PIPERACILLIN/TAZOBACTAM ACCORD HEALTHCARE 2 g/0.25 g POWDER FOR SOLUTION FOR INFUSION

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

Do not use Piperacillin/Tazobactam Accord Healthcare

• if you are allergic to piperacillin or tazobactam.
• if you are allergic to antibiotics called penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may be allergic to Piperacillin/Tazobactam Accord Healthcare.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Piperacillin/Tazobactam Accord Healthcare

• If you have allergies. If you have multiple allergies, make sure to inform your doctor or other healthcare professional before receiving this product.
• if you had diarrhea before treatment or if you start to have 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 first.
• If you have low potassium levels in your blood. Your doctor may want to examine your kidneys before you receive this medication 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 medication and may perform periodic blood tests during treatment.
• If you are taking another antibiotic called vancomycin at the same time as Piperacillin/Tazobactam. This may increase the risk of kidney damage (see also “Other medicines and Piperacillin/Tazobactam Accord Healthcare” in this leaflet)
• If you are using certain medications (called anticoagulants) to prevent excessive blood clotting (see also “Other medicines and Piperacillin/Tazobactam Accord Healthcare” 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.

There have been reports of a disease in which the immune system produces too many white blood cells, 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, weakness, dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

ChildrenPiperacillin/Tazobactam is not recommended for use in children under 2 years of age, as there is insufficient data available on safety and efficacy in this population.

Other medicines and Piperacillin/Tazobactam Accord Healthcare

Tell your doctor or healthcare professional 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 lower potassium levels in the blood (e.g., diuretic pills or certain cancer medicines).
• medicines that contain other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking Piperacillin/Tazobactam Accord Healthcare 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 taking Piperacillin/Tazobactam Accord Healthcare.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or healthcare professional before using this medicine.

Your doctor will decide if Piperacillin/Tazobactam is suitable for you.

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

Driving and using machines

Piperacillin/Tazobactam Accord Healthcare is not expected to affect your ability to drive or use machines.

Piperacillin/Tazobactam Accord Healthcare contains sodium

Piperacillin/Tazobactam Accord Healthcare 2 g/0.25 g powder for solution for infusion EFG

This medicine contains 108 mg of sodium (a major 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.

Piperacillin/Tazobactam Accord Healthcare 4 g/0.5 g powder for solution for infusion EFG

This medicine contains 216 mg of sodium (a major component of table salt/cooking salt) in each vial. This is equivalent to 10.8% of the maximum recommended daily intake of sodium for an adult.

This should be taken into account if you are on a low-sodium diet.

3. How to use Piperacillin/Tazobactam Accord Healthcare

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

Dose

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

Adults and adolescents 12 years and older

The recommended 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 recommended 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 Accord Healthcare.

You will be given Piperacillin/Tazobactam Accord Healthcare 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 Accord Healthcare 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 Accord Healthcare than you should:

Since a doctor or other healthcare professional will be administering Piperacillin/Tazobactam Accord Healthcare to you, it is unlikely that you will receive an incorrect dose. However, if you experience side effects, such as seizures, or think you have been given too much medicine, tell your doctor immediately. If you have taken more piperacillin/tazobactam than you should, contact your doctor, pharmacist, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you forget to use Piperacillin/Tazobactam Accord Healthcare

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

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

The serious side effects (with frequency in parentheses) of Piperacillin/Tazobactam Accord Healthcare are:

• severe skin rashes [Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] that initially appear as reddish patches or circular spots with central blisters on the trunk. Other signs include ulcers in the mouth, throat, nose, extremities, genitals, and conjunctivitis (red and swollen eyes). The rash can progress to blistering or peeling of the skin and potentially be fatal.
• potentially serious allergic reaction (drug reaction with eosinophilia and systemic symptoms) 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) accompanied by fever, consisting of numerous small pus-filled bumps that appear on large areas of swollen and reddened skin
• swelling of the face, lips, tongue, or other parts of the body (not known)
• shortness of breath, wheezing, or difficulty breathing (not known)
• severe rash, urticaria (uncommon), itching, or skin rash (common)
• yellowing of the eyes and skin (not known)
• blood cell damage [symptoms include: shortness of breath when not expected, urine that is red or brown in color (not known), nosebleeds (rare), bruising (not known)], severe decrease in white blood cells in the blood (rare)
• persistent or severe diarrhea accompanied by fever or weakness (rare)

If any of the followingside effects is severe or if you experience any side effect not mentioned in this leaflet, inform your doctor or other healthcare professional.

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 blood pigment/hemoglobin, 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 rashes, itching
• abnormal kidney blood 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 with high doses or kidney problems
• low blood pressure, inflammation of the veins (pain when touching or redness of the affected area), skin redness
• increase in a breakdown product of blood pigment (bilirubin)

• skin reactions with redness, formation of skin lesions, and urticaria
• 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 unknown frequency(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 breakdown, small hematoma, 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 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 reaction with eosinophilia and systemic symptoms), numerous small pus-filled bumps that appear on large areas of swollen and reddened skin accompanied by fever (acute generalized exanthematous pustulosis), 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 greater 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 that they are not listed in this leaflet. You can also report side effects 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 Piperacilina/Tazobactam Accord Healthcare

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 “EXP”. The expiry date refers to the last day of the month stated.

This medicine does not require any special storage conditions.

Reconstituted and/or diluted solutions should be used immediately.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

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. Package Contents and Additional Information

Composition of Piperacilina/Tazobactam Accord Healthcare:

Piperacilina/Tazobactam Accord Healthcare 2 g/0.25 g powder for solution for infusion EFG

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

Piperacilina/Tazobactam Accord Healthcare 4 g/0.5 g powder for solution for infusion EFG

Each vial contains 4 g of piperacillin (as piperacillin sodium) and 0.5 g of tazobactam (as tazobactam sodium)

This medicine does not contain any other ingredients.

Appearance and Package Contents

Piperacilina/Tazobactam Accord Healthcare is a white or off-white powder for solution for infusion supplied in a vial.

Package sizes: 1 vial, 10 vials, or 50 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Accord Healthcare S.L.U.

World Trade Center. Moll de Barcelona, s/n, Edifici Est, 6ª planta.

08039, Barcelona (Spain)

Manufacturer:

Mitim, S.R.L.

Via Cacciamali, 34-38

Brescia

25125 – Italy

This medicine is authorised in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Date of last revision of this leaflet:02/2024

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

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This information is intended for healthcare professionals only:

Note: The use for bacteremia due to extended-spectrum beta-lactamase (ESBL)-producing E. coliand K. pneumoniae(ceftriaxone non-susceptible) is not recommended in adult patients.

Instructions for Use

Piperacilina/Tazobactam Accord Healthcare 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 table below, using one of the compatible solvents for reconstitution. Shake with rotary movements until dissolved. If shaken constantly, it is usually reconstituted within 5 to 10 minutes (see handling details below).

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

(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 contents of the vial 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., 50 ml to 150 ml) with one of the following compatible solvents:

• Sodium chloride 9 mg/ml (0.9%) solution for injection
• Sterile water for injectable preparations

Incompatibilities

Whenever Piperacilina/Tazobactam Accord Healthcare is used concurrently with another antibiotic (e.g., aminoglycosides), they should be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitromay result in substantial inactivation of the aminoglycoside.

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

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

Piperacilina/Tazobactam Accord Healthcare is not compatible with Ringer's lactate solution (Hartmann's solution).

Piperacilina/Tazobactam Accord Healthcare should not be added to hemoderivatives or albumin hydrolysates.