Package Insert: Information for the User

Piperacillin/Tazobactam Sodium 2 g/0.25 g Powder for Solution for Infusion EFG

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

• Keep this package insert, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4

1. What is Piperacillin/Tazobactam Sodium and how is it used

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

3. How to use Piperacillin/Tazobactam Sodium

4. Possible adverse effects

5. Storage of Piperacillin/Tazobactam Sodium

6. Contents of the package and additional information

Piperacilina belongs to a group of medicines called "broad-spectrum penicillin antibiotics" and can destroy many types of bacteria. Tazobactam may prevent some resistant bacteria from surviving the effects of piperacilina. By administering piperacilina and tazobactam together, more types of bacteria are destroyed.

Piperacilina/Tazobactam is used in adults and adolescents to treat 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).

Piperacilina/Tazobactam is used in children between 2 and 12 years of age to treat abdominal infections, such as appendicitis, peritonitis (infection of the abdominal fluid and lining), and gallbladder infections. Piperacilina/Tazobactam 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 decide to use Piperacilina/Tazobactam in combination with other antibiotics.

No use Piperacilina/Tazobactam Sala

• If you are allergic to piperacilina or tazobactam or any of the other components of this medication (listed in section 6).
• If you are allergic to antibiotics called penicilinas, cefalosporinas or other inhibitors of the betalactamasas, since you could be allergic to Piperacilina/Tazobactam.

Advertencias y precauciones

Consult your doctor or pharmacist before starting to use Piperacilina/Tazobactam:

• If you have allergies. If you have multiple allergies, make sure to tell your doctor or another healthcare professional before receiving this medication.
• If you had diarrhea before treatment or if you start having it during or after treatment.

Inform your doctor or another healthcare professional immediately. Do not take any medication for diarrhea without consulting your doctor or another healthcare professional first.

• If you have low levels of potassium in your blood. Your doctor may want to examine your kidneys before receiving this medication and may perform periodic blood tests during treatment.
• If you have kidney or liver problems, or if you receive hemodiálisis. Your doctor may want to examine your kidneys before receiving this medication and may perform periodic blood tests during treatment.
• If you are using another antibiotic called vancomicina at the same time as piperacilina/tazobactam, it may increase the risk of kidney damage (see also “Otros medicamentos and Piperacilina/Tazobactam Sala” in this prospecto).
• If you are using certain medications (called anticoagulants) to prevent excessive blood clotting (see also “Otros medicamentos” andPiperacilina/Tazobactam Sala” in this prospecto) 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 during treatment. In this case, you must inform your doctor or another healthcare professional immediately.
• If you think you have developed a new infection or if your infection has worsened. In this case, you must inform your doctor or another healthcare professional immediately.
• Linfohistiocitosis hemofagocítica

Cases of a disease in which the immune system produces too many 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 early. If you experience multiple symptoms such as fever, swelling of the lymph nodes, feeling of weakness, feeling of dizziness, difficulty breathing, bruises or skin rash, contact your doctor immediately.

Niños menores de 2 años

Piperacilina/tazobactam is not recommended for children under 2 years of age due to the scarcity of data on safety and efficacy.

Otros medicamentos and Piperacilina/Tazobactam Sala

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication, even those acquired without a prescription. Some medications may interact with piperacilina or tazobactam.

These include:

• A medication for gout (probenecid). This product may increase the time it takes for piperacilina and tazobactam to be eliminated from the body.
• Medications used to thin the blood or to treat blood clots (for example, heparina, warfarina or ácido acetilsalicílico).
• Medications used to relax muscles during surgery. Inform your doctor if you are going to undergo general anesthesia.
• Metotrexato (a medication used to treat cancer, arthritis or psoriasis). Piperacilina and tazobactam may increase the time it takes for metotrexato to be eliminated from the body.

Medications that decrease the level of potassium in the blood (for example, diuretics or some medications for cancer).

• Medications that contain other antibiotics such as tobramicina, gentamicina or vancomicina.
• Inform your doctor if you have kidney problems.The use of piperacilina/tazobactam and vancomicina at the same time may increase the risk of kidney damage, even if you do not have kidney problems.

Efectos sobre los análisis de laboratorio

If you need to provide a blood or urine sample, inform your doctor or laboratory personnel that you are using Piperacilina/Tazobactam.

Embarazo y lactancia

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication. Your doctor will decide if Piperacilina/Tazobactam is suitable for you.

Piperacilina and tazobactam may pass to the fetus or through breast milk. If you are breastfeeding, your doctor will decide if Piperacilina/Tazobactam is suitable for you.

Conducción and uso de máquinas

No se prevé que el uso de Piperacilina/Tazobactam Sala influya en la capacidad para conducir o

utilizar máquinas.

Piperacilina/Tazobactam Sala contains sodio

This medication contains 108 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 5.4% of the maximum daily sodium intake recommended for an adult. This should be taken into account in patients with low-sodium diets.

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

The dose of medication you receive will depend on the illness you are being treated for, your age, and whether you have any kidney problems.

Dosage

The dose of medication you receive will depend on the illness you are being treated for, your age, and whether you have any kidney problems.

Adults and adolescents 12 years of age or older

The usual dose is 4 g/0.5 g of piperacillin/tazobactam administered every 6-8 hours through a vein (directly into the bloodstream).

Children 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 receive Piperacillin/Tazobactam until the signs of infection have completely disappeared (5 to 14 days).

Patients with kidney problems

Your doctor may need to reduce the dose of Piperacillin/Tazobactam or the frequency of administration. Your doctor may also want to perform blood tests to ensure you receive the correct dose of treatment, especially if you need to use this medication for a long time.

If you use more Piperacillin/Tazobactam than you should

Since a doctor or other healthcare professional will administer Piperacillin/Tazobactam to you, it is unlikely that you will receive an incorrect dose. However, if you experience side effects, such as seizures, or if you are concerned that you may have received more Piperacillin/Tazobactam than you should, consult your doctor or pharmacist immediately.

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

If you forgot to use Piperacilina/Tazobactam

If you think you have not received a dose of Piperacilina/Tazobactam, tell your doctor or other healthcare professional immediately.

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

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

Consult your doctor immediatelyif you experience any of these potentially serious side effects of piperacilina/tazobactam.

Severe side effects(frequency in parentheses)of Piperacilina/Tazobactam are:

• severe skin eruptions [(Stevens-Johnson syndrome, bullous dermatitis (unknown frequency), exfoliative dermatitis (unknown frequency), toxic epidermal necrolysis (rare)] that initially appear on the trunk as red spots with a bull's-eye shape or circular spots with central blisters. Other signs include mouth, throat, nose, limb, genital, and conjunctivitis (red and swollen eyes) ulcers. The eruption may progress to blister formation or generalized skin peeling and, potentially, be fatal.
• potentially fatal severe allergic reaction (medication reaction with eosinophilia and systemic symptoms) that may affect the skin and other major organs such as the kidneys or liver.
• a skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small pustules filled with liquid that appear on 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 difficulty breathing (unknown frequency)
• severe skin eruption or urticaria on the skin (rare), itching or eruption on the skin (frequent)
• yellowing of the eyes and skin (unknown frequency)
• blood cell damage [symptoms include: shortness of breath when not expected, urine that is red or brown (unknown frequency), nasal bleeding (rare), small hematomas (unknown frequency), severe decrease in white blood cells in the blood (rare)]
• severe or persistent diarrhea accompanied by fever or weakness (rare).

If any of the following side effects are severe or if you experience any side effect not mentioned in this leaflet, inform your doctor or another healthcare professional quickly.

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

• diarrhea

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

• yeast infection
• decrease in platelets, decrease in red blood cells or hemoglobin (blood pigment), abnormal laboratory tests (direct Coombs test positive), prolonged blood clotting time (activated partial thromboplastin time prolonged).
• decrease in blood proteins
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach discomfort
• increase in liver enzymes in the blood.
• skin eruptions, itching
• abnormal kidney function tests
• fever, reaction at the injection site

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

• decrease in white blood cells in blood (leucopenia), prolonged blood clotting time (prothrombin time prolonged)decrease in potassium in blood, decrease in blood sugar
• seizures (convulsions), observed in patients receiving high doses or with renal problems
• low blood pressure, inflammation of veins (pain or redness of the affected area), skin redness.
• increase in a breakdown product of blood pigment (bilirubin).
• skin reactions with redness, skin lesions, urticaria
• muscle and joint pain
• chills

Rare side effects(may affect up to 1 in 1000 people):

• severe decrease in white blood cells (agranulocytosis), nasal bleeding
• severe colon infection, inflammation of the mucous membrane of the mouth
• detachment of the top layer of the skin from the entire body (toxic epidermal necrolysis).

Side effects of 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 rupture or degradation, small hematomas, prolonged bleeding time, increase in platelets, 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 eyes.
• severe allergic reaction throughout the body with skin exanthema and mucosa, blisters, and multiple skin eruptions (Stevens-Johnson syndrome), severe allergic reactions affecting the skin and other organs such as the kidneys and liver (medication reaction with eosinophilia and systemic symptoms), numerous small pustules filled with liquid that appear on large areas of swollen and red skin accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis).
• renal function deficiency and renal problems.
• a type of lung disease where eosinophils (a type of white blood cell) appear in the lung in greater numbers.
• acute disorientation and confusion (delirium).

In patients with cystic fibrosis, treatment with piperacilina has been associated with an increased incidence of fever and skin eruptions.

Betalactam antibiotics, including piperacilina/tazobactam, may lead to signs of brain function alteration (encephalopathy) and seizures.

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 not mentioned in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://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 on the vial label

after “CAD”. The expiration date is the last day of the month indicated.

Unopened vials: no special storage conditions required.

For single use only. Dispose of any unused solution.

Medications should not be thrown into the drains or trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Piperacillin/Tazobactam Powder for Solution for Injection

• The active ingredients are piperacillin and tazobactam.

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

Appearance of the product and contents of the container

Piperacillin/Tazobactam Powder for Solution for Injection 2 g/0.25 g is a white or off-white powder that is supplied in a vial.

Container with 1 vial.

Clinical container with 50 vials.

Only some container sizes may be marketed.

Marketing Authorization Holder:

Reig Jofre, S.A.

C/ Gran Capitán, 10

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing:

Reig Jofre, S.A.

Jarama, 111

Toledo 45007

Spain

Last review date of this leaflet:June 2024

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

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This information is intended solely for healthcare professionals:

Instructions for use

Piperacillin/Tazobactam will be administered by intravenous infusion (bottle over 30 minutes).

Intravenous route

It must be reconstituted with the volume of solvent shown in the following table, using one of the compatible solvents for its reconstitution. To facilitate the reconstitution of the vial, invert it and shake it to release the powder adhering to the walls. Shake with rotational movements until it dissolves. If it is shaken constantly, it usually dissolves in 5 to 10 minutes (see details of manipulation below).

* Compatible solvents for reconstitution:

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

(1)The maximum recommended volume of water for injection for each dose is 50 ml.

The reconstituted solutions must be extracted from the vial with a syringe. After reconstituting in the manner indicated, the content of the vial extracted with a syringe will provide the nominal amount of piperacillin and tazobactam.

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

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

Incompatibilities

Whenever Piperacillin/Tazobactam is used simultaneously with another antibiotic (e.g. aminoglycosides), these should be administered separately. The mixture of beta-lactam antibiotics with aminoglycosides in vitro may result in a substantial inactivation of the aminoglycoside.

Piperacillin/Tazobactam Powder for Solution for Injection should not be mixed with other substances in a syringe or infusion bottle, as its compatibility has not been established.

Due to chemical instability, Piperacillin/Tazobactam Powder for Solution for Injection should not be used with solutions that only contain sodium bicarbonate.

Piperacillin/Tazobactam Powder for Solution for Injection is not compatible with lactate Ringer's solution (sodium chloride compound solution).

Piperacillin/Tazobactam Powder for Solution for Injection should not be added to blood derivatives or albumin hydrolysates.