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
Piperacillinum + Tazobactamum
Please read carefully the entire leaflet before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Piperacillin + Tazobactam Kalceks is and what it is 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 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 can prevent the survival of certain bacteria resistant to piperacillin. This means that when piperacillin is given together with tazobactam, a broader range of bacteria can be killed.
This medicine is used:

• in adults and adolescents to treat bacterial infections such as lower respiratory tract infections (lungs), urinary tract infections (kidneys and bladder), intra-abdominal infections, skin infections, or bloodstream infections. This medicine may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
• in children aged 2 to 12 years to treat intra-abdominal infections such as appendicitis, peritonitis (infection of the fluid and lining of abdominal organs), and gallbladder or biliary tract infections. The medicine may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

In certain severe infections, the treating 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 known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may be allergic to Piperacillin + Tazobactam Kalceks.

Warnings and precautions
Before starting treatment with Piperacillin + Tazobactam Kalceks, discuss the following with your doctor, pharmacist, or nurse:

• if the patient has any allergies;
• if the patient has previously experienced diarrhoea;
• if the patient has low blood potassium levels. The doctor may recommend kidney function tests before starting treatment and regular blood tests during treatment;
• if the patient has kidney or liver problems or is undergoing haemodialysis. The doctor may recommend kidney function tests before starting treatment and regular blood tests during treatment;
• if the patient is receiving another antibiotic called vancomycin during treatment, as the risk of kidney damage may increase (see also section “Piperacillin + Tazobactam Kalceks with other medicines” in this leaflet);
• if the patient is taking certain medications (called anticoagulants) to prevent excessive blood clotting (see also “Piperacillin + Tazobactam Kalceks with other medicines” in this leaflet).

You must contact your doctor or nurse immediately:

• if the patient develops diarrhoea during or after treatment. Do not take anti-diarrhoeal medicines without consulting the doctor;
• if the patient experiences unexpected bleeding during treatment;
• if the patient has seizures during treatment;
• if the patient suspects development of a new infection or worsening of an existing one.

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

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

Piperacillin + Tazobactam Kalceks and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take, including those available without a prescription. Some medicines may interact with piperacillin and tazobactam, including:

• medicines that reduce potassium levels in the blood (e.g. diuretics or certain anticancer drugs);
• muscle relaxants used during surgery. The patient should inform the doctor about taking this medicine if undergoing general anaesthesia;
• medicines used to reduce blood clotting or treat blood clots (e.g.: heparin, warfarin, or aspirin);
• methotrexate (a medicine used in the treatment of cancer, rheumatoid arthritis, or psoriasis). Piperacillin and tazobactam may prolong the elimination of methotrexate from the body;
• a medicine used for gout (probenecid). It may prolong the elimination time of piperacillin and tazobactam from the body;
• medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform the doctor about any kidney function disorders. Concurrent use of piperacillin with tazobactam and vancomycin may increase the risk of kidney damage, even in patients without pre-existing kidney disease.

Effect on laboratory test results
Inform your doctor or laboratory staff that this medicine is being used if the patient is to provide a blood or urine sample.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Piperacillin and tazobactam may pass to the baby through the placenta or via breast milk. The decision on whether this medicine is suitable for a pregnant or breastfeeding woman will be made by the doctor.

Driving and operating machinery
This medicine is not expected to affect the ability to drive or operate machinery.

Piperacillin + Tazobactam Kalceks contains sodium
Piperacillin + Tazobactam Kalceks, 2 g + 0.25 g
This medicine contains 108 mg of sodium (the main component of table salt) per vial. This corresponds to 5.4% of the maximum recommended daily sodium intake in the adult diet.
Piperacillin + Tazobactam Kalceks, 4 g + 0.5 g
This medicine contains 216 mg of sodium (the main component of table salt) per vial. This corresponds to 10.8% of the maximum recommended daily sodium intake in the adult diet.

3. How to use Piperacillin + Tazobactam Kalceks

The medicine is administered by a doctor or nurse as an infusion (a 30-minute intravenous drip)
into one of the veins.
Dosage
The dose administered depends on the type of illness, the patient's age, and whether there are any
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 intravenously every 6 to 8 hours
(directly into the bloodstream).
Children aged 2 to 12 years
The usual dose for children with abdominal infections is 100 mg of piperacillin and 12.5 mg of tazobactam per kilogram of body weight, administered intravenously every 8 hours. The usual dose for children with low white blood cell count is 80 mg of piperacillin and 10 mg of tazobactam per kg of body weight, administered intravenously every 6 hours.
The treating 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 administered until the infection symptoms have completely resolved (for 5 to 14 days).
Patients with impaired kidney function
The treating doctor may reduce the dose or the frequency of administration. The doctor may also
recommend blood tests to ensure that the administered dose is appropriate, especially if long-term
treatment is required.
Administration of a higher than recommended dose of Piperacillin + Tazobactam Kalceks
Since the medicine is administered by a doctor or nurse, administration of an incorrect dose is unlikely.
However, if the patient experiences adverse effects such as seizures, or suspects that an excessive dose has been administered, the doctor should be informed immediately.
Missed dose of Piperacillin + Tazobactam Kalceks
If the patient suspects that a dose has been missed, they should inform the doctor or nurse immediately.
If there are any further doubts concerning the use of this medicine, consult the doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Immediately contact a doctor or nurse if the patient notices any of the following serious adverse reactions:

• severe skin reactions (Stevens-Johnson syndrome, bullous dermatitis, exfoliative dermatitis (frequency unknown), toxic epidermal necrolysis (rare)), initially appearing as red or circular spots, often with centrally located blisters, occurring on the trunk. Additional symptoms include: ulceration of the mouth, throat, nose, limbs, genitals and conjunctivae (red and swollen eyes). The rash may progress to extensive blistering or skin peeling and may potentially be life-threatening;
• a serious, potentially life-threatening allergic reaction (called "drug reaction with eosinophilia and systemic symptoms" (frequency unknown)), which may involve the skin and, more importantly, other internal organs such as the kidneys and liver;
• skin disease (called "acute generalized exanthematous pustulosis" (frequency unknown)) accompanied by fever; characterized by numerous small fluid-filled pustules located on a swollen and red large skin surface;
• 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 common);
• yellowing of the whites of the eyes or skin (frequency unknown);
• damage to blood cells (symptoms include: unexpected breathlessness, red or brown discoloration of urine, easy bruising (frequency unknown)), significant reduction in white blood cell count (rare);
• severe or persistent diarrhoea with fever or weakness (rare). If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, inform the doctor or other healthcare professional immediately.

Other adverse reactions
Very common (may affect more than 1 in 10 patients)

• diarrhoea

Common (may affect up to 1 in 10 patients)

• fungal infections (e.g. candidiasis)
• decreased platelet count, decreased red blood cell count or decreased concentration of blood pigment (haemoglobin)
• insomnia
• headache
• abdominal pain, vomiting, constipation, nausea, indigestion
• rash, itching
• fever, injection site reaction
• changes in blood tests (decreased blood protein concentration, increased liver enzyme activity in blood, abnormal blood test results indicating kidney function), 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 patients)

• reduced white blood cell count (leukopenia)
• low blood potassium levels
• seizure (convulsion), observed in patients receiving high doses of the medicine or with kidney problems
• low blood pressure, phlebitis (felt as tenderness or redness at the injection site), skin redness (erythema)
• skin reactions with redness, skin lesions, urticaria
• joint and muscle pain
• chills
• decreased blood glucose levels, increased levels of breakdown product of blood pigment (bilirubin), prolonged blood clotting time (prolonged prothrombin time)

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

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

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

• marked reduction in red blood cells, white blood cells and platelets (pancytopenia), reduced white blood cell count (neutropenia), reduced red blood cell count due to premature destruction or breakdown, increased platelet count, increased number of a certain type of white blood cells (eosinophilia)
• allergic reactions
• acute disorientation and confusion (delirium)
• lung disease in which eosinophils (a type of white blood cells) appear in increased numbers in the lungs
• hepatitis, yellowing of the skin or whites of the eyes
• small pinpoint bruises (petechiae)
• impaired kidney function and kidney diseases
• changes in blood tests (e.g.: prolonged bleeding time, increased gamma-glutamyl transferase 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 symptoms of brain dysfunction (encephalopathy) or epileptic seizures (convulsions).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide 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 on the vial label after: "EXP". The expiry date refers to the last day of the specified month.
Do not store above 30°C.
Store the vial in the outer packaging to protect from light.

Shelf life after reconstitution in the vial
After reconstitution with the appropriate solvent, chemical and physical stability of the medicine has been demonstrated for 12 hours at 25°C and for 48 hours at 2–8°C.

Shelf life after dilution of the reconstituted solution
Chemical and physical stability of the diluted reconstituted solution has been demonstrated for 12 hours at 25°C and for 48 hours at 2–8°C when diluted with Ringer's acetate, sodium chloride 9 mg/mL (0.9%), glucose 50 mg/mL (5%), glucose 50 mg/mL (5%) in sodium chloride 9 mg/mL (0.9%), using the recommended volume for further dilution.

For information on compatible diluents and volumes used for reconstitution and dilution, see "Information intended for healthcare professionals only:" below.

From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the user is responsible for the storage time and conditions prior to use, which should generally not exceed 12 hours at 2–8°C, provided that reconstitution/dilution has taken place under controlled and validated aseptic conditions.

Medicines must not be disposed of via the sewage system 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 sodium piperacillin equivalent to 2 g of piperacillin and sodium tazobactam equivalent to 0.25 g of tazobactam.
Piperacillin + Tazobactam Kalceks, 4 g + 0.5 g
Each vial contains sodium piperacillin equivalent to 4 g of piperacillin and sodium tazobactam 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 Authorisation Holder and Manufacturer
AS KALCEKS
Krustpils iela 71E
LV-1057 Rīga
Latvia
Tel.: +371 67083320
E-mail: [email protected]

This medicine is authorised for marketing in the European Economic Area countries 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

Information intended exclusively for healthcare professionals:

For complete information on the prescribed medicinal product, refer to the Summary of Product Characteristics:

Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products except those mentioned below.
If piperacillin with tazobactam is administered simultaneously with another antibiotic (e.g. an aminoglycoside), the substances must be given separately. Combining beta-lactam antibiotics with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.
Due to chemical instability, piperacillin with tazobactam should not be used with solutions containing solely sodium bicarbonate.
Ringer's lactate solution (Hartmann's solution) is incompatible with piperacillin and tazobactam.
Piperacillin with tazobactam must not be added to blood products or albumin hydrolysates.

Instructions for use and disposal
For single use only.
Reconstitution and dilution must be performed under aseptic conditions.
Discard any unused solution.

Intravenous administration
Add to each vial the volume of diluent specified in the table below, using diluents appropriate for reconstitution. Mix until dissolved. Complete dissolution should occur within 2 minutes of continuous mixing (see details 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 injections

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

The reconstituted solution may 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 acetate solution

The solution should be inspected visually before use. Only clear solutions free from particulate matter should be used.

Any unused portions of the medicinal product or waste materials should be disposed of in accordance with local regulations.