PIPERACILLIN 4 g + 0.5 g Powder

Contents of the leaflet

1. Leaflet attached to the packaging: information for the user
2. Piperacillin + Tazobactam Eugia, 2 g + 0.25 g, powder for solution for infusion
3. Piperacillin + Tazobactam Eugia, 4 g + 0.5 g, powder for solution for infusion
   1. You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
4. What is Piperacillin + Tazobactam Eugia and what is it used for
5. Important information before using Piperacillin + Tazobactam Eugia
   1. When not to use Piperacillin + Tazobactam Eugia
   2. Hemophagocytic lymphohistiocytosis
   3. Children
   4. Piperacillin + Tazobactam Eugia and other medicines
   5. Pregnancy, breastfeeding, and fertility
   6. Driving and using machines
   7. Piperacillin + Tazobactam Eugia contains sodium
6. How to use Piperacillin + Tazobactam Eugia
   1. Dosage
   2. Adult patients and adolescents over 12 years old
   3. Children aged 2 to 12 years
   4. Patients with kidney disease
   5. Using a higher dose of Piperacillin + Tazobactam Eugia than recommended
   6. Missing a dose of Piperacillin + Tazobactam Eugia
7. Possible side effects
   1. Reporting side effects
8. How to store Piperacillin + Tazobactam Eugia
9. Contents of the pack and other information
   1. What Piperacillin + Tazobactam Eugia contains
   2. What Piperacillin + Tazobactam Eugia looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder:
   5. Manufacturer/Importer:
   6. Date of last revision of the leaflet: 03/2023
   7. Information intended for healthcare professionals only:
   8. Piperacillin + Tazobactam Eugia, 2 g + 0.25 g
   9. Piperacillin + Tazobactam Eugia, 4 g + 0.5 g powder for solution for infusion
   10. The following information is an excerpt from the Summary of Product Characteristics, prepared to provide guidance on the administration of Piperacillin + Tazobactam Eugia.
   11. The doctor should read the Summary of Product Characteristics before using this medicine in a particular patient.
   12. For slow intravenous infusion.
   13. Incompatibilities with solvents and other medicines
   14. INSTRUCTIONS FOR USE, HANDLING, AND DISPOSAL
   15. Guidelines for dilution (for intravenous infusion)
   16. SPECIAL PRECAUTIONS FOR STORAGE

Leaflet attached to the packaging: information for the user

Piperacillin + Tazobactam Eugia, 2 g + 0.25 g, powder for solution for infusion

Piperacillin + Tazobactam Eugia, 4 g + 0.5 g, powder for solution for infusion

Piperacillin + Tazobactam

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Piperacillin + Tazobactam Eugia and what is it used for
• 2. Important information before using Piperacillin + Tazobactam Eugia
• 3. How to use Piperacillin + Tazobactam Eugia
• 4. Possible side effects
• 5. How to store Piperacillin + Tazobactam Eugia
• 6. Contents of the pack and other information

1. What is Piperacillin + Tazobactam Eugia and what is it used for

Piperacillin belongs to a group of medicines called "broad-spectrum penicillins". It is an antibiotic that kills many types of bacteria. Tazobactam may prevent some bacteria that are not sensitive to piperacillin from surviving. This means that when piperacillin and tazobactam are given together, more strains of bacteria will be killed. Piperacillin + Tazobactam Eugia is used in adults and adolescents to treat bacterial infections such as lower respiratory tract infections (lungs), urinary tract infections (kidneys and bladder), abdominal cavity infections, skin and blood infections. Piperacillin + Tazobactam Eugia can be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). Piperacillin + Tazobactam Eugia is used in children aged 2 to 12 years to treat abdominal cavity infections, such as appendicitis, peritonitis (infection of the fluid and membrane inside the abdominal organs), and cholecystitis (inflammation of the gallbladder). Piperacillin + Tazobactam Eugia can be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). In some severe infections, the doctor may consider giving Piperacillin + Tazobactam Eugia together with other antibiotics.

2. Important information before using Piperacillin + Tazobactam Eugia

When not to use Piperacillin + Tazobactam Eugia

• If the patient is allergic to piperacillin or tazobactam, or to any of the other ingredients of this medicine (listed in section 6).

If the patient is allergic to antibiotics called penicillins, cephalosporins, or to other beta-lactamase inhibitors, as they may be allergic to Piperacillin + Tazobactam Eugia.

• If the patient has allergies. If the patient has several allergies, they should make sure to tell their doctor or other healthcare professional about them before taking the medicine.
• If the patient has diarrhea before treatment or if it occurs during or after treatment. They should immediately inform their doctor or other healthcare professional about it. They should not take any medicines for diarrhea without consulting their doctor.
• If the patient has low potassium levels in the blood. It is possible that before giving the medicine, the doctor will check the kidneys and will perform regular blood tests during treatment.
• If the patient has kidney or liver disease, or is undergoing hemodialysis. It is possible that before giving the medicine, the doctor will check the kidneys and will perform regular blood tests during treatment.
• If the patient is taking another antibiotic called vancomycin at the same time as piperacillin with tazobactam, it may increase the risk of kidney damage (see also Piperacillin + Tazobactam Eugia and other medicinesin this leaflet).
• If the patient is taking medicines that prevent excessive blood clotting, called anticoagulants (see also Piperacillin + Tazobactam Eugia and other medicinesin this leaflet), or if unexpected bleeding occurs during treatment. They should immediately tell their doctor or other healthcare professional about it.
• If the patient experiences seizures during treatment. They should immediately tell their doctor or other healthcare professional about it.
• If the patient thinks they have a new infection or if an existing infection worsens. In this case, they should tell their doctor or other healthcare professional about it.

Hemophagocytic lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many normally harmless white blood cells called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This disease can be life-threatening if not diagnosed and treated early. If multiple symptoms occur, such as fever, lymph node enlargement, weakness, dizziness, shortness of breath, cyanosis, or skin rash, the patient should immediately contact their doctor.

Children

Piperacillin with tazobactam is not recommended for use in children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin + Tazobactam Eugia and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as about medicines they plan to take, including those available without a prescription. Some medicines may interact with piperacillin and tazobactam. These include:

• A medicine used to treat gout (Probenecid). It may prolong the time it takes for piperacillin and tazobactam to be removed from the body.
• Medicines that reduce blood clotting or are used to treat blood clots (e.g., heparin, warfarin, aspirin).
• Medicines used to relax muscles during surgery. If the patient is to be given general anesthesia, they should inform their doctor about taking this medicine.
• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may prolong the time it takes for methotrexate to be removed from the body.
• Medicines that reduce potassium levels in the blood (e.g., diuretics or certain cancer medicines).
• Medicines containing other antibiotics: tobramycin, gentamicin, or vancomycin.
• If the patient has kidney problems, they should tell their doctor. Taking piperacillin with tazobactam and vancomycin at the same time may increase the risk of kidney damage, even if the patient does not have kidney problems.

Effect on laboratory test results
If the patient is to have a blood or urine test, they should tell their doctor or other healthcare professional that they are taking Piperacillin + Tazobactam Eugia.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or other healthcare professional before taking this medicine. The doctor will decide whether Piperacillin + Tazobactam Eugia is suitable for them. Piperacillin and tazobactam may pass into the baby in the womb or through breast milk. If the patient is breastfeeding, the doctor will decide whether Piperacillin + Tazobactam Eugia is suitable for them.

Driving and using machines

Taking Piperacillin + Tazobactam Eugia is unlikely to affect the patient's ability to drive or use machines.

Piperacillin + Tazobactam Eugia contains sodium

Piperacillin + Tazobactam Eugia, 2 g + 0.25 g
The medicine contains 108 mg of sodium (the main component of common salt) per vial. This is equivalent to 5.4% of the maximum recommended daily intake of sodium in the diet for adults.
Piperacillin + Tazobactam Eugia, 4 g + 0.5 g
The medicine contains 216 mg of sodium (the main component of common salt) per vial. This is equivalent to 10.8% of the maximum recommended daily intake of sodium in the diet for adults.
This should be taken into account if the patient is on a controlled sodium diet.

3. How to use Piperacillin + Tazobactam Eugia

This medicine will be given to the patient by a doctor or other healthcare professional by intravenous infusion (lasting 30 minutes).

Dosage

The dose of the medicine given to the patient depends on the disease being treated, the patient's age, and any kidney problems they may have.

Adult patients and adolescents over 12 years old

Usually, a dose of 4 g + 0.5 mg of piperacillin with tazobactam is given intravenously (directly into the blood) every 6-8 hours.

Children aged 2 to 12 years

In children with abdominal cavity infections, the recommended dose is 100 mg + 12.5 mg of piperacillin with tazobactam per kilogram of body weight, given intravenously (directly into the blood) every 8 hours. Usually, the dose given to children with a low white blood cell count is 80 mg + 10 mg of piperacillin with tazobactam per kilogram of body weight, given intravenously (directly into the blood) every 6 hours. The doctor will calculate the dose based on the child's body weight, but each individual dose of Piperacillin + Tazobactam Eugia will not exceed 4 g + 0.5 g. The patient will receive Piperacillin + Tazobactam Eugia until the infection symptoms have completely resolved (for 5 to 14 days).

Patients with kidney disease

The doctor may recommend reducing the dose of Piperacillin + Tazobactam Eugia or the frequency of administration. It is possible that the doctor will perform blood tests to ensure that the correct dose of the medicine is being given, especially if the patient is receiving the medicine for a long time.

Using a higher dose of Piperacillin + Tazobactam Eugia than recommended

Piperacillin + Tazobactam Eugia will be given by a doctor or other healthcare professional, so it is unlikely that the wrong dose will be given. However, if the patient experiences side effects, such as seizures, or thinks they have received too much medicine, they should immediately tell their doctor.

Missing a dose of Piperacillin + Tazobactam Eugia

If the patient thinks they have missed a dose of Piperacillin + Tazobactam Eugia, they should immediately tell their doctor or other healthcare professional. If the patient has any further doubts about using this medicine, they should consult their doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If the patient experiences any of the serious side effects of Piperacillin + Tazobactam Eugia, they should immediately contact their doctor. Serious side effects (frequency in brackets) of Piperacillin + Tazobactam Eugia include:

• severe skin reactions [Stevens-Johnson syndrome, bullous pemphigoid (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)], initially appearing as reddened patches similar to targets or circular patches, often with centrally located blisters, occurring on the torso. Additionally, there may be ulcers of the mouth, throat, nose, limbs, genital areas, and conjunctivitis (redness and swelling of the eyes). The rash may develop into widespread blisters or peeling of the skin and can be life-threatening.
• a severe, potentially life-threatening allergic reaction (drug rash with eosinophilia and systemic symptoms), which can affect the skin and, more importantly, other organs under the skin, such as the kidneys and liver.
• a skin disease (acute generalized exanthematous pustulosis) with accompanying fever, which manifests as numerous small blisters filled with fluid, located on a swollen and reddened large area of skin.

swelling of the face, lips, tongue, or other parts of the body (frequency not known). wheezing, whistling breathing, or difficulty breathing (frequency not known). severe rash or hives (uncommon), itching or rash on the skin (common). yellowing of the skin or whites of the eyes (frequency not known). blood cell damage [symptoms include: unexpected shortness of breath, red or brown urine (frequency not known), nosebleeds (rare), and minor bruising (frequency not known), significant reduction in white blood cell count (rare)]. severe or persistent diarrhea with fever or weakness (rare).

• diarrhea

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

• infections with yeasts
• reduced platelet count, reduced red blood cell count or hemoglobin, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time)
• reduced protein levels in the blood
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, indigestion
• increased liver enzyme activity in the blood
• skin rash, itching
• abnormal kidney function test results
• fever, reaction at the injection site

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

• reduced white blood cell count (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
• reduced potassium levels in the blood, reduced blood sugar levels
• seizures observed in patients taking high doses of the medicine or with kidney problems
• low blood pressure, vein inflammation (sensitivity to touch or redness of the inflamed area), skin redness
• increased bilirubin levels in the blood
• skin reactions with blisters (bullous pemphigoid)
• joint and muscle pain
• chills

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

• significant reduction in white blood cell count (agranulocytosis), nosebleeds
• severe colitis, mouth ulcers
• shedding of the outer layer of the skin all over the body (toxic epidermal necrolysis)

Frequency not known(frequency cannot be estimated from the available data):

• significant reduction in red blood cell count, white blood cell count, and platelet count (pancytopenia), reduction in white blood cell count (neutropenia), reduction in red blood cell count due to premature destruction or degradation, minor bruising, prolonged bleeding time, increased platelet count, increased eosinophil count
• allergic reaction and severe allergic reaction
• liver inflammation, yellowing of the skin or whites of the eyes
• severe allergic reaction affecting the whole body, with skin and mucous membrane rash, blisters, and other skin lesions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs, such as the kidneys and liver (drug rash with eosinophilia and systemic symptoms), numerous small blisters filled with fluid located on a swollen and reddened large area of skin with fever (acute generalized exanthematous pustulosis), blistering skin reactions (bullous pemphigoid)
• kidney problems and impaired kidney function
• a lung disease in which eosinophils (a type of white blood cell) appear in the lungs in increased numbers
• acute confusion and disorientation (delirium)

Administration of piperacillin has been associated with an increased incidence of fever and rash in patients with cystic fibrosis. Beta-lactam antibiotics, including piperacillin with tazobactam, may cause symptoms of brain function disorders (encephalopathy) and seizures.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. By reporting side effects, more information can be collected on the safety of the medicine. Side effects can also be reported to the marketing authorization holder.

5. How to store Piperacillin + Tazobactam Eugia

The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vials after EXP. The expiry date refers to the last day of the month stated. Powder: Unopened vials: Store in a temperature below 25°C. For single use only. Unused solution should be discarded. Reconstituted and diluted solutions of the medicine are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and 48 hours at 2°C - 8°C. From a microbiological point of view, the reconstituted and diluted solutions should be used immediately. If not used immediately, the user is responsible for the storage conditions prior to use, and normally the solution should not be stored for more than 24 hours at 2°C - 8°C, unless the reconstitution and dilution of the medicine took place in controlled and validated aseptic conditions. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Piperacillin + Tazobactam Eugia contains

The active substances of the medicine are piperacillin sodium and tazobactam sodium. Each vial contains piperacillin sodium equivalent to 2 g of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam. Each vial contains piperacillin sodium equivalent to 4 g of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam. The medicine does not contain any other ingredients.

What Piperacillin + Tazobactam Eugia looks like and contents of the pack

Powder for solution for infusion. White or almost white powder. Piperacillin + Tazobactam Eugia is available in packs of 1, 5, and 10 vials, enclosed in a cardboard box with a leaflet. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Eugia Pharma (Malta) Ltd. Vault 14, level 2 Valletta Waterfront Floriana, FRN1914 Malta e-mail: [email protected]

Manufacturer/Importer:

APL Swift Services (Malta) Ltd. HF26, Hal Far Industrial Estate, Hal Far Birzebbugia, BBG 3000 Malta Generis Farmacêutica, S.A. Rua João de Deus 19, Venda Nova 2700-487 Amadora Portugal Arrow Génériques 26 Avenue Tony Garnier 69007 Lyon France

Date of last revision of the leaflet: 03/2023

Information intended for healthcare professionals only:

Note: It is not recommended to use in adult patients for the treatment of bacteremia caused by E. coliand K. pneumoniae(resistant to ceftriaxone) producing extended-spectrum beta-lactamases (ESBL).

Piperacillin + Tazobactam Eugia, 2 g + 0.25 g

Piperacillin + Tazobactam Eugia, 4 g + 0.5 g powder for solution for infusion

The following information is an excerpt from the Summary of Product Characteristics, prepared to provide guidance on the administration of Piperacillin + Tazobactam Eugia.

The doctor should read the Summary of Product Characteristics before using this medicine in a particular patient.

For slow intravenous infusion.

Incompatibilities with solvents and other medicines

• RINGERS SOLUTION WITH LACTATE (HARTMANN SOLUTION) IS INCOMPATIBLE WITH PIPERACILLIN + TAZOBACTAM EUGIA.
• IF PIPERACILLIN + TAZOBACTAM EUGIA IS GIVEN AT THE SAME TIME AS ANOTHER ANTIBIOTIC (SUCH AS AMINOGLYCOSIDES), THESE MEDICINES SHOULD BE GIVEN SEPARATELY. MIXING PIPERACILLIN + TAZOBACTAM EUGIA
• WITH AN AMINOGLYCOSIDE IN VITROMAY CAUSE SIGNIFICANT INACTIVATION OF THE AMINOGLYCOSIDE.
• PIPACILLIN + TAZOBACTAM EUGIA SHOULD NOT BE MIXED WITH OTHER MEDICINES IN A SYRINGE OR INFUSION BOTTLE, AS COMPATIBILITY HAS NOT BEEN ESTABLISHED.
• DUE TO CHEMICAL INSTABILITY, PIPERACILLIN + TAZOBACTAM EUGIA SHOULD NOT BE USED WITH SOLUTIONS CONTAINING SODIUM BICARBONATE.
• PIPACILLIN + TAZOBACTAM EUGIA SHOULD NOT BE ADDED TO BLOOD PRODUCTS OR ALBUMIN HYDROLYSATES.

INSTRUCTIONS FOR USE, HANDLING, AND DISPOSAL

The medicine should be reconstituted and diluted with aseptic precautions. Before administration, the solution should be inspected for visible particles and changes in color. The solution should only be administered if it is clear and free of visible particles. Instructions for inserting the needle into the rubber stopper: To avoid the core phenomenon, when reconstituting the product, it is recommended to use a needle with an outer diameter of less than or equal to 0.8 mm. The needle should be inserted only in the center of the rubber stopper, in a vertical direction. For single use only. Unused solution should be discarded. Any unused medicinal product or waste material should be disposed of in accordance with local regulations. Sterile diluents for preparing the solution after reconstitution:

• Sterile water for injection
• 9 mg/mL (0.9%) sodium chloride injection
• 50 mg/mL (5%) glucose solution in water

Guidelines for dilution (for intravenous infusion)

Each vial of Piperacillin + Tazobactam Eugia, 2 g + 0.25 g, should be dissolved in 10 mL of the above diluents. Each vial of Piperacillin + Tazobactam Eugia, 4 g + 0.5 g, should be dissolved in 20 mL of the above diluents. The vial should be shaken until the solution is dissolved. The reconstituted solutions can be further diluted to the desired volume (e.g., 50 mL to 150 mL) within the concentration range of 13.33 + 1.67 mg/mL to 80 + 10 mg/mL with one of the following compatible solvents:

• 9 mg/mL (0.9%) sodium chloride injection
• 50 mg/mL (5%) glucose solution in water

SPECIAL PRECAUTIONS FOR STORAGE

Unopened vials: Store in a temperature below 25°C. Reconstituted and diluted solutions of the medicine are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and 48 hours at 2°C - 8°C. From a microbiological point of view, the medicinal product should be used immediately. If the medicinal product is not used immediately, the user is responsible for the storage conditions prior to use. Normally, the solution should not be stored for more than 24 hours at 2°C - 8°C, unless the reconstitution and dilution of the medicinal product took place in controlled and validated aseptic conditions.