Piperacillin and tazobactam Noridem

PACKAGE LEAFLET

Package leaflet: Information for the user

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

piperacillin and tazobactam
Generic medicine
Please read this leaflet carefully before this medicine is administered to you 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 they have the same symptoms as yours, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

Piperacillin belongs to a class of medicines known as "broad-spectrum penicillin antibiotics" and is capable of killing many types of bacteria. Tazobactam can prevent certain resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are administered together, they kill a wider range of bacterial types.
Piperacillin and Tazobactam Noridem is used in adults and adolescents for the treatment of bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin, or bloodstream. Piperacillin and Tazobactam Noridem may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin and Tazobactam Noridem is used 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 Noridem may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain severe infections, the physician may consider using Piperacillin and Tazobactam Noridem in combination with other antibiotics.

2. What you should know before being given Piperacillin and Tazobactam Noridem

Do not use Piperacillin and Tazobactam Noridem

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Piperacillin and Tazobactam Noridem:

• if you have allergies; if you suffer from multiple allergies, make sure to inform your doctor or another healthcare professional before receiving this medicine.
• if you have diarrhoea before starting treatment, or if you develop diarrhoea during or after treatment. In this case, inform your doctor or another healthcare professional immediately. Do not take any anti-diarrhoeal medicines without first consulting your doctor.
• if you have low levels of potassium in your blood. Your doctor may want to check your kidney function before you start taking this medicine and may carry out periodic blood tests during treatment.
• if you have kidney or liver problems or if you are undergoing haemodialysis. Your doctor may want to check your kidney function before you start taking this medicine and may carry out periodic blood tests during treatment.
• if you are taking another antibiotic called vancomycin. Taking Piperacillin and Tazobactam Noridem together with vancomycin may increase the risk of kidney damage (see section “Other medicines and Piperacillin and Tazobactam Noridem”).
• if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see section “Other medicines and Piperacillin and Tazobactam Noridem”) or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or another healthcare professional immediately.
• if you develop seizures during treatment. In this case, you must inform your doctor or another healthcare professional.
• if you suspect you have developed a new infection or if your infection has worsened. In this case, you must inform your doctor or another healthcare professional.

Cases have been reported of a condition in which the immune system produces an abnormally high number of white blood cells called histiocytes and lymphocytes, leading to inflammation (haemophagocytic lymphohistiocytosis). If not diagnosed and treated early, this condition can be life-threatening. If you develop several symptoms such as fever, swollen lymph nodes, feeling weak, mental confusion, shortness of breath, bruising, or skin rash, contact your doctor immediately.

Children
Due to insufficient data on safety and efficacy, the use of Piperacillin and Tazobactam Noridem is not recommended in children under 2 years of age.

Other medicines and Piperacillin and Tazobactam Noridem
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines can interact with piperacillin and tazobactam. These include:

• medicines for gout (probenecid), which may increase the time required for elimination of piperacillin and tazobactam from the body;
• medicines to thin the blood or treat blood clots (e.g. heparin, warfarin, or aspirin);
• medicines used to relax muscles during surgery. Inform your doctor if you are due to undergo general anaesthesia;
• methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time required to eliminate methotrexate from the body;
• medicines that reduce potassium levels in the blood (e.g. diuretic tablets or certain anticancer drugs);
• medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking Piperacillin and Tazobactam Noridem and vancomycin at the same time may increase the risk of kidney damage, even if you do not have existing kidney problems.

Effect on laboratory test results
If you are required to provide a blood or urine sample, inform your doctor or laboratory staff that you are taking Piperacillin and Tazobactam Noridem.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or nurse before taking this medicine. Your doctor will decide whether Piperacillin and Tazobactam Noridem is appropriate for you.
Piperacillin and Tazobactam Noridem may pass to the unborn baby through the placenta or into breast milk. If you are breastfeeding, your doctor will decide whether Piperacillin and Tazobactam Noridem is appropriate for you.

Driving and using machines
Piperacillin and Tazobactam Noridem is not expected to affect your ability to drive or use machinery.

Piperacillin and Tazobactam Noridem contains sodium
The recommended maximum daily dose of this medicine contains 864.8 mg of sodium (the main component of table salt). This corresponds to 43.24% of the maximum daily sodium intake recommended for an adult.
Piperacillin and Tazobactam Noridem 2 g/0.25 g:
Consult your doctor or pharmacist if you need 4 or more vials per day for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.
Piperacillin and Tazobactam Noridem 4 g/0.5 g:
Consult your doctor or pharmacist if you need 2 or more vials per day for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.

3. How Piperacillin and Tazobactam Noridem is administered

Your doctor or another healthcare professional will administer this medicine to you as an infusion
(a 30-minute intravenous infusion) into a vein.
Dosage
The dose of medicine you will receive depends on the condition being treated, your age, and whether you have any kidney problems.
Use in adults and adolescents over 12 years of age
The recommended dose is 4 g/0.5 g of Piperacillin and Tazobactam Noridem administered every 6 to 8 hours intravenously (directly into the bloodstream).
Use in children aged 2 to 12 years
The recommended dose for children with abdominal infections is 100 mg/12.5 mg per kg of body weight of Piperacillin and Tazobactam Noridem administered every 8 hours intravenously (directly into the bloodstream). The recommended dose for children with low white blood cell counts is 80 mg/10 mg per kg of body weight of Piperacillin and Tazobactam Noridem administered every 6 hours intravenously (directly into the bloodstream).
The doctor will calculate the dose based on the child's body weight, but each single dose will not exceed 4 g/0.5 g of Piperacillin and Tazobactam Noridem.
Piperacillin and Tazobactam Noridem will be administered until all signs of infection have completely disappeared (from 5 to 14 days).
Patients with kidney problems
The doctor may need to reduce the dose of Piperacillin and Tazobactam Noridem or adjust the frequency of administration. The doctor may also order blood tests to monitor the appropriateness of the treatment dose, especially if you need to take this medicine for a prolonged period.
If you are given more Piperacillin and Tazobactam Noridem than you should
Since Piperacillin and Tazobactam Noridem will be administered by a doctor or another healthcare professional, it is unlikely that you will receive an incorrect dose. However, if you experience side effects such as seizures, or if you think you have been given too high a dose, inform your doctor immediately.
If a dose of Piperacillin and Tazobactam Noridem is missed
If you think a dose of Piperacillin and Tazobactam Noridem has not been administered, inform your doctor or another healthcare professional immediately.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact a doctor immediately if you experience any of the following potentially serious side effects of Piperacillin and Tazobactam Noridem:
The serious side effects (with frequency indicated in brackets) of Piperacillin and Tazobactam Noridem 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-like spots or circular patches, often with central blisters, on the trunk. Other signs include mouth, throat, nose, extremities, genital ulcers, and conjunctivitis (red and swollen eyes). The skin rash may progress to widespread blistering or peeling of the skin and can potentially be life-threatening;
• severe, potentially fatal allergic condition (drug reaction with eosinophilia and systemic symptoms) which may involve the skin and, particularly, other organs beneath the skin such as the kidneys and liver;
• a skin condition (acute generalized exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled blisters appearing within 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 skin rash or hives (uncommon), itching or skin rash (common);
• yellowing of the eyes or skin (not known);
• damage to blood cells [signs include: unexpected shortness of breath, red or brown urine (not known), nosebleeds (rare), and small bruises (not known)], severe decrease in white blood cells (rare);
• severe or persistent diarrhoea accompanied by fever or weakness (rare).

If any of the following side effects worsen, or if you notice any side effect not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Very common (may affect more than 1 in 10 people):

• diarrhoea

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

• fungal infection (yeast infection);
• decrease in platelets, decrease in red blood cells or blood pigment/hemoglobin, abnormal laboratory test results (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time);
• reduction in proteins 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, injection site reaction.

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

• decrease in white blood cells (leucopenia), prolonged blood clotting time (prolonged prothrombin time);
• decrease in blood potassium, decrease in blood glucose;
• 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), flushed skin;
• increase in a pigment in the blood produced by breakdown (bilirubin);
• skin reactions with redness, skin lesions, hives;
• joint and muscle pain;
• chills.

Rare (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 in the mouth;
• detachment of the upper layer of skin all over the body (toxic epidermal necrolysis).

Not known (frequency cannot be estimated from 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 breakdown or premature destruction, small bruises, prolonged bleeding time, increased platelets, increase in a specific type of white blood cells (eosinophilia);
• allergic reaction and severe allergic reaction;
• liver inflammation, yellowing of the skin or whites of the eyes;
• severe widespread allergic reaction with skin and mucosal rashes, blisters, and various skin eruptions (Stevens-Johnson syndrome), severe allergic condition affecting the skin and other organs such as kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters within large areas of swollen and reddened 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 cells) 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 rashes in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin and tazobactam, may lead to manifestations of signs of impaired brain function (encephalopathy) and seizures.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Piperacillin and Tazobactam Noridem

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.
Intact vials: store below 25 °C.
Reconstituted solution
Chemical and physical in-use stability has been demonstrated for up to 24 hours if the product is stored refrigerated at 2 - 8 °C, when reconstituted with one of the compatible solvents for reconstitution (see section 6).
For single use only. Discard any unused solution.
Diluted solution
The reconstituted and further diluted solution must be used within 24 hours if stored refrigerated at 2-8 °C. The storage times for the reconstituted and further diluted solutions are not considered additive (i.e., the solutions cannot be stored for 24 hours + 24 hours). From a microbiological standpoint, once opened, the product should be used immediately. If not used immediately, the times and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2-8 °C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions.
Do not dispose of any medicine 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 Piperacillin and Tazobactam Noridem contains

• The active substances are sodium piperacillin and sodium tazobactam. Each vial (30 mL capacity) contains 2.085 g of sodium piperacillin, equivalent to 2 g of piperacillin, and 0.268 g of sodium tazobactam, equivalent to 0.25 g of tazobactam.
  Sodium content: 4.7 mmol (108.1 mg) of sodium per vial of powder for solution for infusion.
  Each vial (30 mL capacity) contains 4.17 g of sodium piperacillin, equivalent to 4 g of piperacillin and 0.536 g of sodium tazobactam, equivalent to 0.5 g of tazobactam.
  Sodium content: 9.4 mmol (216.2 mg) of sodium per vial of powder for solution for infusion.

• No other components are present.

Description of the appearance of Piperacillin and Tazobactam Noridem and contents of the pack
Piperacillin and Tazobactam Noridem is a white to off-white crystalline powder. The doctor or nurse will mix it with another solution to be administered as an intravenous infusion.
Each vial of Piperacillin and Tazobactam Noridem contains 2.25 g of medicinal product.
Each vial of Piperacillin and Tazobactam Noridem contains 4.5 g of medicinal product.
Each pack contains 1, 5, 10 or 20 vials (glass containers) of Piperacillin and Tazobactam Noridem.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Noridem Enterprises Limited
Evagorou And Makariou
Mitsi Building 3, Office 115
Nicosia 1065, Cyprus

Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY
National Road Athens–Lamia 21 Km,
14568 Krioneri, Attikis, Greece
T: +30 210 8161802

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Germany:
Piperacillin/Tazobactam Noridem 2 g/0.25 g Powder for solution for infusion
Piperacillin/Tazobactam Noridem 4 g/0.5 g Powder for solution for infusion

Ireland:
Piperacillin/Tazobactam 2g/0.25g powder for solution for infusion
Piperacillin/Tazobactam 4g/0.5g powder for solution for infusion

Sweden:
Piperacillin/Tazobactam Noridem
Piperacillin/Tazobactam Noridem

Austria:
Piperacillin/Tazobactam Noridem 2 g/0.25 g Powder for solution for infusion
Piperacillin/Tazobactam Noridem 4 g/0.5 g Powder for solution for infusion

Poland:
Piperacillin/Tazobactam Noridem
Piperacillin/Tazobactam Noridem

Belgium:
Piperacillin/Tazobactam Noridem 2 g/0.25 g poudre pour solution pour perfusion / Pulver zur Herstellung einer Infusionslösung / poeder voor oplossing voor infusie
Piperacillin/Tazobactam Noridem 4 g/0.5 g poudre pour solution pour perfusion / Pulver zur Herstellung einer Infusionslösung / poeder voor oplossing voor infusie

Czech Republic:
Piperacillin/Tazobactam Noridem
Piperacillin/Tazobactam Noridem

Denmark:
Piperacillin/Tazobactam Noridem
Piperacillin/Tazobactam Noridem

Spain:
Piperacilina/Tazobactam Noridem 2 g/0.25 g polvo para solucion para perfusion EFG
Piperacilina/Tazobactam Noridem 4 g/0.5 g polvo para solucion para perfusion EFG

Finland:
Piperacillin/Tazobactam Noridem 2 g/0.25 g infuusiokuiva-aine, liuosta varten
Piperacillin/Tazobactam Noridem 4 g/0.5 g infuusiokuiva-aine, liuosta varten

France:
PIPERACILLINE/TAZOBACTAM NORIDEM 2 g/0.25 g, poudre pour solution pour perfusion
PIPERACILLINE/TAZOBACTAM NORIDEM 4 g/0.5 g, poudre pour solution pour perfusion

Hungary:
Piperacillin/Tazobactam Noridem 2 g/0.25 g por oldatos infúzióhoz
Piperacillin/Tazobactam Noridem 4 g/0.5 g por oldatos infúzióhoz

Italy:
Piperacillina e Tazobactam Noridem
Piperacillina e Tazobactam Noridem

Norway:
Piperacillin/Tazobactam Noridem
Piperacillin/Tazobactam Noridem

Portugal:
Piperacillina + Tazobactam Noridem
Piperacillina + Tazobactam Noridem

Romania:
Piperacillin/Tazobactam Noridem 2 g/0.25 g pulbere pentru soluţie perfuzabilă
Piperacillin/Tazobactam Noridem 4 g/0.5 g pulbere pentru soluţie perfuzabilă

Slovakia:
Piperacillin/Tazobactam Noridem 2 g/0.25 g prášok na infúzny roztok
Piperacillin/Tazobactam Noridem 4 g/0.5 g prášok na infúzny roztok

The following information is intended for healthcare professionals only.

Instructions for use
Piperacillin and Tazobactam Noridem must be administered by intravenous infusion (an intravenous
drip over 30 minutes).
Intravenous use
Reconstitute each vial with the volume of diluent indicated in the table below, using one of the compatible diluents listed. Shake gently with a rotating motion until dissolved. With continuous rotation, reconstitution usually takes between 5 and 10 minutes (for further information on handling, see below).

*Compatible solvents for reconstitution:

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

The reconstituted solution must be withdrawn from the vial using a syringe. Once reconstituted
according to the instructions, the vial contents withdrawn with the provided syringe will deliver the
amount of piperacillin and tazobactam stated on the label.
Reconstituted solutions may be further diluted to achieve the desired volume (e.g., from 50 mL to 150 mL)
using one of the following compatible solvents:

• 0.9% (9 mg/mL) sodium chloride injection solution
• 5% glucose
• 6% dextran in 0.9% (9 mg/mL) sodium chloride
• sterile water for injection

The maximum recommended volume of sterile water for injection per dose is 50 mL.
Incompatibilities
When Piperacillin and Tazobactam Noridem is used concomitantly with another antibiotic (e.g.,
aminoglycosides), the substances must be administered separately. Mixing beta-lactam antibiotics
with aminoglycosides in vitro may cause substantial inactivation of the aminoglycoside.
Piperacillin and Tazobactam Noridem must not be mixed with other substances in the same syringe
or infusion vial, as compatibility has not been established.
Ringer's lactate solution (Hartmann's solution) is incompatible with Piperacillin and Tazobactam Noridem.
Due to chemical instability, Piperacillin and Tazobactam Noridem must not be used with solutions
containing sodium bicarbonate alone.
Piperacillin and Tazobactam Noridem must not be added to blood products or albumin hydrolysates.
Co-administration of Piperacillin and Tazobactam Noridem with aminoglycosides
Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, it is recommended that
Piperacillin and Tazobactam Noridem and aminoglycosides be administered separately.
When concomitant therapy with aminoglycosides is indicated, Piperacillin and Tazobactam Noridem
and the aminoglycoside must be reconstituted and diluted separately.

• Do not mix or co-administer with aminoglycosides.
• Do not reconstitute or dilute with Ringer's lactate solution (Hartmann's solution).

For single use only. Reconstitution/dilution must be performed under controlled, aseptic, and validated
conditions. Prior to administration, the solution should be inspected visually for particulate matter and
discoloration. The solution should only be used if it is clear and free of particles. Discard any unused
solution. Any unused product or waste material should be disposed of in accordance with local
regulations.
Displacement volume
Piperacillin and Tazobactam 2 g/0.25 g displaces 1.56 mL.
Piperacillin and Tazobactam 4 g/0.5 g displaces 3.12 mL.