Piperacillin + Tazobactam Kalceks

Package Leaflet: 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 all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

• 1. What Piperacillin + Tazobactam Kalceks is and what it is used for
• 2. What you need to know before you use 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 pack and other information

1. What Piperacillin + Tazobactam Kalceks is and what it is 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 may prevent some bacteria that are not sensitive to piperacillin from developing resistance.
This means that if piperacillin is given together with tazobactam, more types of bacteria can be killed.
The medicine is used:

• in adults and adolescentsto treat bacterial infections such as infections of the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdominal cavity, skin, or blood. This medicine may be used to treat bacterial infections in patients with a low number of white blood cells (with reduced resistance to infections).
• in children aged 2 to 12 yearsto treat abdominal 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 number of white blood cells (with reduced resistance to infections).

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

2. What you need to know before you use Piperacillin + Tazobactam Kalceks

Do not use Piperacillin + Tazobactam Kalceks:

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

Warnings and precautions

Before you start using Piperacillin + Tazobactam Kalceks, tell your doctor, pharmacist, or nurse:

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

Tell your doctor or nurse immediatelyif:

• you get diarrhea during or after treatment. Do not take anti-diarrheal medicines without consulting your doctor;
• you experience unexpected bleeding during treatment;
• you have seizures during treatment;
• you think you have developed a new or worsening infection.

Hemophagocytic lymphohistiocytosis
There have been reports of a condition where 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 you experience multiple symptoms such as fever, swollen lymph nodes, feeling weak, dizziness, shortness of breath, bluish discoloration, or skin rash, contact your doctor immediately.

Children

The use of this medicine is not recommended in children under 2 years of age due to the lack of sufficient data on safety and efficacy.

Piperacillin + Tazobactam Kalceks and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription. Some medicines may interact with piperacillin and tazobactam. These include:

• medicines that lower potassium levels in the blood (e.g., diuretics or certain anticancer medicines);
• muscle relaxants used during surgery. You should inform your doctor about the use of this medicine if you 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. You should inform your 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 tests
Tell your doctor or laboratory staff that you are using this medicine if you are to have a blood or urine test.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Piperacillin and tazobactam may pass into the baby's body through the placenta or into breast milk.
The decision to use this medicine during pregnancy or breastfeeding is made by the doctor.

Driving and using machines

Using this medicine should not affect your ability to drive or use 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) in each 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) in each 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 as an infusion (drip) into a vein for 30 minutes.

Dosage

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

Adults and adolescents over 12 years

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

Children aged 2 to 12 years

The usual dose for abdominal infections is 100 mg of piperacillin and 12.5 mg of tazobactam per kilogram of body weight given into a vein every 8 hours. The usual dose for patients with a low number of white blood cells is 80 mg of piperacillin and 10 mg of tazobactam per kilogram of body weight given into a vein every 6 hours.
The doctor will calculate the dose based on the child's body weight, assuming that the individual dose does not exceed 4 g of piperacillin and 0.5 g of tazobactam.
The medicine is used until the infection symptoms disappear (for 5 to 14 days).

Patients with kidney problems

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

Using more than the recommended dose of Piperacillin + Tazobactam Kalceks

The medicine is given by a doctor or nurse, so using an incorrect dose is unlikely. However, if you experience side effects such as seizures or think you have received too much medicine, tell your doctor immediately.

Missing a dose of Piperacillin + Tazobactam Kalceks

If you think you have missed a dose, tell your doctor or nurse immediately.
If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediatelyif you notice any of the following serious side effects:

• severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme (frequency not known), drug rash with eosinophilia and systemic symptoms (DRESS) (frequency not known)) initially appearing as red or circular patches, often with centrally located blisters, occurring on the torso. Additional symptoms include ulcers in the mouth, throat, nose, limbs, genitals, and conjunctivitis (red and swollen eyes). The rash may develop into widespread blisters or skin peeling and can 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 swollen and red large areas of skin;
• 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 include unexpected shortness of breath, red or brown urine, small bruises (frequency not known)), significant decrease in the number of white blood cells (rare);
• severe or persistent diarrhea with fever or weakness (rare). If you experience anyof these side effects or any other side effects not listed in this leaflet, tell your doctor or nurse.

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
• decrease in the number of platelets, red blood cells, or hemoglobin in the blood
• insomnia
• headache
• abdominal pain, vomiting, constipation, nausea, indigestion
• rash, itching
• fever, reaction at the injection site
• changes in blood tests (decrease in blood protein, increase in liver enzyme activity, abnormal kidney function tests), 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)

• decrease in the number of white blood cells (leukopenia)
• decrease in 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
• decrease in blood sugar, increase in bilirubin, prolonged blood clotting time (prolonged prothrombin time)

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

• nosebleeds
• mouth inflammation

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

• significant decrease in the number of red blood cells, white blood cells, and platelets (pancytopenia), decrease in the number of white blood cells (neutropenia), decrease in red blood cells due to their premature breakdown or degradation, increase in the number of platelets, increase in the number 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 damage 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 dysfunction (encephalopathy) or seizures.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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 will help to gather more information on the safety of this medicine.

5. How to store Piperacillin + Tazobactam Kalceks

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 vial label after "EXP". The expiry date refers to the last day of that month.
Do not store above 30°C.
Store the vial in the outer carton to protect 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 diluted solution after reconstitution 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.
For 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 not used immediately, the 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 was 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 pack and other information

What Piperacillin + Tazobactam Kalceks contains

• The active substances 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 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 packaged in a carton.
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: kalceks@kalceks.lv

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 Powder for solution for infusion
Piperacillin + Tazobactam Kalceks 4 g/0.5 g Powder for solution for infusion
Czech Republic, Norway, Sweden
Piperacillin + Tazobactam Kalceks
Belgium
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for perfusion
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Croatia
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Finland
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
France
Piperacillin + Tazobactam Kalceks 2 g/0.25 g Powder for solution for perfusion
Piperacillin + Tazobactam Kalceks 4 g/0.5 g Powder for solution for perfusion
Hungary
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Ireland
Piperacillin + Tazobactam 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Italy
Piperacillin + Tazobactam Kalceks
Latvia
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Lithuania
Piperacillin + Tazobactam Kalceks 2000 mg/250 mg, 4000 mg/500 mg Powder for solution for infusion
Netherlands
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Poland
Piperacillin + Tazobactam Kalceks
Slovenia
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for infusion
Spain
Piperacillin + Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g Powder for solution for perfusion

Date of last revision of the leaflet:

------------------------------------------------------------------------------------------------------------------------
Information intended for healthcare professionals only:
To obtain full information about the medicinal product, consult the Summary of Product Characteristics:

Incompatibilities

Do not mix this medicinal product with other medicinal products except those mentioned 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 lactate (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 carried out under aseptic conditions.
Unused solution should be discarded.
Intravenous administration
Add the volume of solvent shown 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 resulting 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 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 dissolution of the powder in the recommended manner, the contents of the vial withdrawn with a syringe will contain the labeled amount of piperacillin and tazobactam.

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 visually before use. Only clear solutions free from particles should be used.
Any unused product or waste material should be disposed of in accordance with local requirements.