Piperacillin + tazobactam eugia

Patient Information Leaflet

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
Piperacillinum + Tazobactamum
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet Contents:

1. What Piperacillin + Tazobactam Eugia is and what it is used for
2. What you need to know 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 Piperacillin + Tazobactam Eugia is and what it is 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 from surviving despite piperacillin. This means that when piperacillin and tazobactam are given together, more bacterial strains are 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 infections, skin infections, and blood infections. Piperacillin + Tazobactam Eugia may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin + Tazobactam Eugia is used in children aged 2 to 12 years to treat abdominal infections such as appendicitis, peritonitis (infection of the fluid and membrane inside the abdominal organs), and cholecystitis (gallbladder infection). Piperacillin + Tazobactam Eugia 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 consider administering 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
  components of this medicine (listed in section 6).

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

Warnings and precautions
Before starting treatment with Piperacillin + Tazobactam Eugia, discuss with your doctor,
pharmacist, or nurse:

• If the patient has any allergies. If the patient has multiple allergies, they should ensure they have informed the doctor or other healthcare professional before taking this medicine.
• If the patient has diarrhoea before treatment, or if diarrhoea develops during or after treatment. Inform the doctor or other healthcare professional immediately. Do not take any medicines for diarrhoea without consulting a doctor.
• If the patient has low potassium levels in the blood. The doctor may check kidney function before administering the medicine and may perform regular blood tests during treatment.
• If the patient has kidney or liver disease, or is undergoing haemodialysis. The doctor may check kidney function before administration and may perform regular blood tests during treatment.
• If the patient is taking another antibiotic called vancomycin at the same time as piperacillin with tazobactam, as this may increase the risk of kidney damage (see also Piperacillin + Tazobactam Eugia and other medicines in this leaflet).
• If the patient is taking medicines to prevent excessive blood clotting, known as anticoagulants (see also Piperacillin + Tazobactam Eugia and other medicines in this leaflet), or if unexpected bleeding occurs during treatment. In such cases, inform the doctor or other healthcare professional immediately.
• If the patient experiences seizures during treatment. Inform the doctor or other healthcare professional immediately.
• If the patient suspects they have developed a new infection or an existing infection has worsened. In such cases, inform the doctor or other healthcare professional.

Haemophagocytic lymphohistiocytosis
Cases of a condition have been reported in which the immune system produces excessive numbers of normally functioning white blood cells called histiocytes and lymphocytes, leading to an inflammatory state (haemophagocytic lymphohistiocytosis). This condition may be life-threatening if not diagnosed and treated early. If multiple symptoms occur, such as fever, swollen lymph nodes, feeling weak, dizziness, shortness of breath, cyanosis, or skin rash, contact a doctor immediately.

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
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any 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). This may prolong the elimination of piperacillin and tazobactam 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 undergo general anaesthesia, they should inform the doctor about taking this medicine.
• Methotrexate (a medicine used in cancer, joint inflammation, or psoriasis). Piperacillin and tazobactam may prolong the elimination of methotrexate from the body.
• Medicines that reduce potassium levels in the blood (e.g. diuretics or certain cancer treatments).
• Medicines containing other antibiotics: tobramycin, gentamicin, or vancomycin.
• If the patient has kidney disease, they should inform the doctor. Concurrent use of piperacillin with tazobactam and vancomycin may increase the risk of kidney damage, even if the patient does not have existing kidney problems.

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

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or other healthcare professional before taking this medicine. The treating doctor will decide whether Piperacillin + Tazobactam Eugia is appropriate for her.

Piperacillin and tazobactam may pass to the unborn child or through human milk. If the patient is breastfeeding, the treating doctor will decide whether Piperacillin + Tazobactam Eugia is appropriate for her.

Driving and operating machinery
Piperacillin + Tazobactam Eugia is unlikely to affect the ability to drive or operate machinery.

Piperacillin + Tazobactam Eugia contains sodium

Piperacillin + Tazobactam Eugia, 2 g + 0.25 g
This medicine contains 108 mg of sodium (the main component of table salt) per vial. This corresponds to 5.4% of the maximum recommended daily dietary sodium intake for adults.

Piperacillin + Tazobactam Eugia, 4 g + 0.5 g
This medicine contains 216 mg of sodium (the main component of table salt) per vial. This corresponds to 10.8% of the maximum recommended daily dietary sodium intake for adults.

This should be taken into account if the patient is on a sodium-controlled diet.

3. How to use Piperacillin + Tazobactam Eugia

This medicine will be administered by a doctor or other healthcare professional as an intravenous infusion (lasting 30 minutes).
Dosage
The dose of medicine given to the patient depends on the illness being treated, the patient's age, and any kidney problems the patient may have.
Adults and adolescents aged 12 years or older
The usual dose is 4 g + 0.5 g of piperacillin with tazobactam, administered intravenously (directly into the bloodstream) every 6 to 8 hours.
Children aged 2 to 12 years
For children with intra-abdominal infections, the recommended dose is 100 mg + 12.5 mg of piperacillin with tazobactam per kg of body weight, administered intravenously (directly into the bloodstream) every 8 hours.
The usual dose for children with low white blood cell counts is 80 mg + 10 mg of piperacillin with tazobactam per kg of body weight, administered intravenously (directly into the bloodstream) 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 symptoms of infection have completely resolved (for 5 to 14 days).
Patients with kidney problems
The doctor may recommend reducing the dose of Piperacillin + Tazobactam Eugia or the frequency of administration. The doctor may perform blood tests to ensure the correct dose is being given, especially if the patient is receiving the medicine for a prolonged period.
Use of a higher than recommended dose of Piperacillin + Tazobactam Eugia
Piperacillin + Tazobactam Eugia will be administered by a doctor or other healthcare professional, so incorrect dosing is unlikely. However, if the patient experiences adverse effects such as seizures, or if the patient believes they have received too high a dose, they should immediately inform the doctor.
Missed dose of Piperacillin + Tazobactam Eugia
If the patient believes a dose of Piperacillin + Tazobactam Eugia has been missed, they should immediately inform the doctor or other healthcare professional.
If there are any further doubts regarding the use of this medicine, consult the doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the potentially serious adverse reactions of Piperacillin + Tazobactam Eugia occur, you should immediately contact your doctor.

Serious adverse reactions (with frequencies indicated in parentheses) of Piperacillin + Tazobactam Eugia include:

• severe skin reactions [Stevens-Johnson syndrome, bullous dermatitis (Frequency not known), exfoliative dermatitis (Frequency not known), toxic epidermal necrolysis (Rare)], initially appearing as red spots resembling a target or circular patches, often with centrally located blisters, occurring on the trunk. Additionally, ulceration of the mouth, throat, nose, limbs, genital organs, and conjunctivitis (redness and swelling of the eyes) may occur. The rash may progress to extensive blistering or skin peeling and may be life-threatening.
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms), which may affect the skin and, more importantly, other internal organs such as the kidneys and liver.
• skin disease (acute generalized exanthematous pustulosis) accompanied by fever, manifesting as numerous small fluid-filled pustules located on swollen and red skin.
• swelling of the face, lips, tongue, or other body parts (Frequency not known).
• shortness of breath, wheezing, or difficulty breathing (Frequency not known).
• severe rash or urticaria (Not very common), itching or rash on the skin (Common).
• yellowing of the skin or whites of the eyes (Frequency not known).
• damage to blood cells [symptoms include: unexpected shortness of breath, red or brown discoloration of urine (Frequency not known), nosebleeds (Rare), minor bruising (Frequency not known), significant decrease in white blood cell count (Rare)].
• severe or persistent diarrhoea with fever or weakness (Rare).

If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, you should inform your doctor or other healthcare professional.

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

• diarrhoea

Common (may occur in no more than 1 in 10 people):

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

Not very common (may occur in no more than 1 in 100 people):

• decreased white blood cell count (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
• decreased potassium levels in blood, decreased blood glucose levels
• seizures observed in patients receiving high doses of the medicine or in patients with kidney problems
• low blood pressure, phlebitis (increased sensitivity to touch or redness in the inflamed area), skin redness
• increased levels of breakdown products of blood pigment (bilirubin)
• skin reactions including redness, skin lesions, urticaria
• joint and muscle pain
• chills

Rare (may occur in less than 1 in 1,000 people):

• significant decrease in white blood cell count (agranulocytosis), nosebleeds
• severe inflammation of the large intestine, inflammation of the oral mucosa
• detachment of the outer layer of skin over the entire body (toxic epidermal necrolysis)

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

• significant decrease in red blood cells, white blood cells, and platelets (pancytopenia), decreased white blood cell count (neutropenia), decreased red blood cell count due to premature destruction or degradation, minor bruising, prolonged bleeding time, increased platelet count, increased number of a specific type of white blood cell (eosinophilia)
• allergic reaction and severe allergic reaction
• hepatitis, yellowing of the skin or whites of the eyes
• severe systemic allergic reaction with skin rash and mucous membrane lesions, blisters, and other skin eruptions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs such as kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled pustules located on swollen and red large skin areas accompanied by fever (acute generalized exanthematous pustulosis), blistering skin reactions (bullous dermatitis)
• impaired kidney function and kidney-related problems
• lung disease characterized by increased presence of eosinophils (a type of white blood cell) in the lungs
• acute disorientation and confusion (delirium)

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

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps provide more information on the safety of the medicine.
Adverse reactions can also be reported to the marketing authorization holder.

5. How to store Piperacillin + Tazobactam Eugia

Keep this medicine out of the 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 stated month.
Powder:
Unopened vials: Store below 25°C.
For single use only.
Any unused solution should be discarded.
Reconstituted and diluted solutions of this medicine are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and for 48 hours at 2°C - 8°C.
From a microbiological point of view, reconstituted and diluted solutions should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C - 8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Piperacillin + Tazobactam Eugia contains
The active substances are piperacillin monohydrate and tazobactam.
Each vial contains piperacillin monohydrate (as sodium piperacillin) equivalent to 2 g of piperacillin and tazobactam (as sodium tazobactam) equivalent to 0.25 g of tazobactam.
Each vial contains piperacillin monohydrate (as sodium piperacillin) equivalent to 4 g of piperacillin and tazobactam (as sodium tazobactam) 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, each contained in a cardboard carton with an enclosed package leaflet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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

Information intended exclusively for healthcare professionals:

Warning: The use of this medicinal product is not recommended in adult patients for the treatment of bacteremia caused by E. coli and K. pneumoniae strains (ceftriaxone-resistant) 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 physician must consult the full Summary of Product Characteristics before administering this medicinal product to any patient.
For slow intravenous infusion.

Pharmaceutical incompatibilities with solvents and other medicinal products

• LACTATED RINGER'S SOLUTION (HARTMANN'S SOLUTION) IS PHARMACEUTICALLY INCOMPATIBLE WITH PIPERACILLIN + TAZOBACTAM EUGIA.
• IF PIPERACILLIN + TAZOBACTAM EUGIA IS ADMINISTERED CONCOMITANTLY WITH ANOTHER ANTIBIOTIC (E.G. AMINOGLYCOSIDES), THESE DRUGS SHOULD BE ADMINISTERED SEPARATELY. MIXING PIPERACILLIN + TAZOBACTAM EUGIA
• WITH AN AMINOGLYCOSIDE IN VITRO MAY CAUSE SIGNIFICANT INACTIVATION OF THE AMINOGLYCOSIDE.
• PIPERACILLIN + TAZOBACTAM EUGIA MUST NOT BE MIXED WITH OTHER MEDICINAL PRODUCTS IN THE SAME SYRINGE OR INFUSION BOTTLE, AS COMPATIBILITY HAS NOT BEEN ESTABLISHED.
• DUE TO CHEMICAL INSTABILITY, PIPERACILLIN + TAZOBACTAM EUGIA MUST NOT BE USED WITH SOLUTIONS CONTAINING SODIUM BICARBONATE.
• PIPERACILLIN + TAZOBACTAM EUGIA MUST NOT BE ADDED TO BLOOD PRODUCTS OR ALBUMIN HYDROLYSATES.

INSTRUCTIONS FOR USE, HANDLING, AND DISPOSAL
The medicinal product must be reconstituted and diluted under aseptic conditions. Before administration, the solution should be inspected visually for particulate matter and discoloration.
The solution may be administered only if it is clear and free from visible particles.

Needle insertion into the rubber stopper – instructions:
To avoid coring of the stopper during needle insertion, it is recommended to use a needle with an external diameter less than or equal to 0.8 mm. The needle should be inserted only in the center of the rubber stopper and perpendicularly.

For single use only. Any unused solution must be discarded.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

Sterile diluents for reconstitution:

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

Dilution instructions (for intravenous infusion)
Each vial of Piperacillin + Tazobactam Eugia, 2 g + 0.25 g, should be reconstituted with 10 mL of one of the above diluents.
Each vial of Piperacillin + Tazobactam Eugia, 4 g + 0.5 g, should be reconstituted with 20 mL of one of the above diluents.
Gently swirl the vial until the powder is completely dissolved.

Reconstituted solutions may be further diluted to the desired volume (e.g., 50 mL to 150 mL) within a concentration range of 13.33 + 1.67 mg/mL to 80 + 10 mg/mL using one of the following compatible diluents:

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

SPECIAL PRECAUTIONS FOR STORAGE
Unopened vials: Store below 25°C.
Reconstituted and diluted solutions of the medicinal product are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and for 48 hours at 2°C–8°C.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the responsibility for the storage duration and conditions prior to use lies with the user. Generally, the solution should not be stored for longer than 24 hours at 2°C–8°C, unless reconstitution and dilution were performed under controlled and validated aseptic conditions.