Piperacillin/tazobactam Kalceks

Package leaflet: Information for the user

Piperacillin/Tazobactam Kalceks 2 g/0,25 g powder for solution for infusion, 4 g/0,5 g powder for solution for infusion

piperacillin/tazobactam
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Piperacillina/Tazobactam Kalceks is and what it is used for

Piperacillina/Tazobactam Kalceks contains the active substances piperacillin and tazobactam.
Piperacillin belongs to a group of medicines known as "broad-spectrum penicillin antibiotics" and is capable of killing many types of bacteria. Tazobactam can prevent certain resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are administered together, they can kill a wider range of bacteria.
This medicine is used:

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

In certain severe infections, the doctor may consider using piperacillin/tazobactam in combination with other antibiotics.

2. What you should know before receiving Piperacillin/Tazobactam Kalceks

Piperacillin/Tazobactam Kalceks must not be administered to you if:

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you are given Piperacillin/Tazobactam Kalceks:

• if you have any allergies.
• if you have previously suffered from diarrhoea.
• if you have low levels of potassium in your blood. Your doctor may decide to check your kidney function before administering this medicine and may prescribe periodic blood tests during treatment.
• if you have kidney or liver problems or if you are undergoing haemodialysis. Your doctor may decide to check your kidney function before administering this medicine and may prescribe periodic blood tests during treatment.
• if you are taking another antibiotic called vancomycin. Taking piperacillin/tazobactam together with vancomycin may increase the risk of kidney damage (see also section “Other medicines and Piperacillin/Tazobactam Kalceks” in this leaflet).
• if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section “Other medicines and Piperacillin/Tazobactam Kalceks” in this leaflet).

Talk to your doctor or nurse immediately:

• if you develop diarrhoea during or after treatment. Do not take any medicine for diarrhoea without first consulting your doctor.
• if you experience unexpected bleeding during treatment.
• if you develop seizures during treatment.
• if you think you have developed a new infection or if your infection has worsened.

Haemophagocytic lymphohistiocytosis

Cases of a condition in which the immune system produces higher than normal levels of white blood cells called histiocytes and lymphocytes, leading to inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be life-threatening if not diagnosed and treated early. If you develop several symptoms such as fever, swollen lymph nodes, gland swelling, feeling weak, mental confusion, shortness of breath, bruising, 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 insufficient data on safety and efficacy.

Other medicines and Piperacillin/Tazobactam Kalceks

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription. Some medicines may interact with piperacillin and tazobactam. These include:

• medicines that can reduce potassium levels in the blood (e.g. tablets that increase urine production or certain cancer medicines).
• medicines used to relax muscles during surgery. Inform your doctor if you are undergoing general anaesthesia.
• medicines to thin the blood or treat blood clots (e.g. heparin, warfarin, or aspirin).
• methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time required for methotrexate elimination from the body.
• a medicine for gout (probenecid). It may increase the time required for elimination of piperacillin and tazobactam from the body.
• medicines containing the antibiotics tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking piperacillin/tazobactam together with vancomycin may cause acute kidney damage, even if you do not have kidney problems.

Effect on laboratory tests

Inform your doctor or laboratory staff that you are taking this medicine if you are required to provide a blood or urine sample.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before receiving this medicine.
Piperacillin and tazobactam may pass to the baby in the womb or through breast milk.
If you are pregnant or breastfeeding, your doctor will decide whether this medicine is suitable for you.

Driving and using machines

It is not expected that the use of this medicine will affect your 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 is equivalent to 5.4% of the maximum daily dietary intake recommended for an adult.

Piperacillin/Tazobactam Kalceks 4 g/0.5 g
This medicine contains 216 mg of sodium (the main component of table salt) per vial. This is equivalent to 10.8% of the maximum daily dietary intake recommended for an adult.

3. How Piperacillina/Tazobactam Kalceks is administered

The doctor or nurse will administer the medicine to you as an infusion (an intravenous drip) over 30 minutes into a vein.
Dosage
The dose administered depends on the reason for treatment, age, and whether or not you have kidney problems.
Adults and adolescents over 12 years of age
The usual dose is 4 g/0.5 g of piperacillin/tazobactam administered intravenously every 6 to 8 hours (directly into the bloodstream).
Children between 2 and 12 years of age
The usual dose for children with abdominal infections is 100 mg/12.5 mg/kg body weight of piperacillin/tazobactam administered intravenously every 8 hours. The usual dose for children with low white blood cell counts is 80 mg/10 mg/kg body weight of piperacillin/tazobactam administered intravenously every 6 hours.
The doctor will calculate the dose based on the child's body weight, but each single dose must not exceed 4 g/0.5 g of piperacillin/tazobactam.
The medicine will be administered until all signs of infection have completely disappeared (from 5 to 14 days).
Patients with kidney problems
The doctor may need to reduce the dose or the frequency of administration of this medicine. The doctor may also perform blood tests to ensure that the prescribed dose is appropriate, especially if you are to take this medicine for a prolonged period.
If you use more Piperacillina/Tazobactam Kalceks than you should
Since you will receive this medicine from a doctor or nurse, it is unlikely that you will be given an incorrect dose. If you think you have received an excessive dose of the medicine or if you experience adverse effects such as seizures, inform the doctor immediately.
If you forget to use Piperacillina/Tazobactam Kalceks
If you think you have missed a dose of this medicine, inform the doctor or nurse immediately.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any of the potentially serious side effects listed below, consult your doctor or nurse immediately:

• severe skin reactions (Stevens-Johnson syndrome, bullous dermatitis, exfoliative dermatitis (frequency not known), and toxic epidermal necrolysis (rare)), which initially present as reddish patches or circular rashes, often with central blisters, usually on the trunk. Further symptoms include ulcers in the mouth, throat, nose, extremities, genitals, and conjunctivitis (red and swollen eyes). The rash may progress to widespread blistering or skin peeling, which can potentially be life-threatening;
• a severe, potentially fatal allergic reaction (called "drug reaction with eosinophilia and systemic symptoms" (frequency not known)), which may affect the skin and particularly other internal organs such as the kidneys and liver;
• a skin condition (called "acute generalized exanthematous pustulosis") (frequency not known), accompanied by fever, consisting of numerous small fluid-filled pustules within large areas of swollen and reddened 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 on the skin (uncommon);
• yellowing of the eyes or skin (frequency not known);
• damage to blood cells (signs include: unexpected breathlessness, red or brown urine, pinpoint bruises) (frequency not known), severe decrease in white blood cells (rare);
• severe or persistent diarrhoea accompanied by fever or weakness (rare). If any of the following side effects becomes severe or if you notice any side effect not listed in this leaflet, inform your doctor or another healthcare professional.

Other side effects:
Very common (may affect more than 1 in 10 people)

• diarrhoea

Common (may affect up to 1 in 10 people)

• fungal infections
• reduced platelet count, reduced red blood cell count or blood pigment/haemoglobin
• insomnia
• headache
• abdominal pain, vomiting, constipation, nausea, stomach discomfort
• skin rash, itching
• fever, injection site reaction
• changes in blood tests (decreased blood proteins, increased liver enzymes in blood, kidney function test abnormalities), laboratory test abnormalities (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time)

Uncommon (may affect up to 1 in 100 people)

• reduced white blood cell count (leucopenia)
• low potassium levels in the blood (hypokalaemia)
• seizures, reported in patients receiving high doses or with kidney problems
• low blood pressure, inflammation of veins (felt as tenderness or redness in the affected area), skin flushing
• skin reactions with redness, skin lesions, hives
• joint and muscle pain
• chills
• decreased blood sugar (glucose), increased breakdown product of blood pigments (bilirubin), prolonged blood clotting time (prolonged prothrombin time)

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

• nosebleeds
• inflammation of the mouth mucosa

Not known (frequency cannot be estimated from the available data)

• severe reduction in red blood cells, white blood cells, and platelets (pancytopenia), reduced white blood cells (neutropenia), reduced red blood cells due to premature breakdown, increased platelet count, increase in a specific type of white blood cells (eosinophilia)
• allergic reactions
• acute disorientation and confusion (delirium)
• a form of lung disease in which eosinophils (a type of white blood cells) appear in increased numbers in the lungs
• liver inflammation, yellowing of the skin or whites of the eyes
• pinpoint bruising (purpura)
• impaired kidney function and kidney problems
• changes in blood tests (e.g. prolonged bleeding time, increased gamma-glutamyl transferase)

Treatment with piperacillin has been associated with a higher incidence of fever and rash in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin/tazobactam, may cause signs of altered brain function (encephalopathy) and seizures (fits).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Piperacillin/Tazobactam Kalceks

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial, after “Exp.” or “EXP”. The expiry date refers to the last day of that month.
Do not store above 30 °C.
Keep the vial in the outer packaging to protect the medicine from light.

Shelf life after reconstitution in the vial
Chemical and physical in-use stability has been demonstrated for 12 hours at 25 °C and for 48 hours at 2–8 °C, when reconstituted with one of the compatible solvents for reconstitution.

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 48 hours at 2–8 °C, when diluted with Ringer's acetate 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, at the recommended dilution volume for further dilution.

For information on compatible solutions and volumes used for reconstitution and dilution, see "The following information is intended exclusively for doctors or healthcare professionals."

From a microbiological standpoint, diluted solutions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not exceed 12 hours at 2–8 °C, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents 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.
No other components are present.

Description of the appearance of Piperacillin/Tazobactam Kalceks and package contents
Piperacillin/Tazobactam Kalceks is a white to off-white powder for solution for infusion in glass vials with blue (2 g/0.25 g) or orange (4 g/0.5 g) plastic stoppers. The vials are packaged in cardboard boxes.
Pack sizes: 1 or 10 vials
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
AS KALCEKS
Krustpils iela 71E, Rīga, LV-1057, Latvia
Tel.: +371 67083320
E-mail: [email protected]

This medicinal product is authorised 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 Piperacilin/tazobaktam 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
infusion, for solution
France PIPERACILLINE/TAZOBACTAM KALCEKS 2 g/0.25 g powder for
solution for perfusion
PIPERACILLINE/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 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 infusion
Lithuania Piperacillin/Tazobactam Kalceks 2000 mg/250 mg, 4000 mg/500 mg
powder for infusion solution
Netherlands Piperacillin/Tazobactam Kalceks 2 g/0.25 g, 4 g/0.5 g powder for
solution for infusion
Poland Piperacillin + Tazobactam Kalceks
Slovenia Piperacilin/tazobaktam 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 EFG

The following information is intended for healthcare professionals only:
Refer to the Summary of Product Characteristics for complete prescribing information.

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned below.
When piperacillin/tazobactam is used concomitantly with another antibiotic (e.g. aminoglycosides), the substances must be administered separately. Mixing beta-lactam antibiotics with an aminoglycoside in vitro may cause substantial inactivation of the aminoglycoside.
Due to chemical instability, piperacillin/tazobactam must not be used in solutions containing sodium bicarbonate only.
Ringer's lactate solution (Hartmann's solution) is incompatible with piperacillin/tazobactam.
Piperacillin/tazobactam must not be added to blood derivatives or albumin hydrolysates.

Instructions for use and other handling
For single use only.
Reconstitution and dilution must be carried out under aseptic conditions. Any unused solution must be discarded.

Intravenous use
Reconstitute each vial with the volume of solvent indicated in the table below, using one of the compatible solvents for reconstitution. Shake until dissolved. If shaken continuously, reconstitution is generally achieved within 2 minutes (for details on handling, see below). The reconstituted solution ranges from colourless to yellowish.

* Compatible solvents for reconstitution:

• sodium chloride solution 9 mg/ml (0.9%)
• glucose solution 50 mg/ml (5%)
• glucose solution 50 mg/ml (5%) in sodium chloride solution 9 mg/ml (0.9%)
• water for injections

The maximum recommended volume of sterile water for injections for each dose is 50 ml.
The reconstituted solution should be withdrawn from the vial using a syringe. Once reconstituted
according to the instructions, the content of the vial withdrawn with the syringe will provide the amount of
piperacillin and tazobactam stated on the label.
The reconstituted solutions may be further diluted to the desired volume (e.g. from 50 ml to
150 ml) with one of the following compatible solvents:

• sodium chloride solution 9 mg/ml (0.9%)
• glucose solution 50 mg/ml (5%)
• glucose solution 50 mg/ml (5%) in sodium chloride solution 9 mg/ml (0.9%)
• Ringer acetate solution

The solution should be inspected visually before use. Only clear solutions free from particles should be used.
Any unused medicinal product and waste material derived from this medicinal product should be disposed of in accordance with local regulations.