Piperacillin/tazobactam Sandoz 4 g/0.5 g powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Piperacilina/Tazobactam Sandoz 2 g/0,25 g powder for solution for infusion EFG

Piperacilina/Tazobactam Sandoz 4 g/0,5 g powder for solution for infusion EFG

piperacilina/tazobactam

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Contents of the leaflet :

1. What Piperacilina/Tazobactam Sandoz is and what it is used for
2. What you need to know before using Piperacilina/Tazobactam Sandoz
3. How to use Piperacilina/Tazobactam Sandoz
4. Possible side effects
5. How to store Piperacilina/Tazobactam Sandoz
6. Contents of the pack and other information

1. What Piperacillin/Tazobactam Sandoz is and what it is used for

Piperacillin belongs to a group of medicines called "broad-spectrum penicillin antibiotics" that can destroy many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin. Thus, when piperacillin and tazobactam are administered together, a wider range of bacteria are destroyed.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as flu or the common cold.

It is important that you follow your doctor's instructions regarding dosage, administration, and duration of treatment.

Do not store or reuse this medicine. If you have leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Medicines should not be disposed of via wastewater or household waste.

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

Piperacillin/Tazobactam is used in children between 2 and 12 years of age to treat abdominal infections such as appendicitis, peritonitis (infection of the fluid and lining of abdominal organs), and infections of the gallbladder. Piperacillin/Tazobactam Sandoz 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 decide to use piperacillin/tazobactam in combination with other antibiotics.

2. What you need to know before using Piperacillin/Tazobactam Sandoz

Do not use Piperacillin/Tazobactam Sandoz

• 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 be allergic to piperacillin/tazobactam.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using piperacillin/tazobactam:

• if you have allergies. If you have multiple allergies, make sure to inform your doctor or other healthcare professional before receiving this medicine,
• if you have diarrhoea before treatment or develop diarrhoea during or after treatment. In this case, inform your doctor or other healthcare professional immediately. Do not take any anti-diarrhoeal medication 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 receive this medicine and may carry out periodic blood tests during treatment,
• if you are taking another antibiotic called vancomycin at the same time as piperacillin/tazobactam, as this may increase the risk of kidney damage (see also “Other medicines and Piperacillin/Tazobactam Sandoz” in this leaflet),
• if you have kidney or liver problems, or if you are undergoing haemodialysis. Your doctor may want to check your kidney function before you receive this medicine and may carry out periodic blood tests during treatment,
• if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also “Other medicines and Piperacillin/Tazobactam Sandoz” in this leaflet) or if you experience unexpected bleeding during treatment. In this case, inform your doctor or other healthcare professional immediately,
• if you experience seizures during treatment. In this case, inform your doctor or other healthcare professional immediately,
• if you suspect you have developed a new infection or your existing infection has worsened. In this case, inform your doctor or other healthcare professional immediately.

Haemophagocytic lymphohistiocytosis

Cases of a condition in which the immune system produces excessive numbers of otherwise normal white blood cells called histiocytes and lymphocytes, leading to inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be potentially life-threatening if not diagnosed and treated early. If you experience multiple symptoms such as fever, swollen lymph nodes, feeling weak, dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

Children under 2 years of age

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

Other medicines and Piperacillin/Tazobactam Sandoz

Inform your doctor or other healthcare professional if you are taking, have recently taken, or might need to take 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 medicine 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 undergoing general anaesthesia,
• 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 reduce potassium levels in the blood (e.g., diuretics or certain cancer medicines),
• medicines containing other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Using piperacillin/tazobactam and vancomycin together may increase the risk of kidney damage, even if you do not have pre-existing kidney problems.

Effects on laboratory tests

If you are required to provide a blood or urine sample, inform your doctor or laboratory staff that you are taking piperacillin/tazobactam.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or other healthcare professional before using this medicine. Your doctor will decide whether piperacillin/tazobactam is appropriate for you.

Piperacillin and tazobactam may pass to the unborn child through the placenta or to the infant through breast milk. If you are breastfeeding, your doctor will decide whether piperacillin/tazobactam is suitable for you.

Driving and using machines

Piperacillin/Tazobactam Sandoz is not expected to affect your ability to drive or operate machinery.

Piperacillin/Tazobactam Sandoz 2 g / 0.25 g contains sodium

This medicine contains 109 mg of sodium (a main component of table/cooking salt) per vial. This corresponds to 6% of the maximum daily recommended sodium intake for an adult.

Piperacillin/Tazobactam Sandoz 4 g / 0.5 g contains sodium

This medicine contains 217 mg of sodium (a main component of table/cooking salt) per vial. This corresponds to 11% of the maximum daily recommended sodium intake for an adult.

This should be taken into account in patients on low-sodium diets.

3. How to use Piperacillin/Tazobactam Sandoz

Your doctor or another healthcare professional will administer this medicine as an intravenous infusion (into a vein via an infusion drip over 30 minutes).

Dose

The dose of medicine you will be given depends on the illness being treated, your age, and whether or not you have kidney problems.

Adults and adolescents over 12 years of age

The usual dose is 4 g/0.5 g of piperacillin/tazobactam administered every 6–8 hours intravenously (directly into the bloodstream).

Children aged 2 to 12 years

The usual dose for children with abdominal infections is 100 mg/12.5 mg/kg body weight of piperacillin/tazobactam administered every 8 hours intravenously (directly into the bloodstream). The usual dose for children with low white blood cell counts is 80 mg/10 mg/kg body weight of piperacillin/tazobactam administered every 6 hours intravenously (directly into the bloodstream).

Your doctor will calculate the dose based on the child's body weight, but each individual dose will not exceed 4 g/0.5 g of piperacillin/tazobactam.

Piperacillin/tazobactam will be administered until all signs of infection have completely disappeared (from 5 to 14 days).

Patients with kidney problems

Your doctor may need to reduce your dose of piperacillin/tazobactam or the frequency of administration. Your doctor may also wish to perform blood tests to ensure you are receiving the correct dose, especially if you need to take this medicine for a prolonged period.

If you use more Piperacillin/Tazobactam Sandoz than you should

Since piperacillin/tazobactam will be administered by a doctor or another healthcare professional, it is unlikely that you will receive an incorrect dose. However, if you experience adverse effects such as seizures, or if you think you have been given too much medicine, inform your doctor immediately.

If you have taken more piperacillin/tazobactam than you should, contact your doctor, pharmacist, or call the Toxicology Information Service immediately at telephone: 91 562 04 20, stating the medicine and the amount used.

If you forget to use Piperacillin/Tazobactam Sandoz

If you think a dose of piperacillin/tazobactam has not been administered, inform your doctor or another healthcare professional immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Contact your doctor immediately if you experience any of the following potentially serious adverse effects of piperacillin/tazobactam.

Serious adverse effects (with frequency in parentheses) of piperacillin/tazobactam are:

• severe skin rashes [Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] which initially appear as reddish spots or circular lesions with central blisters on the trunk. Other signs include ulcers in the mouth, throat, nose, limbs, genitals, and conjunctivitis (red and swollen eyes). The rash may progress to blistering or widespread peeling of the skin and, potentially, may be fatal,
• potentially serious allergic reaction (drug reaction with eosinophilia and systemic symptoms) which may affect the skin and other vital organs such as the kidneys or liver (not known),
• a skin disease (generalized acute exanthematous pustulosis) accompanied by fever, consisting of numerous small fluid-filled pustules appearing on large areas of swollen and reddened skin (not known),
• 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 or hives (uncommon), itching or rash on the skin (not known),
• yellowing of the eyes and skin (not known),
• damage to blood cells (symptoms include: unexpected shortness of breath, red or brown urine (not known), nosebleeds (rare), bruising (not known), severe decrease in white blood cells in the blood (rare)),
• severe or persistent diarrhoea accompanied by fever or weakness (rare).

If any of the following adverse effects are severe, or if you experience any adverse effect 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)

• yeast infection,
• decreased platelets, decreased red blood cells or haemoglobin (blood pigment), abnormal laboratory tests (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, stomach discomfort,
• increased liver enzymes in blood,
• skin rashes, itching,
• abnormal kidney blood tests,
• fever, injection site reaction.

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

• decreased white blood cells in blood (leucopenia), prolonged blood clotting time (prolonged prothrombin time),
• decreased potassium in blood, decreased blood sugar,
• seizures, observed in patients receiving high doses or with kidney problems,
• low blood pressure, inflammation of veins (pain on touching or redness of the affected area), redness of the skin,
• increased levels of a breakdown product of blood pigment (bilirubin),
• skin reactions with redness, skin lesion formation, urticaria,
• muscle and joint pain,
• chills.

Rare adverse 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,
• detachment of the upper layer of skin over the entire body (toxic epidermal necrolysis).

Adverse effects of unknown frequency (cannot be estimated from available data)

• severe decrease in red blood cells, white blood cells, and platelets (pancytopenia), decreased white blood cells (neutropenia), decreased red blood cells due to degradation or premature destruction, small bruises, prolonged bleeding time, increased platelets, increased levels of a specific type of white blood cells (eosinophilia),
• allergic reaction and severe allergic reaction,
• inflammation of the liver, yellowing of the skin or whites of the eyes,
• severe systemic allergic reaction with skin and mucosal rashes, blisters, and various skin eruptions (Stevens-Johnson syndrome), severe allergic reactions affecting the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled pustules appearing on large areas of swollen and reddened skin accompanied by fever (generalized acute exanthematous pustulosis), blistering skin reactions (bullous dermatitis),
• impaired kidney function and kidney problems,
• a type of lung disease in which eosinophils (a type of white blood cells) appear in increased numbers in the lungs,
• 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 impaired brain function (encephalopathy) and seizures.

Reporting of adverse effects:

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Piperacillin/Tazobactam Sandoz

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container and label after "EXP". The expiry date refers to the last day of the month indicated.

Unopened vials/bottles:

No special storage conditions are required.

For storage conditions of the medicine after reconstitution and dilution, see at the end of the leaflet "This information is intended for healthcare professionals only".

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 and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Piperacillin/Tazobactam Sandoz

• The active substances are piperacillin and tazobam.

Piperacillin/Tazobactam Sandoz 2 g/0.25 g

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

Piperacillin/Tazobactam Sandoz 4 g/0.5 g

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

• Other components:

This medicinal product contains no excipients other than the active substances.

Appearance of the product and contents of the pack

Piperacillin/Tazobactam Sandoz 2 g/0.25 g is a white or off-white powder for solution for infusion supplied in glass vials.

The vials are packed in cardboard cartons.

Pack sizes: 1, 5, 10, 12 and 50 vials.

Piperacillin/Tazobactam Sandoz 4 g/0.5 g is a white or off-white powder for solution for infusion supplied in glass vials or bottles.

The vials or bottles are packed in cardboard cartons.

Pack sizes: 1, 5, 10, 12 and 50 vials or bottles.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer:

Sandoz GmbH

Biochemiestrasse 10

A-6250 Kundl

Austria

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

Slovakia: Piperacilin comp. Sandoz 4 g/0.5 g prášok na infúzny roztok

France: PIPERACILLINE/TAZOBACTAM SANDOZ 4 g/0.5 g, poudre pour solution pour perfusion

Hungary: Piperacillin/Tazobactam Sandoz 4 g/0.5 g por oldatos infúzióhoz

Ireland: Piperin 2 g/0.25 g Powder for Solution for Infusion

Piperin 4 g/0.5 g Powder for Solution for Infusion

Netherlands: Piperacilline/Tazobactam Sandoz 2 g/0.25 g poeder voor oplossing infusie

Piperacilline/Tazobactam Sandoz 4 g/0.5 g poeder voor oplossing infusie

Sweden: Piperazillin/Tazobactam Sandoz 2 g/0.25 g pulver till injektions-/infusionsvätska, lösning

Piperazillin/Tazobactam Sandoz 4 g/0.5 g pulver till injektions-/infusionsvätska, lösning

Spain: Piperacilina/Tazobactam Sandoz 2 g/0.25 g polvo para solución para perfusión EFG

Piperacilina/Tazobactam Sandoz 4 g/0.5 g polvo para solución para perfusión EFG

Date of the latest revision of this leaflet: January 2023.

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es.

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This information is intended for healthcare professionals only:

Note: Use is not recommended for bacteremia due to E. coli and K. pneumoniae (ceftriaxone non-susceptible) producing extended-spectrum beta-lactamases (ESBLs) in adult patients.

After reconstitution (and dilution)

Chemical and physical in-use stability has been demonstrated for 24 hours at 20–25 °C and for 48 hours at 2–8 °C.

From a microbiological standpoint, once opened, the product should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2–8 °C, unless reconstitution/dilution takes place under validated, controlled aseptic conditions.

Instructions for use

Piperacillin/Tazobactam is to be administered by intravenous infusion (over 30 minutes).

Reconstitution and dilution must be carried out under aseptic 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 from particles.

Intravenous route

Each vial/bottle must be reconstituted with the volume of diluent shown in the table below, using one of the compatible diluents listed for reconstitution. Shake gently with rotary movements until dissolved. With continuous agitation, reconstitution is usually achieved within 3 minutes (see handling details below).

Content of vial/bottle	Volume of solvent* to be added to the vial/bottle
2 g /0.25 g (2 g of piperacillin and 0.25 g of tazobactam)	10 ml
4 g /0.5 g (4 g of piperacillin and 0.5 g of tazobactam)	20 ml

• Compatible solvents for reconstitution:
  • sterile water for injection,
  • 9 mg/ml sodium chloride (0.9%) solution in water for injection,
  • 50 mg/ml glucose (5%) solution in water for injection,
  • 50 mg/ml glucose (5%) solution in 9 mg/ml sodium chloride (0.9%) solution.

Reconstituted solutions should be withdrawn from the vial using a syringe. After reconstitution as indicated, the vial contents withdrawn with a syringe will provide the nominal amount of piperacillin and tazobactam.

Reconstituted solutions may subsequently be diluted to the desired volume (i.e., from 50 ml to 150 ml) with one of the following compatible diluents:

• 9 mg/ml sodium chloride (0.9%) solution in water for injection,
• 50 mg/ml glucose (5%) solution in water for injection,
• 60 mg/ml dextran (degree 40) (6%) in 9 mg/ml sodium chloride (0.9%) solution.

Incompatibilities

Whenever Piperacillin/Tazobactam is used simultaneously with another antibiotic (e.g., aminoglycosides), they must be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in substantial inactivation of the aminoglycoside. However, amikacin and gentamicin have been shown to be compatible in vitro with piperacillin/tazobactam with certain diluents at specific concentrations (see Co-administration with aminoglycosides below).

Piperacillin/Tazobactam Sandoz must not be mixed with other substances in a syringe or infusion bottle, as compatibility has not been established.

Piperacillin/Tazobactam should be administered via a separate infusion set from any other medication unless compatibility has been demonstrated.

Due to chemical instability, Piperacillin/Tazobactam Sandoz must not be used with solutions containing only sodium bicarbonate.

Piperacillin/Tazobactam Sandoz is incompatible with Ringer's Lactate (Hartmann's) solution.

Piperacillin/Tazobactam Sandoz must not be added to blood products or albumin hydrolysates.

Co-administration of piperacillin/tazobactam with aminoglycosides

Due to in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, separate administration of piperacillin/tazobactam and the aminoglycoside is recommended.

Piperacillin/tazobactam and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated.

Under circumstances where co-administration is recommended, piperacillin/tazobactam is compatible for simultaneous co-administration by Y-site infusion only with the following aminoglycosides under the following conditions:

Aminoglycoside	Piperacillin/tazobactam dose	Volume (ml) of piperacillin/tazobactam diluent	Aminoglycoside concentration range* (mg/ml)	Acceptable diluents
Amikacin	2 g / 0.25 g 4 g / 0.5 g	50, 100, 150	1.75 – 7.5	0.9% sodium chloride or 5% dextrose
Gentamicin	2 g / 0.25 g 4 g / 0.5 g	50, 100, 150	0.7 – 3.32	0.9% sodium chloride or 5% dextrose

• The aminoglycoside dose should be based on the patient's body weight, severity of infection (serious or life-threatening), and renal function (creatinine clearance).

The compatibility of piperacillin/tazobactam with other aminoglycosides has not been established. Only the concentrations and diluents for amikacin and gentamicin, in combination with the piperacillin/tazobactam doses indicated in the table above, have been established as compatible for co-administration via Y-site infusion.

Simultaneous administration via Y-site infusion using conditions other than those specified above may result in inactivation of the aminoglycoside by piperacillin/tazobactam.