Prospecto: information for the user

Piperacillin/Tazobactam Sula 4 g/0.5 g powder for solution for infusion EFG

Read this prospect carefully before starting to use this medicine because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine 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, pharmacist, or nurse, even if they are not listed in this prospect. See section 4

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

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

3. How to use Piperacillin/Tazobactam Sula

4. Possible adverse effects

5. Storage of Piperacillin/Tazobactam Sula

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.

Do not 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.

Warnings and precautions

Consult your doctor, pharmacist or nurse 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 blood tests periodically 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 blood tests periodically 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 “Other medications and Piperacilina/Tazobactam Sala” in this prospecto).
• if you are using certain medications (called anticoagulants) to prevent excessive blood clotting (see also “Other medications and Piperacilina/Tazobactam Sala” in this prospecto) or if you experience unexpected bleeding during treatment. Inform your doctor or another healthcare professional immediately.
• if you experience seizures during treatment. Inform your doctor or another healthcare professional immediately.
• if you think you have developed a new infection or if your infection has worsened. 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 promptly. If you experience multiple symptoms such as fever, swelling of lymph nodes, feeling weak, feeling dizzy, difficulty breathing, bruises or skin rash, contact your doctor immediately.

Children under 2 years

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

Other medications and Piperacilina/Tazobactam Sala

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication, including 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, heparin, warfarin or acetylsalicylic acid).
• medications used to relax muscles during surgery. Inform your doctor if you are 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, even if you do not 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.

Laboratory test effects

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

Pregnancy and breastfeeding

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 a child, your doctor will decide if Piperacilina/Tazobactam is suitable for you.

Driving and operating machines

No adverse effects on the ability to drive or operate machines are anticipated with the use of Piperacilina/Tazobactam Sala.

Piperacilina/Tazobactam Sala contains sodium

This medication contains 216 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 10.8% 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 for 30 minutes).

The dose of medication that is administered to you will depend on the disease for which you are being treated, your age, and whether or not you have kidney problems.

Dosage

The dose of medication that is administered to you will depend on the disease for which you are being treated, your age, and whether or not you have 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 be administered 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 appropriate 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 be administering 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 the event of an 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, 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 can affect the skin and other major organs such as the kidneys or liver.
• skin disease (acute generalized pustular psoriasis) 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 skin eruption (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(can affect up to 1 in 10 people):

• diarrhea

Common side effects(can 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

Rare side effects(can affect up to 1 in 1,000 people):

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

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 cell (eosinophilia).
• - severe allergic reaction and severe allergic reaction.
• - liver inflammation, yellowing of the skin or white of the 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), acute generalized pustular psoriasis accompanied by fever, consisting of numerous small pustules filled with liquid that appear on large areas of swollen and red skin, skin eruptions with blisters (bullous dermatitis).
• - renal function impairment and kidney 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 cause signs of altered brain function (encephalopathy) and seizures.

Reporting 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: 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 are required.

For single use only. Dispose of any unused solution.

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

Composition of Piperacilina/Tazobactam Solution

The active principles are piperacilina and tazobactam.

Each vial contains 4 g of piperacilina (as sodium salt) and 0.5 g of tazobactam (as sodium salt).

Appearance of the product and contents of the container

Piperacilina/Tazobactam Solution 4 g/0.5 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. Laboratory

C/ Gran Capitán, 10

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing:

Reig Jofré, S.A. Laboratory

Jarama, 111

Toledo 45007

Spain

Last review date of this leaflet:March 2023

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

Piperacilina/Tazobactam will be administered by intravenous infusion (through a drip 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 rotary 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 solution for injection 0.9% (9 mg/ml)
• Sterile water for injection preparations(1)
• Glucose 5%

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

The reconstituted solutions must be extracted from the vial with a syringe. After reconstituting in the manner indicated, the contents of the vial extracted with a syringe will provide the nominal amount of piperacilina 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 solution for injection 0.9% (9 mg/ml)
• Glucose 5%
• Dextran 6% in sodium chloride 0.9%

Incompatibilities

Whenever Piperacilina/Tazobactam is used simultaneously with another antibiotic (for

example, aminoglucosides), these should be administered separately. The mixture of beta-lactam antibiotics with aminoglucosidesin vitromay result in a substantial inactivation of the

aminoglucoside.

Piperacilina/Tazobactam Solution should not be mixed with other substances in a syringe or infusion bag, as its compatibility has not been established.

Due to chemical instability, Piperacilina/Tazobactam Solution should not be used with solutions containing only sodium bicarbonate.

Piperacilina/Tazobactam Solution is not compatible with lactate Ringer solution (sodium chloride compound solution).

Piperacilina/Tazobactam Solution should not be added to blood derivatives or albumin hydrolysates.