Piperacillin/tazobactam Qilu 2 g/0.25 g powder for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Piperacilina/Tazobactam Qilu 2g/0.25g powder for solution for infusion EFG

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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Piperacilina/Tazobactam Qilu is and what it is used for

Piperacilina/Tazobactam Qilu contains the active substances piperacillin and tazobactam.

Piperacillin belongs to a group of medicines known as "broad-spectrum penicillin antibiotics" and can kill many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin; that is, when piperacillin and tazobactam are administered together, more types of bacteria are killed.

This medicine is indicated in adults and adolescents for the treatment of bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin, or blood. Piperacilina/Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

This medicine is indicated in children aged 2–12 years for the treatment of abdominal infections, such as appendicitis, peritonitis (infection of the fluids and the membrane lining the abdominal organs), and biliary tract infections. Piperacilina/Tazobactam Qilu 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 using piperacillin/tazobactam in combination with other antibiotics.

2. What you need to know before using Piperacilina/Tazobactam Qilu

Do not use Piperacilina/Tazobactam Qilu

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Piperacilina/Tazobactam Qilu:

• If you have any allergies. If you suffer from multiple allergies, make sure to inform your doctor or other healthcare professionals before receiving this medicine.
• If you have diarrhea before, during, or after treatment. In this case, inform your doctor or other healthcare professional immediately. Do not take any medication for diarrhea without first discussing it with your doctor.
• If you are taking another antibiotic called vancomycin at the same time as Piperacilina/Tazobactam Qilu, as this may increase the risk of kidney injury (see also section Other medicines and Piperacilina/Tazobactam Qilu in this leaflet).
• If you have low blood potassium levels. Your doctor may want to check your kidney function before using this medicine, and during treatment, you may require periodic blood tests.
• If you have kidney or liver problems or are undergoing hemodialysis. Your doctor may want to check your kidney function before using this medicine, and during treatment, you may require periodic blood tests.
• If you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section Other medicines and Piperacilina/Tazobactam Qilu) or if unexpected bleeding occurs during treatment. In this case, inform your doctor or other healthcare professional immediately.
• If you experience seizures (epileptic fits) during treatment. In this case, inform your doctor or other healthcare professional.
• If you suspect you are developing a new infection or worsening of an existing one. In this case, inform your doctor or other healthcare professional.

Haemophagocytic lymphohistiocytosis

Cases of a disease in which the immune system produces excessive numbers of otherwise normal white blood cells called lymphocytes and histiocytes, leading to inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be potentially fatal if not diagnosed and treated early. If you experience multiple symptoms such as fever, swollen lymph nodes, weakness, dizziness, difficulty breathing, 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 Piperacilina/Tazobactam Qilu

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

• Medicines for gout (probenecid). This may increase the time it takes for piperacillin and tazobactam to be eliminated from the body.
• Anticoagulant medicines (such as heparin, warfarin, or acetylsalicylic acid).
• Medicines used to relax muscles during surgery. If you are undergoing general anesthesia, inform your doctor.
• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time it takes for methotrexate to be eliminated from the body.
• Medicines that reduce potassium levels in the blood (such as diuretics or certain cancer treatments).
• Medicines containing the antibiotics tobramycin, gentamicin, or vancomycin. If you have kidney problems, inform your doctor. Taking Piperacilina/Tazobactam and vancomycin together may increase the risk of kidney injury, even in the absence of pre-existing kidney problems.

Effects on laboratory tests

If you need to have blood or urine tests, inform your doctor or clinical laboratory staff that you are taking piperacillin/tazobactam.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or other healthcare professional before using this medicine. Your doctor will decide whether the use of piperacillin/tazobactam is appropriate for you.

Piperacillin and tazobactam may cross the placenta and reach the fetus or may be excreted in breast milk. If you are breastfeeding, your doctor will decide whether this medicine is suitable for you.

Driving and using machines

Piperacilina/Tazobactam Qilu is not expected to affect your ability to drive or operate machinery.

Piperacilina/Tazobactam Qilu contains sodium.

Piperacilina/Tazobactam Qilu 2 g/0.25 g:

This medicine contains 108 mg of sodium (a main component of household and cooking salt) per vial, equivalent to 5.4% of the maximum daily recommended sodium intake from food for an adult.

3. How to use Piperacillin/Tazobactam Qilu

Your doctor or another healthcare professional will administer this medicine by intravenous infusion (a drip over 30 minutes) into a vein.

Posology

The dose you are given depends on the infection being treated, your 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 every 6–8 hours via intravenous route (directly into the bloodstream).

Use in children aged 2 to 12 years

The usual dose for children with abdominal infections is 100 mg/12.5 mg/kg body weight of piperacillin/tazobactam, administered every 8 hours intravenously (directly into the bloodstream). The usual dose for children with low white blood cell count is 80 mg/10 mg/kg body weight of piperacillin/tazobactam, administered every 6 hours intravenously (directly into the bloodstream).

Your doctor will calculate the dose based on the child's body weight, but no single dose should exceed 4 g/0.5 g of piperacillin/tazobactam.

You will be given this medicine until the signs of infection have completely disappeared (for 5 to 14 days).

Use in patients with kidney problems

Your doctor may need to reduce the dose or the frequency of administration. Your doctor may also wish to perform blood tests to ensure that your treatment is being given at the correct dose, especially if you need to take this medicine for a prolonged period.

If you use more Piperacillin/Tazobactam Qilu than you should

Since this medicine is administered by a doctor or healthcare professional, it is highly unlikely that you will be given an incorrect dose. However, if you experience adverse effects such as seizures (epileptic fits), or if you think you have been given too much medicine, inform your doctor immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately, or call the Toxicology Information Service at telephone number 91 562 04 20, stating the name of the medicine and the amount ingested.

If you forget to use Piperacillin/Tazobactam Qilu

If you think a dose of this medicine has not been administered, inform your doctor or another healthcare professional immediately.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

If you experience any of the following serious adverse effects of Piperacillin/Tazobactam Qilu, seek immediate medical attention:

Serious adverse effects (with their frequency in parentheses or brackets) of piperacillin/tazobactam are:

• severe skin rashes (Stevens-Johnson syndrome, bullous dermatitis [frequency not known], toxic epidermal necrolysis [rare]), which initially appear as pinpoint spots or circular red patches, often with a blister at the center. Other signs include ulcers in the mouth, throat, nose, limbs, and genitals, and conjunctivitis (red and swollen eyes). The rash may progress to widespread blistering and peeling of the skin, which can be life-threatening.
• severe, potentially life-threatening allergic disease (drug reaction with eosinophilia and systemic symptoms), which may affect the skin and vital organs such as the kidneys and liver.
• a skin condition (acute generalized exanthematous pustulosis), accompanied by fever, characterized by the appearance of numerous small fluid-filled blisters on 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 blisters (uncommon), itching or skin rash (common).
• yellowing of the eyes or skin (frequency not known).
• damage to blood cells (signs include unexpected shortness of breath, red or brown urine [frequency not known], nosebleeds [rare], bruising [frequency not known]), severe decrease in white blood cells [rare].
• acute or persistent diarrhea, accompanied by fever or weakness (rare).

If you experience any of the following adverse effects or any other unlisted effect not mentioned in this leaflet, inform your doctor or other healthcare professional.

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

• diarrhea

Common (may affect up to 1 in 10 people):

• fungal infection
• decreased platelet, red blood cell, or blood pigment (hemoglobin) counts; abnormal laboratory test results (positive direct Coombs test); prolonged blood clotting time (prolonged activated partial thromboplastin time)
• decreased protein levels in the blood
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach discomfort
• increased liver enzymes
• skin rash, itching
• abnormal kidney function test results
• fever, injection site reaction

Uncommon (may affect up to 1 in 100 people):

• decreased white blood cells (leukopenia); prolonged blood clotting time (prolonged prothrombin time)
• low blood potassium, low blood glucose
• seizures, observed in patients receiving high doses or with kidney problems
• low blood pressure, vein inflammation (tenderness or redness in the affected area), skin redness
• increased levels of a blood pigment breakdown product (bilirubin)
• skin reactions with redness, skin lesions, and urticarial rash
• joint and muscle pain
• chills

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

• severe decrease in white blood cells (agranulocytosis), nosebleeds
• severe colon infection, inflammation of the mucous membrane of the mouth
• detachment of the upper layer of skin throughout the body (toxic epidermal necrolysis)

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

• severe decrease in red blood cells, white blood cells, and platelets (pancytopenia); decrease in white blood cells (neutropenia); decrease in red blood cells due to premature breakdown or destruction; bruising; prolonged bleeding time; increased platelet count; increase in a specific type of white blood cell (eosinophilia)
• allergic reaction and severe allergic reaction
• liver inflammation, yellowing of the skin or whites of the eyes
• widespread, severe allergic reaction affecting the entire body, accompanied by skin and mucosal rash, blistering, and various types of skin eruptions (Stevens-Johnson syndrome); severe allergic disease affecting the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms); numerous small fluid-filled blisters on large areas of swollen and reddened skin, accompanied by fever (acute generalized exanthematous pustulosis); skin reactions with blister formation (bullous dermatitis)
• kidney failure and kidney problems
• a type of lung disease characterized by a high number of eosinophils (a type of white blood cell) in the lungs
• acute disorientation and confusion (delirium)

Treatment with piperacillin has been associated with an increased incidence of fever and rash in patients with cystic fibrosis.

Beta-lactam antibiotics, including piperacillin/tazobactam, may cause manifestations of encephalopathy (brain damage or disease) and seizures (convulsions).

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Piperacillin/Tazobactam Qilu

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 after "EXP". The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Reconstituted solution in vial

Chemical and physical in-use stability has been demonstrated for up to 48 hours when stored refrigerated at 2-8°C, and for up to 5 hours when stored at 20-25°C, following reconstitution with one of the compatible solvents for reconstitution (see section 6.6).

Diluted solution for infusion

Chemical and physical in-use stability has been demonstrated for up to 48 hours when stored refrigerated at 2-8°C, and for up to 6 hours when stored at 20-25°C, following reconstitution with one of the compatible solvents diluted to the recommended dilution volume (see section 6.6).

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2-8°C, unless reconstitution/dilution (etc.) has been carried out under controlled and validated aseptic conditions.

For single use only. Discard any unused solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Doing so will help protect the environment.

6. Contents of the container and other information

Composition of Piperacillin/Tazobactam Qilu

• The active substances are piperacillin and tazobactam.

Each vial contains 2 g of piperacillin (as sodium piperacillin) and 0.25 g of tazobactam (as sodium tazobactam).

Appearance of Piperacillin/Tazobactam Qilu and contents of the container

Piperacillin/Tazobactam Qilu 2 g/0.25 g is a compact powder for suspension or a white to off-white powder, available in 30 ml glass vials with bromobutyl rubber stoppers and aluminum-plastic combination caps.

Pack sizes: 1, 5, 10, 12, 25 or 50 vials per carton.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

QILU PHARMA SPAIN S.L.

Paseo de la Castellana 40,

8th floor, 28046 - Madrid,

Spain

Manufacturer

Kymos, S.L.

Ronda De Can Fatjó 7b,

Parc Tecnologic Del Valles Cerdanyola Del Vallès,

08290 Barcelona,

Spain

or

Unifarma SIA

Vangazu Iela 23,

1024 Riga,

Latvia

or

EUROFINS BIOPHARMA PRODUCT TESTING BUDAPEST Kft.

Anonymus utca 6.,

1045 Budapest IV,

Hungary

Local representative:

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya, 53-55

08007 – Barcelona

Spain

Tel.: +34 93 342 7890

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

Germany	Piperacillin/Tazobactam Qilu 2 g/0.25 g powder for solution for infusion
Spain	Piperacillin/Tazobactam Qilu 2 g/0.25 g powder for solution for infusion EFG
France	PIPERACILLIN/TAZOBACTAM QILU 2 g/0.25 g, powder for solution for infusion
Italy	Piperacillin/Tazobactam Qilu
Finland	Piperacillin/Tazobactam Qilu 2 g/0.25 g powder for infusion, solution for use
Denmark	Piperacillin/Tazobactam Qilu
Norway	Piperacillin/Tazobactam Qilu
Sweden	Piperacillin/Tazobactam Qilu 2 g/0.25 g powder for infusion solution, solution

Date of the most recent review of this leaflet: 02/2023

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Shelf-life after reconstitution/dilution

Reconstituted solution in vial

Chemical and physical in-use stability has been demonstrated for up to 48 hours when stored refrigerated at 2-8°C, and for up to 5 hours when stored at 20-25°C, after reconstitution with one of the compatible solvents for reconstitution (see section 6.6).

Diluted reconstituted solution for infusion

Chemical and physical in-use stability has been demonstrated for up to 48 hours when stored refrigerated at 2-8°C, and for up to 6 hours when stored at 20-25°C, after reconstitution with one of the compatible solvents for dilution at the recommended dilution volume (see section 6.6).

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless reconstitution/dilution (etc.) has been carried out under controlled and validated aseptic conditions.

Instructions for use

Piperacilina/Tazobactam Qilu is to be administered by intravenous infusion (infusion bag over 30 minutes).

Reconstitution and dilution of the medicinal product must be performed under aseptic conditions. The reconstituted/diluted solution should be visually inspected for particulate matter and discoloration prior to administration. The solution should only be used if it is clear and free of particulate matter.

Preparation of the infusion solution

The powder in each vial must be reconstituted with the volume of solvent indicated in the table below, using one of the compatible reconstitution solvents. The solution should be shaken until complete dissolution is achieved. With continuous agitation, reconstitution is usually complete within 5-10 minutes (refer to the information provided below for further detailed handling instructions).

Content of vial	Volume of solvent* to be added to each vial	Approximate concentration after reconstitution
2 g/0.25 g (2 g of piperacillin and 0.25 g of tazobactam)	10 ml	193.2 mg/ml (containing 171.7 mg/ml of piperacillin and 21.5 mg/ml of tazobactam)

• Compatible solvents for reconstitution:

• 0.9% (9 mg/ml) sodium chloride injection solution

• Water for injections (1)

• 5% (50 mg/ml) glucose infusion solution

(1) The maximum recommended volume of water for injections per dose is 50 ml.

Reconstituted solutions should be withdrawn from the vial using a syringe. If the vial contents are reconstituted as directed, withdrawal with a syringe will provide the stated amount of piperacillin and tazobactam.

Reconstituted solutions may be further diluted to the desired volume (e.g., from 50 ml to 150 ml) with one of the following compatible diluents:

• 0.9% (9 mg/ml) sodium chloride injection solution
• 5% (50 mg/ml) glucose infusion solution
• 6% (60 mg/ml) dextran solution in 0.9% (9 mg/ml) sodium chloride solution

Incompatibilities

Whenever Piperacilina/Tazobactam Qilu is used concomitantly with other antibiotics (e.g., aminoglycosides), the drugs should be administered separately. The combination of beta-lactam antibiotics and aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.

Piperacilina/Tazobactam Qilu must not be mixed with other drugs in a syringe or infusion bottle, as compatibility has not been established.

Piperacilina/Tazobactam Qilu must not be used in solutions containing only sodium bicarbonate due to its chemical instability.

Piperacilina/Tazobactam Qilu is incompatible with compound sodium lactate solution, Ringer's acetate solution, Ringer's acetate/malate solution, and Hartmann's solution, as well as for co-administration through a Y-injection catheter.

Piperacilina/Tazobactam Qilu must not be added to blood products or albumin hydrolysates.

Concomitant administration with aminoglycosides

Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, separate administration of Piperacilina/Tazobactam Qilu and aminoglycosides is recommended. When concomitant treatment with aminoglycosides is indicated, Piperacilina/Tazobactam Qilu and the aminoglycoside should be reconstituted and diluted separately.