dose of the medicine depends on the type of disease, the patient's age, and the presence of kidney problems.

Adults and adolescents over 12 years of age

The usual dose is 4 g of piperacillin and 0.5 g of tazobactam given every 6-8 hours intravenously (directly into the bloodstream).

Children aged 2 to 12 years

The usual dose for children with abdominal cavity infections is 100 mg of piperacillin and 12.5 mg of tazobactam per kilogram of body weight given intravenously every 8 hours. The usual dose for children with a low white blood cell count is 80 mg of piperacillin and 10 mg of tazobactam per kilogram of body weight given intravenously every 6 hours.
The attending physician calculates the dose of the medicine based on the child's body weight, assuming that the individual dose of the medicine is not greater than 4 g of piperacillin and 0.5 g of tazobactam.
The medicine is used until the infection symptoms completely disappear (for 5 to 14 days).

Patients with kidney problems

The attending physician may reduce the dose of the medicine or the frequency of its administration. The doctor may also recommend a blood test to ensure that the used dose of the medicine is appropriate, especially if the medicine needs to be used for a long time.

Using a higher than recommended dose of Piperacillin + Tazobactam Kalceks

The medicine is given by a doctor or nurse, so using an incorrect dose of the medicine is unlikely. However, if the patient experiences side effects, such as seizures, or thinks they have received too much medicine, they should immediately inform their doctor.

Missing a dose of Piperacillin + Tazobactam Kalceks

If the patient thinks they have missed a dose of the medicine, they should immediately inform their doctor or nurse.
In case of any further doubts about using this medicine, the patient should consult their doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The patient should immediatelyinform their doctor or nurse if they notice any of the following serious side effects :

• severe skin reactions (Stevens-Johnson syndrome, bullous dermatitis, exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)) initially appearing as reddened or round patches, often with centrally located blisters, occurring on the torso. Additional symptoms include: oral, throat, nose, limb, genital, or conjunctival ulcers (red and swollen eyes). The rash may develop into widespread blisters or skin peeling and potentially be life-threatening;
• a serious, potentially life-threatening allergic reaction (called "drug reaction with eosinophilia and systemic symptoms" (frequency not known)), which may involve the skin, and more importantly, other organs under the skin, such as the kidneys and liver;
• a skin disease (called "acute generalized exanthematous pustulosis" (frequency not known)) with accompanying fever; characterized by numerous small blisters filled with fluid, located on a swollen and reddened large skin 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 (uncommon);
• yellowing of the whites of the eyes or skin (frequency not known);
• blood cell damage (symptoms are: unexpected shortness of breath, red or brown urine, small bruises (frequency not known)), significant decrease in white blood cell count (rare);
• severe or persistent diarrhea with fever or weakness (rare). If any of the side effects get worse or if the patient experiences any side effects not listed in this leaflet, they should tell their doctor or another healthcare professional.

Other side effects

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

• diarrhea

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• decreased white blood cell count (leukopenia)
• decreased potassium levels in the blood
• seizures (convulsions), observed in patients taking high doses of the medicine or having kidney problems
• low blood pressure, vein inflammation (felt as tenderness or redness at the injection site), skin redness
• skin reactions with redness, skin changes, hives
• joint and muscle pain
• chills
• decreased blood sugar levels, increased bilirubin levels in the blood, prolonged blood clotting time (prolonged prothrombin time)

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

• nosebleeds
• mouth ulcers

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

• significant decrease in red blood cell, white blood cell, and platelet counts (pancytopenia), decreased white blood cell count (neutropenia), decreased red blood cell count due to their premature breakdown or degradation, increased platelet count, increased count of a certain type of white blood cells (eosinophilia)
• allergic reactions
• acute confusion and disorientation (delirium)
• a lung disease in which eosinophils (a type of white blood cell) appear in the lungs in increased numbers
• liver inflammation, yellowing of the skin or whites of the eyes
• small pinpoint bruises
• kidney function impairment and kidney disease
• changes in blood tests (e.g., prolonged bleeding time, increased gamma-glutamyltransferase activity)

Treatment with piperacillin is associated with an increased frequency of fever and rash in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin with tazobactam, may lead to the development of symptoms of brain function disorders (encephalopathy) or epileptic seizures (convulsions).

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 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 will help to gather more information on the safety of the medicine.

5. How to store Piperacillin + Tazobactam Kalceks

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial label after "EXP". The expiry date refers to the last day of the month.
Do not store above 30°C.
Store the vial in the outer packaging to protect it from light.
Shelf life after reconstitution in the vial
After reconstitution with the recommended solvent, the chemical and physical stability of the medicine has been demonstrated for 12 hours at 25°C and 48 hours at 2-8°C.
Shelf life after dilution of the reconstituted solution
The chemical and physical stability of the reconstituted solution has been demonstrated for 12 hours at 25°C and 48 hours at 2-8°C, after dilution with Ringer's solution, 9 mg/mL (0.9%) sodium chloride, 50 mg/mL (5%) glucose, or 50 mg/mL (5%) glucose in 9 mg/mL (0.9%) sodium chloride, as recommended for further dilution.
To obtain information on compatible solutions and volumes of solutions used for reconstitution and dilution, see "Information intended for healthcare professionals only" below.
From a microbiological point of view, the diluted solution should be used immediately. If the solution is not used immediately, the in-use storage times and conditions are the responsibility of the user and are normally no longer than 12 hours at 2-8°C, provided that reconstitution/dilution has taken place in 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 they no longer use. This will help protect the environment.

6. Contents of the packaging and other information

What Piperacillin + Tazobactam Kalceks contains

• The active substances of the medicine are piperacillin and tazobactam.

Piperacillin + Tazobactam Kalceks, 2 g + 0.25 g
Each vial contains piperacillin sodium equivalent to 2 g of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam.
Piperacillin + Tazobactam Kalceks, 4 g + 0.5 g
Each vial contains piperacillin sodium equivalent to 4 g of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam.
The medicine does not contain any other ingredients.

What Piperacillin + Tazobactam Kalceks looks like and contents of the pack

Piperacillin + Tazobactam Kalceks is a white or almost white powder for solution for infusion in glass vials with blue (2 g + 0.25 g) or orange (4 g + 0.5 g) plastic caps. The vials are placed in a cardboard box.
Pack sizes: 1 or 10 vials.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

AS KALCEKS
Krustpils iela 71E
LV-1057 Rīga
Latvia
Phone: +371 67083320
Email: [email protected]

This medicine is authorized in the Member States of the European Economic Area under the following names:

Denmark
Piperacillin/Tazobactam Kalceks
Austria, Germany
Piperacillin/Tazobactam Kalceks 2 g/0.25 g Pulver zur Herstellung einer Infusionslösung
Piperacillin/Tazobactam Kalceks 4 g/0.5 g Pulver zur Herstellung einer Infusionslösung
Czech Republic, Norway, Sweden
Piperacillin/Tazobactam Kalceks
Belgium
Piperacilline/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g poeder voor oplossing voor infusie
Piperacilline/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g poudre pour solution pour perfusion
Piperacilline/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Pulver zur Herstellung einer Infusionslösung
Croatia
Piperacilin/tazobaktam Kalceks 2 g/0.25 g, 4 g/0.5 g prašak za otopinu za infuziju
Finland
Piperacillin/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g infuusiokuiva-aine, liuosta varten
France
PIPERACILLINE/TAZOBACTAM KALCEKS 2 g/0.25 g poudre pour solution pour perfusion
PIPERACILLINE/TAZOBACTAM KALCEKS 4 g/0.5 g poudre pour solution pour perfusion
Hungary
Piperacillin/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g por oldatos infúzióhoz
Ireland
Piperacillin/Tazobactam 2 g/0.25 g, 4 g/0.5 g powder for solution for infusion
Italy
Piperacillina/Tazobactam Kalceks
Latvia
Piperacillin/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g pulveris infūziju šķīduma pagatavošanai
Lithuania
Piperacillin/Tazobactam Kalceks 2000 mg/250 mg, 4000 mg/500 mg milteliai infuziniam tirpalui
Netherlands
Piperacilline/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g poeder voor oplossing voor infusie
Poland
Piperacillin + Tazobactam Kalceks
Slovenia
Piperacilin/tazobaktam Kalceks 2 g/0.25 g, 4 g/0.5 g prašek za raztopino za infundiranje
Spain
Piperacilina/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g polvo para solución para perfusión EFG

Date of last revision of the leaflet:

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Information intended for healthcare professionals only:
To obtain full information about the prescribed medicine, refer to the Summary of Product Characteristics:

Incompatibilities

Do not mix this medicinal product with other medicinal products, except for those listed below.
If piperacillin with tazobactam is used in combination with another antibiotic (e.g., an aminoglycoside), the substances must be administered separately. The combination of beta-lactam antibiotics with aminoglycosides in vitromay cause significant inactivation of the aminoglycoside.
Due to chemical instability, piperacillin with tazobactam should not be used with solutions containing only sodium bicarbonate.
Ringer's solution with lactates (Hartmann's solution) is incompatible with piperacillin and tazobactam.
Piperacillin with tazobactam should not be added to blood products or albumin hydrolysates.

Instructions for use and disposal

For single use only.
Reconstitution and dilution should be performed under aseptic conditions.
Unused solution should be discarded.
Intravenous administration
Add the volume of solvent listed in the table below to each vial, using solvents suitable for reconstitution. Mix until dissolved. After 2 minutes of continuous mixing, dissolution should occur (see detailed information below). The ready-to-use solution is clear or slightly yellowish.

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

The maximum recommended volume of sterile water for injections is 50 mL per dose.
The reconstituted solution should be withdrawn from the vial using a syringe. After dissolving the powder in the recommended manner, the contents of the vial withdrawn with a syringe will contain the amount of piperacillin and tazobactam stated on the label.

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

• 9 mg/mL (0.9%) sodium chloride solution
• 50 mg/mL (5%) glucose solution
• 50 mg/mL (5%) glucose in 9 mg/mL (0.9%) sodium chloride solution
• Ringer's solution

The solution should be inspected before use to assess its clarity. Only clear solutions free from particles should be used.
Any unused product or waste material should be disposed of in accordance with local requirements.