Piperacillin and tazobactam Ibigen

Package leaflet: Information for the user

Piperacillin and Tazobactam Ibigen 2 g/0.25 g and 4 g/0.5 g powder for solution for infusion

Read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Piperacillin and Tazobactam Ibigen is and what it is used for
2. What you need to know before taking Piperacillin and Tazobactam Ibigen
3. How to take Piperacillin and Tazobactam Ibigen
4. Possible side effects
5. How to store Piperacillin and Tazobactam Ibigen
6. Contents of the pack and other information

1. What Piperacillin and Tazobactam Ibigen is and what it is used for

Piperacillin belongs to a group of antibiotic medicines known as "broad-spectrum penicillins", which are able to kill many types of bacteria. Tazobactam can prevent certain bacteria from resisting piperacillin. This means that when piperacillin and tazobactam are administered together, a greater number of bacterial types are eliminated.

Piperacillin and Tazobactam Ibigen is indicated in adults and adolescents for the treatment of bacterial infections affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin, or blood. Piperacillin and Tazobactam Ibigen may be used to treat infections in patients with low white blood cell counts (reduced resistance to infections).

Piperacillin and Tazobactam Ibigen is indicated in children aged between 2 and 12 years for the treatment of abdominal infections such as appendicitis, peritonitis (infection of the fluid and tissue lining the abdominal organs), and gallbladder (biliary) infections.

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

Your doctor may use Piperacillin and Tazobactam Ibigen in combination with other antibiotics for certain severe infections.

2. What you should know before using Piperacillin and Tazobactam Ibigen

Do not use Piperacillin and Tazobactam Ibigen

• If you are allergic to piperacillin or tazobactam
• If you are allergic to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may be allergic to Piperacillin and Tazobactam Ibigen

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Piperacillin and Tazobactam Ibigen:

• If you have allergies. If you have multiple allergies, inform your doctor or healthcare professional before taking this product
• If you have diarrhea before treatment or develop diarrhea during or after treatment. In this case, inform your doctor or healthcare professional immediately. Do not take anti-diarrheal medicines before speaking with your doctor
• If you think your infection is worsening or you develop a new infection. In this case, you must inform your doctor or healthcare professional
• If you are taking another antibiotic called vancomycin concomitantly with Piperacillin and Tazobactam Ibigen, this may increase the risk of kidney problems (see also “Other medicines and Piperacillin and Tazobactam Ibigen” in this leaflet)
• If you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also “Other medicines and Piperacillin and Tazobactam Ibigen” in this leaflet) or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or healthcare professional immediately
• If you have liver or kidney problems, or are undergoing hemodialysis. Your doctor may require kidney function tests before administering this medicine and may request regular blood tests during treatment
• If you experience seizures during treatment. In this case, inform your doctor or healthcare professional
• If you have low levels of potassium in the blood. Your doctor may require kidney function tests before you take this medicine and may request regular blood tests during treatment

Children
The use of piperacillin/tazobactam is not recommended in children under 2 years of age due to insufficient data on safety and efficacy.
Other medicines and Piperacillin and Tazobactam Ibigen
Inform your doctor or healthcare professional if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines may interact with piperacillin and tazobactam.
These include:

• Medicines for gout (probenecid), which may increase the time required to eliminate piperacillin and tazobactam from your body
• Medicines to thin the blood or treat blood clots (e.g., heparin, warfarin, or aspirin)
• Medicines used to relax muscles during surgical procedures. Inform your doctor if you are scheduled to undergo general anesthesia
• Methotrexate (a medicine used to treat certain cancers, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time required to eliminate methotrexate
• Medicines used to reduce potassium levels in the blood (such as diuretic tablets or certain anticancer drugs)
• Medicines containing other antibiotics, such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Concomitant use of Piperacillin and Tazobactam Ibigen and vancomycin may increase the risk of kidney injury, even if you do not have pre-existing kidney problems.

Effects on laboratory tests
Inform your doctor or laboratory staff that you are taking Piperacillin and Tazobactam Ibigen if you are scheduled for blood or urine tests.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or healthcare professional before taking this medicine. Your doctor will decide whether Piperacillin and Tazobactam Ibigen is appropriate for you.
Piperacillin and tazobactam may be passed to the baby during pregnancy or through breast milk. If you are breastfeeding, your doctor will decide whether you may use Piperacillin and Tazobactam Ibigen.
Driving and use of machines
Taking Piperacillin and Tazobactam Ibigen does not appear to affect your ability to drive or operate machinery.
Piperacillin and Tazobactam Ibigen 2g/0.25g contains sodium
This medicine contains 108 mg of sodium (a main component of table salt) per vial. This corresponds to 5.4% of the maximum daily dietary intake recommended for an adult.
Piperacillin and Tazobactam Ibigen 4g/0.5g contains sodium
This medicine contains 216 mg of sodium (a main component of table salt) per vial. This corresponds to 10.8% of the maximum daily dietary intake recommended for an adult.

3. How to use Piperacillin and Tazobactam Ibigen

Your doctor or healthcare professional will administer this medicine to you as an intravenous infusion (over 30 minutes) into one of your veins.
Dosage
The dose of medicine you will receive depends on the condition being treated, your age, and whether you have any kidney problems.
Adults and adolescents over 12 years of age
The usual dose is 4 g/0.5 g piperacillin/tazobactam administered every 6–8 hours intravenously (directly into the blood).
Children aged between 2 and 12 years
The usual dosage in children with abdominal infections is 100 mg/12.5 mg/kg piperacillin/tazobactam administered every 8 hours intravenously (directly into the blood).
The usual dosage in children with low white blood cell count is 80 mg/10 mg/kg piperacillin/tazobactam administered every 6 hours intravenously (directly into the blood).
Your doctor will calculate the dosage based on the child's body weight, but the daily dosage must not exceed 4 g/0.5 g of Piperacillin and Tazobactam Ibigen.
Piperacillin and Tazobactam Ibigen will be administered until signs of infection have completely disappeared (from 5 to 14 days).
Patients with kidney problems
If you have kidney problems, your doctor may need to reduce the dose of Piperacillin and Tazobactam Ibigen or the frequency of administration. Your doctor may also request blood tests to ensure you are receiving the correct dose, especially if you need to take this medicine for a prolonged period.
If you receive more Piperacillin and Tazobactam Ibigen than you should
Since Piperacillin and Tazobactam Ibigen will be administered by your doctor or healthcare professional, it is unlikely that you will receive an overdose. However, if you experience side effects such as seizures, or think you have received too much medicine, inform your doctor immediately.
If a dose of Piperacillin and Tazobactam Ibigen is missed
If you think a dose of Piperacillin and Tazobactam Ibigen has not been administered, inform your doctor or healthcare professional immediately.
If you have any doubts about how to use this medicine, consult your doctor or other healthcare professional.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Consult a doctor immediately if any of the following potentially serious side effects occur.

The serious adverse effects (with frequency indicated in brackets) of Piperacillin and Tazobactam Ibigen are:

• severe skin rashes [Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)], which initially appear as red, target-shaped spots or circular patches, often with central blisters, typically on the trunk. Other signs include mouth, throat, nose, extremities, genital, or conjunctival ulcers (conjunctivitis – red and swollen eyes). The rash may progress to widespread blisters or extensive skin peeling and may be potentially fatal;
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms) that may involve the skin and, particularly, other organs beneath the skin, such as the kidneys and liver (not known);
• a skin condition (acute generalized exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled blisters appearing within large areas of swollen and red skin (not known);
• swelling of the face, lips, tongue, or other parts of the body (not known);
• shortness of breath, wheezing, or breathing difficulties (not known);
• severe skin rash or hives (uncommon), itching or skin rash (common);
• yellowing of the eyes or skin (not known);
• damage to blood cells [signs include: unexplained shortness of breath, red or brown urine (not known), nosebleeds (rare), pinpoint bruising (not known)]; severe reduction in white blood cell count (rare);
• severe or persistent diarrhoea associated with fever or weakness (rare).

If any of the following adverse effects worsen, or if you notice any adverse effects not listed in this leaflet, inform your doctor or another healthcare professional.

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

• diarrhoea

Common adverse effects (may affect up to 1 in 10 people):

• fungal infection (yeast infection);
• reduced platelet count, reduced red blood cells or blood pigment/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, stomach discomfort;
• increased liver enzymes in the blood;
• skin rash, itching;
• abnormal blood tests for kidney function;
• fever, reaction at the injection site.

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

• decreased white blood cell count (leucopenia), prolonged blood clotting time (prolonged prothrombin time);
• decreased potassium levels in the blood, decreased blood sugar levels;
• epileptic seizures (convulsions) observed in patients receiving high doses or with kidney problems;
• low blood pressure, inflammation of veins (felt as tenderness or redness in the affected area), skin redness;
• increased blood levels of a pigment produced during breakdown (bilirubin);
• skin reactions with redness, skin lesions, hives;
• joint and muscle pain;
• chills.

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

• severe reduction in white blood cells (agranulocytosis), nosebleeds;
• severe colon infection, inflammation of the mucous membranes lining the mouth;
• detachment of the upper layer of skin over the entire body (toxic epidermal necrolysis).

Not known (frequency cannot be estimated from available data):

• severe reduction in red blood cells, white blood cells, and platelets (pancytopenia), reduced white blood cells (neutropenia), reduced red blood cells due to premature breakdown or destruction, appearance of bruises with small spots, prolonged bleeding time, increased platelet count, increase in a specific type of white blood cells (eosinophilia);
• allergic reaction and severe allergic reaction;
• inflammation of the liver, yellowish discoloration of the skin or whites of the eyes;
• severe, widespread allergic reaction affecting the entire body with skin and mucosal rash, blisters, and various skin eruptions (Stevens-Johnson syndrome), severe allergic reaction involving the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters appearing within large areas of swollen and red skin accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis);
• impaired kidney function and kidney problems;
• a form of lung disease in which eosinophils (a type of white blood cell) appear in increased numbers in the lungs;
• acute disorientation and confusion (delirium).

Treatment with piperacillin has been associated with an increased incidence of fever and skin rash in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin/tazobactam, may lead to manifestations of encephalopathy and seizures.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor or healthcare professional. You can also report adverse effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Piperacillin and Tazobactam Ibigen

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 vial after “Exp”. The expiry date refers to the last day of that month.
Unopened vial: store at a temperature not exceeding 25°C. Keep in the original packaging.
The reconstituted/diluted solution must be used within 5 hours if stored at 20–25°C and within 24 hours if stored at 2–8°C.
Only clear solutions, free from visible particles, should be used.
For single use only.
Discard any unused solution.
Do not dispose of medicines 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 Other Information

What Piperacillina e Tazobactam Ibigen Contains
The active substances are piperacillin and tazobactam.
Each vial contains 2 g of piperacillin (as sodium salt) and 0.25 g of tazobactam (as sodium salt).
Each vial contains 4 g of piperacillin (as sodium salt) and 0.5 g of tazobactam (as sodium salt).

Description of the Appearance of Piperacillina e Tazobactam Ibigen and Package Contents
White to almost white powder.
Clear glass vial with a rubber stopper, aluminium seal, and flip-off cap.

Packaging
Piperacillina e Tazobactam Ibigen 2 g/0.25 g powder for solution for infusion:
1 x 1 vial containing powder for solution for infusion (DE/H/904/01/DC)
10 x 1 vial containing powder for solution for infusion (DE/H/904/01/DC)
Not all pack sizes may be marketed.

Marketing Authorization Holder
Ibigen S.r.l.
Via Fossignano, 2
04011, Aprilia (LT)
Italy
[email protected]

Manufacturer
Istituto Biochimico Italiano G. Lorenzini S.p.A.
Via Fossignano, 2
04011 Aprilia (LT)
Italy

This medicinal product is authorized in the European Economic Area Member States under the following names:
DE: Piperacillin und Tazobactam Ibisqus 2 g/0.25 g Pulver zur Herstellung einer Infusionslösung
DE: Piperacillin und Tazobactam Ibisqus 4 g/0.5 g Pulver zur Herstellung einer Infusionslösung
UK: Piperacillin/Tazobactam 2 g/0.25 g Powder for Solution for Infusion
UK: Piperacillin/Tazobactam 4 g/0.5 g Powder for Solution for Infusion
CZ: PIPERACILLIN/TAZOBACTAM IBIGEN 2g/0.25g prášek pro přípravu infuzního roztoku
CZ: PIPERACILLIN/TAZOBACTAM IBIGEN 4g/0.5g prášek pro přípravu infuzního roztoku
AT: Piperacillin und Tazobactam Ibigen 2 g/0.25 g Pulver zur Herstellung einer Infusionslösung
AT: Piperacillin und Tazobactam Ibigen 4 g/0.5 g Pulver zur Herstellung einer Infusionslösung

The following information is intended exclusively for doctors or healthcare professionals

Instructions for use

Piperacillin and Tazobactam Ibigen is administered by intravenous infusion (over 30 minutes)

Intravenous infusion
Each vial of Piperacillin and Tazobactam Ibigen 2 g/0.25 g must be reconstituted with the
volume of solvent indicated in the following table, using one of the compatible solvents
for reconstitution. Shake until dissolved. When shaken continuously, reconstitution is
achieved within 5–8 minutes (details for handling are provided below).

*Compatible solvents for reconstitution:

• Sodium chloride 0.9% (9 mg/ml) solution for injection
• Water for injections
• 5% glucose solution

The maximum recommended volume of water for injections is 50 ml.

Reconstituted solutions must be withdrawn from the vial using a syringe. When reconstituted as indicated, the volume withdrawn from the vial with a syringe will correspond to the declared amount of piperacillin and tazobactam stated on the label.
The solution may be further diluted to the desired volume (e.g., 50 ml up to 150 ml) using the following solvents:

• Sodium chloride 0.9% (9 mg/ml) solution for injection
• 5% glucose solution

When prepared under aseptic conditions, chemical and physical in-use stability has been demonstrated for 5 hours at 20–25°C and for 24 hours at 2–8°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user. The solution must be inspected visually for particulate matter and to ensure a clear solution before administration. The solution should be used only if it is clear and free from particles.

Incompatibilities
Whenever Piperacillin and Tazobactam Ibigen is used concomitantly with another antibiotic, particularly an aminoglycoside, the drugs must not be mixed in intravenous solutions or administered simultaneously due to physical incompatibility. Mixing Piperacillin and Tazobactam Ibigen with an aminoglycoside in vitro may result in substantial inactivation of the aminoglycosides.
Piperacillin and Tazobactam Ibigen must not be mixed with other medicinal products in the same syringe or infusion vial, as compatibility has not been established.
Due to chemical instability, Piperacillin and Tazobactam Ibigen must not be used with solutions containing sodium bicarbonate alone.
Piperacillin and Tazobactam Ibigen must not be added to blood derivatives or hydrolyzed protein solutions.
Ringer's lactate solution is incompatible with Piperacillin and Tazobactam Ibigen.