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

Introduction

Package Leaflet: Information for the User

Piperacillin/Tazobactam Sala 2 g/0.25 g 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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

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

Piperacillin belongs to a group of medicines called “broad-spectrum penicillin antibiotics” and can kill many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin. In this way, when piperacillin and tazobactam are administered together, more types of bacteria are killed.

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

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

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

Do not use Piperacillin/Tazobactam Sala

• if you are allergic to piperacillin or tazobactam or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to antibiotics called penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may be allergic to Piperacillin/Tazobactam.

Warnings and precautions

Consult your doctor or pharmacist before starting Piperacillin/Tazobactam:

• if you have allergies. If you have multiple allergies, make sure to inform your doctor or other healthcare professional before receiving this medicine.
• if you had diarrhea before treatment or if you start having it 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 consulting your doctor or other healthcare professional first.

if you have low potassium levels in your blood. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment.

• if you have kidney or liver problems, or if you are undergoing hemodialysis. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment.
• if you are using another antibiotic called vancomycin at the same time as piperacillin/tazobactam, it may increase the risk of kidney damage (see also “Other medicines and Piperacillin/Tazobactam Sala” in this leaflet).
• if you are using certain medications (called anticoagulants) to prevent excessive blood clotting (see also “Other medicines and Piperacillin/Tazobactam Sala” in this leaflet) 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 during treatment. In this case, you must inform your doctor or other 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 other healthcare professional immediately.
• 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, feeling of weakness, dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

Children under 2 years

Piperacillin/tazobactam is not recommended for use in children under 2 years of age due to the lack of safety and efficacy data.

Other medicines and Piperacillin/Tazobactam Sala

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. Some medicines may interact with piperacillin or tazobactam.

These include:

• a medicine for gout (probenecid). This product may increase the time it takes for piperacillin and tazobactam to be eliminated from the body.
• medicines used to thin the blood or treat blood clots (e.g., heparin, warfarin, or acetylsalicylic acid).
• medicines used to relax muscles during surgery. Inform your doctor if you are going to undergo general anesthesia.
• methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time it takes for methotrexate to be eliminated from the body.

medicines that decrease potassium levels in the blood (e.g., diuretic pills or certain cancer medications).

• medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin.
• Tell your doctor if you have kidney problems. The use of 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 provide a blood or urine sample, tell your doctor or 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 pharmacist before using this medicine. Your doctor will decide if Piperacillin/Tazobactam is suitable for you.

Piperacillin and tazobactam may pass to the baby in the womb or through breast milk. If you are breastfeeding a child, your doctor will decide if Piperacillin/Tazobactam is suitable for you.

Driving and using machines

It is not expected that the use of Piperacillin/Tazobactam Sala will affect your ability to drive or use machines.

Piperacillin/Tazobactam Sala contains sodium

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

3. How to use Piperacillin/Tazobactam Sala

Your doctor or other healthcare professional will administer this medicine to you by intravenous infusion (in a vein with a drip for 30 minutes).

Dosage

The dose of medicine that you will receive depends on the disease being treated, your age, and whether you have kidney problems.

Adults and adolescents 12 years 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 (from 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 are receiving the correct dose of treatment, especially if you need to use this medicine for a long time.

If you use more Piperacillin/Tazobactam Sala 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, phone 91 562 04 20, indicating the medicine and the amount administered.

If you miss a dose of Piperacillin/Tazobactam

If you think you have missed a dose of Piperacillin/Tazobactam, tell your doctor or other healthcare professional immediately.

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

4. Possible side effects

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

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

Serious side effects (with frequency in parentheses)of Piperacillin/Tazobactam are:

• severe skin rash ((Stevens-Johnson syndrome, bullous dermatitis (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare))that initially appears on the trunk as reddish spots with a target-like shape or circular spots with central blisters. Other signs include ulcers in the mouth, throat, nose, limbs, genitals, and conjunctivitis (red and swollen eyes). The rash can progress to blistering or peeling of the skin and can be potentially fatal.
• severe allergic reaction ((Drug Rash with Eosinophilia and Systemic Symptoms (DRESS))that can affect the skin and other major organs of the body such as the kidneys and liver.
• a skin disease ((Acute Generalized Exanthematous Pustulosis (AGEP))accompanied by fever, consisting of numerous small pus-filled spots that appear on 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 skin rash or hives ((uncommon)), itching or skin rash ((common))
• yellowing of the eyes and skin ((frequency not known))
• blood cell damage ([symptoms include: shortness of breath when not expected, urine that is red or brown (frequency not known), nosebleeds (rare), small bruises (frequency not known), 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 other healthcare professional promptly.

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 (the pigment in blood), abnormal laboratory tests (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time).
• decrease in blood proteins
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach upset
• increase in liver enzymes in the blood
• skin rash, 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 the blood (leukopenia), prolonged blood clotting time (prolonged prothrombin time) decrease in potassium levels in the blood, decrease in blood sugar levels
• seizures (convulsions), observed in patients receiving high doses or with kidney problems
• low blood pressure, inflammation of the veins (pain when touching or redness of the affected area), redness of the skin
• increase in a breakdown product of the blood pigment (bilirubin)
• skin reactions with redness, formation of skin lesions, hives
• muscle and joint pain
• chills

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

• severe decrease in white blood cells (agranulocytosis), nosebleeds
• severe colon infection, inflammation of the mucous membrane of the mouth
• shedding of the top layer of the skin all over the body (toxic epidermal necrolysis)

Side effects with 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 rupture or degradation, small bruises, prolonged bleeding time, increase in platelets, increase in a specific type of white blood cells (eosinophilia)
• allergic reaction and severe allergic reaction
• liver inflammation, yellowing of the skin or the whites of the eyes
• severe allergic reaction all over the body with skin and mucous membrane rashes, blisters, and various skin rashes (Stevens-Johnson syndrome), severe allergic reactions that affect the skin and other organs such as the kidneys and liver (Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)), numerous small pus-filled spots that appear on large areas of swollen and reddened skin accompanied by fever (Acute Generalized Exanthematous Pustulosis (AGEP)), skin reactions with blisters (bullous dermatitis)
• kidney function impairment and kidney problems
• a type of lung disease where eosinophils (a type of white blood cell) appear in the lungs in larger numbers
• acute disorientation and confusion (delirium)

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

Beta-lactam antibiotics, including piperacillin/tazobactam, may cause signs of brain function impairment (encephalopathy) and seizures.

Reporting of side effects:

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

5. Storage of Piperacillin/Tazobactam Sala

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 on the label of the vial after “EXP”. The expiry date is the last day of the month shown.

Unopened vials: no special storage conditions are required.

For single use only. Discard any unused 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. Container Content and Additional Information

Piperacillin/Tazobactam Salt Composition

• 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).

Product Appearance and Container Content

Piperacillin/Tazobactam Salt 2 g/0.25 g is a white or off-white powder supplied in a vial.

Container with 1 vial.

Clinical container with 50 vials.

Only certain container sizes may be marketed.

Marketing Authorization Holder:

Laboratorio Reig Jofre, S.A.

C/ Gran Capitán, 10

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer:

Laboratorio Reig Jofre, S.A.

Jarama, 111

Toledo 45007

Spain

Date of Last Revision of this Leaflet:June 2024

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

--------------------------------------------------------------------------------------------------------------------

This information is intended exclusively for healthcare professionals:

Instructions for Use

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

Intravenous Route

Each vial should be reconstituted with the volume of solvent shown in the following table, using one of the compatible solvents for reconstitution. To facilitate vial reconstitution, invert and shake the vial to release the powder adhering to the walls. Shake with rotary movements until dissolved. If constantly shaken, it usually reconstitutes within 5 to 10 minutes (see handling details below).

• Compatible solvents for reconstitution:
  • Sodium chloride 0.9% injectable solution (9 mg/ml)
  • Sterile water for injectable preparations (1)
  • 5% Glucose

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

The reconstituted solutions should be withdrawn from the vial with a syringe. After reconstitution as indicated, the vial content withdrawn with a syringe will provide the nominal amount of piperacillin and tazobactam.

The reconstituted solutions may 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% injectable solution (9 mg/ml)
• 5% Glucose
• 6% Dextran 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 vitromay result in substantial inactivation of the aminoglycoside.

Piperacillin/Tazobactam Salt 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 Salt should not be used with solutions containing only sodium bicarbonate.

Piperacillin/Tazobactam Salt is not compatible with Ringer's lactate solution (sodium chloride composite solution).

Piperacillin/Tazobactam Salt should not be added to hemoderivatives or albumin hydrolysates.