PIPERACILLIN/TAZOBACTAM QILU 4 g/0.5 g POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Piperacillin/Tazobactam Qilu 4g/0.5g 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 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 is Piperacillin/Tazobactam Qilu and what is it used for
2. What you need to know before you use Piperacillin/Tazobactam Qilu
3. How to use Piperacillin/Tazobactam Qilu
4. Possible side effects
5. Storage of Piperacillin/Tazobactam Qilu
6. Contents of the pack and other information

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

Piperacillin/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 medication 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. Piperacillin/Tazobactam can be used to treat bacterial infections in patients with low white blood cell counts (decreased resistance to infection).

This medication is indicated in children aged 2-12 years for the treatment of abdominal infections, such as appendicitis, peritonitis (infection of the fluids and membrane covering the abdominal organs), and biliary infections (infections of the gallbladder). Piperacillin/Tazobactam Qilu can be used to treat bacterial infections in patients with low white blood cell counts (decreased resistance to infection).

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

2. What you need to know before you use Piperacillin/Tazobactam Qilu

Do not use Piperacillin/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 be allergic to piperacillin/tazobactam.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Piperacillin/Tazobactam Qilu:

• If you have any allergies. If you have multiple allergies, make sure to inform your doctor or other healthcare professionals before they administer this medication to you.
• If you have had diarrhea before, during, or after treatment. In this case, make sure to inform your doctor or another healthcare professional immediately. Do not take any medication for diarrhea without discussing it with your doctor first.
• If you are taking another antibiotic called vancomycinat the same time as Piperacillin/Tazobactam Qilu, as it may increase the risk of kidney damage (see also the section Other medicines and Piperacillin/Tazobactam Qiluin this leaflet).
• If you have low potassium levels in your blood. Your doctor may want to check your kidney function before using this medication and, during treatment, may perform 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 medication and, during treatment, may perform periodic blood tests.
• If you are taking certain medications (called anticoagulants) to prevent excessive blood clot formation (see also the section Other medicines and Piperacillin/Tazobactam Qilu) or if you experience unexpected bleeding during treatment. In this case, you must inform your doctor or another healthcare professional immediately.
• If you experience seizures (epileptic crises) during treatment. In this case, you must inform your doctor or another healthcare professional.
• If you think you are suffering from a new infection or a worsening of the same. In this case, you must inform your doctor or another healthcare professional.

Hemophagocytic Lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many white blood cells, otherwise normal, called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This disease can be potentially fatal if not diagnosed and treated early. If you experience multiple symptoms, such as fever, swelling of the lymph nodes, weakness, dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

Children

The use of this medication is not recommended in children under 2 years of age due to insufficient data on safety and efficacy.

Other medicines and Piperacillin/Tazobactam Qilu

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

• Medicines for gout (probenecid). May increase the time it takes for piperacillin and tazobactam to be excreted from the body.
• Anticoagulant medicines (such as heparin, warfarin, or acetylsalicylic acid).
• Medicines used to relax muscles during surgery. If you are going to undergo 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 excreted from the body.
• Medicines that reduce potassium levels in the blood (such as diuretics or certain cancer medicines).
• Medicines containing the antibiotics tobramycin, gentamicin, or vancomycin. If you have kidney problems, inform your doctor. Taking piperacillin/tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if you do not have kidney problems.

Effects on laboratory tests

If you need to have a blood or urine test, tell your doctor or the laboratory staff that you are using 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 another healthcare professional before using this medicine. Your doctor will decide whether the use of piperacillin/tazobactam is suitable for you.

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

Driving and using machines

It is not expected that the use of this medication will affect your ability to drive or use machines.

Piperacillin/Tazobactam Qilu contains sodium.

Piperacillin/Tazobactam Qilu 4 g/0.5 g:

This medicine contains 216 mg of sodium (the main component of table salt and kitchen salt) in each vial, which is equivalent to 10.8% of the maximum recommended daily intake of sodium in food for an adult.

3. How to use Piperacillin/Tazobactam Qilu

Your doctor or another healthcare professional will administer this medication to you through an infusion (a drip over 30 minutes) into a vein.

Dosage

The dose administered to you will depend on the disease being treated, your age, and whether 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 through a vein (directly into the bloodstream).

Use in children from 2 to 12 years of age

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

Your doctor will calculate the dose based on the child's weight, but each individual dose will not exceed 4 g/0.5 g of piperacillin/tazobactam.

This medication will be administered to you until the sign of infection has completely disappeared (from 5 to 14 days).

Use in patients with kidney problems

Your doctor may need to reduce the dose of this medication or the frequency of administration. Your doctor may also want to perform blood tests to ensure that the treatment you are receiving is administered at the correct dose, especially if you need to take this medication for an extended period.

If you use more Piperacillin/Tazobactam Qilu than you should

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you miss a dose of Piperacillin/Tazobactam Qilu

If you think you have missed a dose of this medication, inform your doctor or another healthcare professional immediately.

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

4. Possible side effects

Like all medicines, this medication can cause side effects, although not everybody gets them.

If you experience any of the following serious side effects of Piperacillin/Tazobactam Qilu, see a doctor immediately:

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

• severe skin rashes (Stevens-Johnson syndrome, bullous dermatitis [frequency not known], toxic epidermal necrolysis [rare]) that initially appear as pinpoint spots or circular red patches that usually have a blister in the center. Other signs include ulcers in the mouth, throat, nose, extremities, and genitals, and conjunctivitis (red and swollen eyes). The rash can progress to extensive blistering and peeling of the skin, which can be potentially fatal.
• a severe allergic disease that can be potentially fatal (drug reaction with eosinophilia and systemic symptoms) that can affect the skin and other vital organs, such as the kidneys and liver.
• a skin disease (acute generalized exanthematous pustulosis), accompanied by fever, which is characterized by the appearance of numerous small blisters filled with fluid in 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, urine of red or brown color [frequency not known], nosebleeds [rare], bruising [frequency not known]), severe decrease in white blood cells [rare].
• severe or persistent diarrhea, accompanied by fever or weakness (rare).

If you experience any of the following side effects or any other effect not listed in this leaflet, inform your doctor or another healthcare professional.

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

• diarrhea

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

• fungal infection
• decrease in platelet count, red blood cells, or blood pigment (hemoglobin), abnormal test results (positive direct Coombs test), prolonged coagulation time (prolonged activated partial thromboplastin time)
• decrease in blood proteins
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach discomfort
• increase in liver enzymes
• skin rash, itching
• abnormal kidney test results
• fever, reaction at the injection site

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

• decrease in white blood cells (leukopenia), prolonged blood coagulation time (prolonged prothrombin time)
• decrease in potassium levels in the blood, decrease in blood glucose levels
• seizures (convulsions), observed in patients receiving high doses or with kidney problems
• low blood pressure, inflammation of the veins (sensation of sensitivity to the touch or redness of the affected area), skin redness
• increase in a breakdown product of blood pigment (bilirubin)
• skin reactions accompanied by redness, formation of 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 mouth mucosa
• peeling of the top layer of the skin all over the body (toxic epidermal necrolysis)

Frequency not known (cannot be estimated from the 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 destruction, bruising, prolonged bleeding time, increase in platelet count, increase in a specific type of white blood cells (eosinophilia)
• allergic reaction and severe allergic reaction
• inflammation of the liver, yellowing of the skin or the whites of the eyes
• severe allergic reaction that affects the whole body, accompanied by skin and mucous membrane rash, blistering, and various types of skin rash (Stevens-Johnson syndrome), severe allergic disease that affects the skin and other organs, such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small blisters filled with fluid in large areas of swollen and reddened skin, accompanied by fever (acute generalized exanthematous pustulosis), skin reactions accompanied by blistering (bullous dermatitis)
• kidney failure and kidney problems
• a type of lung disease in which there is an elevated 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 side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Piperacilina/Tazobactam Qilu

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after ‘CAD’. The expiry date refers to the last day of the month stated.

This medicine does not require any special storage conditions.

Reconstituted solution in vial

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

Diluted solution for infusion

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

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

For single use only. Discard the unused contents of the solution.

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 to protect the environment.

6. Contents of the pack and other information

Composition of Piperacilina/Tazobactam Qilu

• The active substances are piperacillin and tazobactam.

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

Appearance of Piperacilina/Tazobactam Qilu and pack contents

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

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

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation 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 medicine is authorised in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet:02/2023

Other sources of information

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

This information is intended only for healthcare professionals:

Validity period after reconstitution/dilution

Reconstituted solution in vial

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

Reconstituted solution diluted for infusion

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

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

Instructions for use

Piperacilina/Tazobactam Qilu will be administered by intravenous infusion (drip over 30 minutes).

Reconstitution and dilution of the medicine should be carried out under aseptic conditions. A visual inspection of the reconstituted/diluted solution should be performed to detect any particulate matter and changes in colour before administration. The solution should only be used if it is clear and free of particulate matter.

Preparation of the infusion solution

The powder contained in each vial should be reconstituted with the volume of solvent shown in the following table with one of the compatible reconstitution solvents. The solution should be shaken until completely dissolved. With constant shaking, reconstitution is usually completed within 5-10 minutes (see the information shown below for more detailed information on handling).

• Compatible solvents for reconstitution:

• Sodium chloride 0.9% injection solution (9 mg/ml)
• Water for injections (1)
• Glucose 5% infusion solution (50 mg/ml)

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

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

The reconstituted solutions can be further diluted to the desired volume (e.g. from 50 ml to 150 ml) with one of the following compatible solvents:

• Sodium chloride 0.9% injection solution (9 mg/ml)
• Glucose 5% infusion solution (50 mg/ml)
• Dextran 6% injection solution (60 mg/ml) in sodium chloride 0.9% solution (9 mg/ml)

Incompatibilities

When Piperacilina/Tazobactam Qilu and other antibiotics (e.g. aminoglycosides) are used simultaneously, the drugs should be administered separately. The combination of beta-lactam antibiotics and aminoglycosides in vitromay result in significant activation of the aminoglycoside.

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

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

Piperacilina/Tazobactam Qilu is not compatible with compound sodium lactate solution, Ringer's acetate solution, Ringer's acetate/malate solution, and Hartmann's solution, nor for simultaneous administration via a Y-type injection catheter.

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

Concomitant administration with aminoglycosides

Given the in vitroinactivation of aminoglycosides by beta-lactam antibiotics, it is recommended that Piperacilina/Tazobactam Qilu and the aminoglycoside be administered separately. When simultaneous treatment with aminoglycosides is indicated, Piperacilina/Tazobactam Qilu and the aminoglycoside should be reconstituted and diluted separately.