Prospecto: information for the patient

Piperacilina/Tazobactam Qilu 2g/0,25g powder for solution for infusion EFG

Read this prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospectus. See section 4.

1. What isPiperacilina/Tazobactam Qiluand what is it used for

2. What you need to know before starting to usePiperacilina/Tazobactam Qilu

3. How to usePiperacilina/Tazobactam Qilu

4. Possible adverse effects

5. Storage ofPiperacilina/Tazobactam Qilu

6. Contents of the package and additional information

Piperacilina/Tazobactam Qilu contains the active ingredients piperacilina and tazobactam.

Piperacilina belongs to a group of medicines known as «broad-spectrum penicillin class antibiotics» and can kill many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacilina; that is, when piperacilina and tazobactam are administered at the same time, more types of bacteria are killed.

This medicine is indicated for adults and adolescents in the treatment of bacterial infections, such as those affecting the lower respiratory tracts (lungs), urinary tracts (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 for children aged 2-12 years in the treatment of abdominal infections, such as appendicitis, peritonitis (infection of the liquids and membrane covering 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 the use of piperacilina/tazobactam in combination with other antibiotics.

No use Piperacilina/Tazobactam Qilu

• if you are allergic to piperacilina or tazobactam.
• if you are allergic to known antibiotics such as penicilinas, cefalosporinas, or other beta-lactamase inhibitors, as you may be allergic to piperacilina/tazobactam.

Advertencias y precauciones

Consult your doctor, pharmacist, or nurse before starting to use Piperacilina/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 other healthcare professional immediately. Do not take any medication for diarrhea without having spoken to your doctor first.
• If you are taking another antibiotic called vancomicina at the same time as Piperacilina/Tazobactam Qilu, as it may increase the risk of kidney damage (see also the section Otros medicamentos y Piperacilina/Tazobactam Qilu in this leaflet).
• If you have a low potassium level in your blood. Your doctor may want to check your kidney function before using this medication and, during treatment, you may have periodic blood tests.
• If you have kidney or liver problems or are undergoing hemodiálisis. Your doctor may want to check your kidney function before using this medication and, during treatment, you may have periodic blood tests.
• If you are taking certain medications (called anticoagulantes) to prevent excessive blood clotting (see also the section Otros medicamentos y Piperacilina/Tazobactam Qilu) or if you experience unexpected bleeding during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• If you experience seizures (epileptic crises) during treatment. In this case, you must inform your doctor or other healthcare professional.
• If you believe you are experiencing a new infection or a worsening of the same. In this case, you must inform your doctor or other healthcare professional.

Linfohistiocitosis hemofagocítica

Cases of a disease in which the immune system produces too many otherwise normal white blood cells called histiocitos and linfocitos, causing inflammation (linfohistiocitosis hemofagocítica) have been reported. This disease can be potentially fatal if not diagnosed and treated promptly. If you experience multiple symptoms such as fever, swelling of lymph nodes, feeling of weakness, feeling of dizziness, difficulty breathing, bruises, or skin rash, contact your doctor immediately.

Niños

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

Otros medicamentos y Piperacilina/Tazobactam Qilu

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications. Some medications may interact with piperacilina and tazobactam, including:

• Medications for gout (probenecid). It may increase the time it takes for piperacilina and tazobactam to be excreted from the body.
• Anticoagulant medications (such as heparin, warfarin, or aspirin).
• Medications used to relax muscles during surgery. If you are undergoing general anesthesia, inform your doctor.
• Methotrexate (a medication used to treat cancer, arthritis, or psoriasis). Piperacilina and tazobactam may increase the time it takes for methotrexate to be excreted from the body.
• Medications that reduce potassium levels in the blood (such as diuretics or some cancer medications).
• Medications containing the antibiotics tobramicina, gentamicina, or vancomicina. If you have kidney problems, inform your doctor. The simultaneous use of Piperacilina/Tazobactam and vancomicina may increase the risk of kidney damage, even if you do not have kidney problems.

Efectos en las pruebas analíticas

If you need to have a blood or urine test, inform your doctor or the clinical laboratory staff that you are using piperacilina/tazobactam.

Embarazo y lactancia

If you are pregnant or breastfeeding, or if you believe you may be pregnant, consult your doctor or other healthcare professional before using this medication. Your doctor will decide if the use of piperacilina/tazobactam is suitable for you.

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

Conducción y uso de máquinas

No se prevé que el uso de este medicamento afecte a la capacidad para conducir o usar máquinas.

Piperacilina/Tazobactam Qilu contiene sodio.

Piperacilina/Tazobactam Qilu 2 g/0.25 g:

This medication contains 108 mg of sodium (main component of table salt and cooking salt) in each vial, which is equivalent to 5.4% of the maximum recommended daily sodium intake in meals for an adult.

Your doctor or other healthcare professional will administer this medication through an infusion (a drip for 30 minutes) in a vein.

Dosage

The dose they administer will depend on the disease being treated, your age, and whether you have any 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 aged 2 to 12 years

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 count 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.

They will administer this medication until the infection sign has completely disappeared (5 to 14 days).

Use in patients with kidney problems

Your doctor may need to reduce the dose of this medication or the frequency with which it is administered. They may also want to do 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 a prolonged period.

If you use more Piperacillin/tazobactam Qilu than you should

Since this medication will be administered by a doctor or other 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 believe 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 Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Piperacillin/Tazobactam Qilu

If you believe you have not received a dose of this medication, inform your doctor or other healthcare professional immediately.

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

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

If you experience any of these possible severe side effects of Piperacilina/Tazobactam Qilu, seek medical attention immediately:

The severe side effects (with their frequency in parentheses or brackets) of piperacilina/tazobactam are:

• severe skin eruptions (Stevens-Johnson syndrome, bullous dermatitis [unknown frequency], toxic epidermal necrolysis [rare]) that initially appear as pinpoint spots or circular red patches with a blister in the center. Other signs include mouth, throat, nose, limb, and genital ulcers, and conjunctivitis (red and swollen eyes). The eruption can progress to extensive blistering and skin peeling that is potentially fatal.
• potentially fatal severe allergic disease (drug reaction with eosinophilia and systemic symptoms) that can affect the skin and vital organs, such as the kidneys and liver.
• a skin disease (acute generalized exanthematous pustulosis), accompanied by fever, characterized by the appearance of numerous small blisters filled with liquid in large areas of swollen and red skin.
• swelling of the face, lips, tongue, or other parts of the body (unknown frequency).
• shortness of breath, wheezing, or breathing difficulties (unknown frequency).
• severe rash or blisters (rare), itching, or skin eruption (frequent).
• yellowing of the eyes or skin (unknown frequency).
• damage to blood cells (the signs include unexpected shortness of breath, urine that is red or brown [unknown frequency], nasal bleeding [rare], bruises [unknown frequency]), severe decrease in white blood cells [rare].
• acute or persistent diarrhea, accompanied by fever or weakness (rare).

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

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

• diarrhea

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

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

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

• severe decrease in white blood cells (agranulocytosis), nasal bleeding
• severe colon infection, inflammation of the mucous membrane of the mouth
• toxic epidermal necrolysis (skin peeling)

Unknown frequency (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 disintegration or degradation, hematomas, prolonged bleeding time, increase in platelet count, increase in a specific type of white blood cell (eosinophilia)
• allergic reaction and severe allergic reaction
• inflammation of the liver, yellowing of the skin or white of the eyes
• severe allergic reaction 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 liquid in large areas of swollen and red skin, accompanied by fever (acute generalized exanthematous pustulosis), skin eruptions accompanied by blistering (bullous dermatitis)
• renal insufficiency and kidney problems
• a type of lung disease in which a high number of eosinophils (a type of white blood cell) appear in the lungs
• acute disorientation and confusion (delirium)

The treatment with piperacilina has been associated with an increased incidence of fever and rash in patients with cystic fibrosis.

Betalactam antibiotics, including piperacilina/tazobactam, may cause manifestations of encephalopathy (brain damage or disease) and seizures (convulsions).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial after «CAD». The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Reconstituted solution in vial

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

Diluted solution for infusion

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

From a microbiological point of view, the product must be used immediately. If not used immediately, the previous 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.) was performed under controlled and validated sterile conditions.

For single use only. Discard unused solution contents.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of empty containers and medications that are no longer needed. This will help protect the environment.

Piperacillin/Tazobactam Qilu Composition

• The active ingredients are piperacillin and tazobactam.

Each vial contains 2 g of piperacillin (in the form of piperacillin sodium) and 0.25 g of tazobactam (in the form of tazobactam sodium).

Appearance of Piperacillin/Tazobactam Qilu and packaging contents

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

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

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

QILU PHARMA SPAIN S.L.

Paseo de la Castellana 40, 8th floor, 28046 Madrid, Spain

Manufacturer responsible

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 ANALYTICAL SERVICES Hungary 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:

Last review date of this leaflet: 02/2023

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS):http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

Shelf life after reconstitution/dilution

Reconstituted solution in vial

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

From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions of storage 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

Piperacillin/Tazobactam Qilu will be administered by intravenous infusion (butterfly needle for 30 minutes).

The reconstitution and dilution of the medicinal product should be carried out under aseptic conditions. A visual inspection of the reconstituted/diluted solution should be performed to detect any particles in suspension and changes in color before administration. The solution should only be used if it is transparent and free of particles in suspension.

Preparation of the infusion solution

The powder contained in each vial should be reconstituted with the volume of solvent shown in the table below with one of the compatible reconstitution solvents. The solution should be shaken until complete dissolution. With constant agitation, reconstitution usually takes 5-10 minutes (see the information below for more detailed information on its handling).

* Compatible reconstitution solvents:

• Solution for injection of sodium chloride 0.9% (9 mg/ml)
• Water for injection (1)
• Solution for infusion of glucose 5% (50 mg/ml)

(1)The maximum recommended volume of water for injection 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 indicated, its withdrawal with a syringe will provide the declared 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 dilution solvents:

-Solution for injection of sodium chloride 0.9% (9 mg/ml)

-Solution for infusion of glucose 5% (50 mg/ml)

-Solution for injection of dextran 6% (60 mg/ml) in solution of sodium chloride 0.9% (9 mg/ml)

Incompatibilities

Whenever Piperacillin/Tazobactam Qilu is used simultaneously 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 a significant activation of the aminoglycoside.

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

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

Piperacillin/Tazobactam Qilu is not compatible with lactate sodium solution, Ringer acetate solution, Ringer acetate/malate solution, and Hartmann solution, nor for co-administration through a Y-type injection catheter.

Piperacillin/Tazobactam Qilu should not be added to blood derivatives or albumin hydrolysates.

Co-administration with aminoglycosides

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