PIPERACILLIN/TAZOBACTAM QILU 2 g/0.25 g POWDER FOR SOLUTION FOR INFUSION

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 medicine 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 having discussed 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 medicine 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 medicine 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 fits) 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

Cases of a disease in which the immune system produces too many white blood cells, which are otherwise normal, called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis), have been reported. 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, feeling of weakness, feeling of 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 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 have 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, inform 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 are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. Your doctor will decide whether the use of piperacillin/tazobactam is suitable for you.

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

Driving and using machines

It is unlikely that the use of this medicine will affect your ability to drive or use machines.

Piperacillin/Tazobactam Qilu contains sodium.

Piperacillin/Tazobactam Qilu 2 g/0.25 g:

This medicine contains 108 mg of sodium (a major component of table salt and kitchen salt) per vial, which is equivalent to 5.4% 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 medicine 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 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 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.

You will be administered this medicine 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 medicine or the frequency at which it is administered. Your doctor may also want to perform blood tests to ensure that the treatment you are receiving is being administered at the correct dose, especially if you need to take this medicine for an extended period.

If you use more Piperacillin/Tazobactam Qilu than you should

Since this medicine 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 fits), or think you have been given too much medicine, 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 medicine and the amount ingested.

If you forget to use Piperacillin/Tazobactam Qilu

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

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

4. Possible side effects

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

If you experience any of the following serious side effects of Piperacillin/Tazobactam Qilu, go to 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, limbs, 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 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 breathing difficulties (frequency not known).
• severe or blistering rash (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 side 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 bleeding time (prolonged activated partial thromboplastin time)
• decrease in blood proteins
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach upset
• 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 clotting 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 palpation 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 hives
• 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 skin and other organs, such as the kidneys and liver, accompanied by skin rash and mucous membranes, 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 increased 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 Medicines Information System: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

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.

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 solvents for reconstitution (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 solvents for dilution to 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 in-use storage times and conditions 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 protect the environment.

6. Contents of the pack and further 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 solution for infusion, 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:

Shelf life 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 solvents for reconstitution (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 solvents for dilution to 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 in-use storage times and conditions 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 should 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 color before administration. The solution should only be used if it is clear and free of particulate matter.

Preparation of the solution for infusion

The powder contained in each vial should be reconstituted with the volume of solvent shown in the following table with one of the compatible solvents for reconstitution. The solution should be shaken until completely dissolved. With constant shaking, reconstitution is usually complete 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 vial contents 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 using Piperacilina/Tazobactam Qilu and other antibiotics (e.g., aminoglycosides) 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 to administer Piperacilina/Tazobactam Qilu and the aminoglycoside separately. When simultaneous treatment with aminoglycosides is indicated, Piperacilina/Tazobactam Qilu and the aminoglycoside should be reconstituted and diluted separately.