Piperacillin/tazobactam Aurovitas 2 g/0.25 g powder for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Piperacilina/Tazobactam Aurovitas 2 g/0.25 g powder for solution for infusion EFG

Read all of this leaflet carefully before you start taking 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, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if these are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Piperacilin/Tazobactam Aurovitas is and what it is used for

Piperacillin belongs to a group of medicines called "broad-spectrum penicillin antibiotics" and 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 concomitantly, a wider range of bacteria are destroyed.

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

It is important that you follow the instructions regarding dose, dosing interval, and duration of treatment as indicated by your doctor.

Do not store or reuse this medicine. If you have leftover antibiotic after completing the treatment, return it to the pharmacy for proper disposal. Medicines must not be disposed of via the drain or in 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 the abdominal organs), and gallbladder infections. Piperacillin/tazobactam 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 using piperacillin/tazobactam in combination with other antibiotics.

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

Do not use Piperacillin/Tazobactam Aurovitas

• if you are allergic to piperacillin, tazobactam, or 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 starting to use Piperacillin/Tazobactam Aurovitas:

• 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 had diarrhoea before treatment or develop it during or after treatment. In this case, inform your doctor or other healthcare professional immediately. Do not take any medicine for diarrhoea without first consulting your doctor.
• if you have low levels of potassium in your blood. Your doctor may want to examine your kidneys before you receive this medicine and may carry out periodic blood tests during treatment.
• if you have kidney or liver problems, or 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 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 Aurovitas in this leaflet).
• if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also Other medicines and Piperacillin/Tazobactam Aurovitas in this leaflet) or if you experience unexpected bleeding during treatment. In this case, inform your doctor or other healthcare professional immediately.
• if you have seizures during treatment. In this case, inform your doctor or other healthcare professional immediately.
• if you think you have developed a new infection or your 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 fatal 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 Aurovitas

Tell your doctor or pharmacist 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., diuretic tablets 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 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, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will decide whether piperacillin/tazobactam is suitable for you.

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

Driving and using machines

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

Piperacillin/Tazobactam Aurovitas contains sodium

This medicine contains 108 mg of sodium (the main component of table/cooking salt) per vial. This is equivalent to 5.4% 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 Aurovitas

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

Dosage

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

Adults and adolescents aged 12 years and older

The usual dose is 4 g/0.5 g 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.

You will be administered piperacillin/tazobactam 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 carry out blood tests to ensure you are receiving the correct dose, especially if you need to use this medicine for a prolonged period.

If you use more Piperacillin/Tazobactam Aurovitas than you should

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at 91 562 04 20, indicating the medicine and the amount administered.

If you forget to use Piperacillin/Tazobactam Aurovitas

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 nurse.

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 (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)] which initially appear on the trunk as reddish spots resembling targets or circular spots with central blisters. Other signs include mouth, throat, nose, limbs, genital ulcers, and conjunctivitis (red and swollen eyes). The rash may progress to blistering or widespread peeling of the skin and can potentially be fatal.
• potentially life-threatening severe allergic reaction (drug reaction with eosinophilia and systemic symptoms) that may affect the skin and other vital organs such as the kidneys or liver.
• a skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small fluid-filled pustules appearing on large areas of swollen and reddened skin.
• swelling of the face, lips, tongue, or other parts of the body (frequency not known).
• shortness of breath, wheezing, or difficulty breathing (frequency not known).
• severe skin rash or urticaria (uncommon), itching or skin rash (common).
• yellowing of the eyes and skin (frequency not known).
• damage to blood cells [symptoms include: unexpected shortness of breath, red or brown urine (frequency not known), nosebleeds (rare), small bruises (frequency 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)

• fungal infection.
• decrease in platelets, decrease in red blood cells or haemoglobin (blood pigment), abnormal laboratory tests (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time).
• decrease in blood proteins.
• 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)

• decrease in white blood cells in blood (leucopenia), prolonged blood clotting time (prolonged prothrombin time).
• low blood potassium, low 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), skin redness.
• increase in 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 throughout the body (toxic epidermal necrolysis).

Adverse effects with unknown 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 premature rupture or degradation, small bruises, prolonged bleeding time, increased platelets, increase in 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 (acute generalized 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 brain function disturbances (encephalopathy) and seizures.

Reporting of adverse effects

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

5. Storage of Piperacillin/Tazobactam Aurovitas

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 on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Powder:

Unopened vials: Store below 25°C.

For single use only. Discard any unused solution.

Reconstituted/diluted solutions of the medicine are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and for 48 hours at 2–8°C.

From a microbiological standpoint, reconstituted and diluted solutions should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.

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 Aurovitas

• The active substances are piperacillin and tazobactam. Each vial contains 2 g of piperacillin (as the sodium salt) and 0.25 g of tazobactam (as the sodium salt).
• No other components.

Nature of the product and pack contents

White to off-white powder for solution for infusion.

Piperacillin/Tazobactam Aurovitas is available in packs of 1, 10 or 12 vials, packed in cardboard boxes with a package leaflet.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront
Floriana, FRN 1914
Malta

Manufacturer:

APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Aurovitas Spain, S.A.U.
Avda. de Burgos, 16-D
28036 Madrid
Spain

Date of the most recent review of this leaflet: December 2022

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).

This information is intended exclusively for physicians or healthcare professionals:

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

Piperacillin/Tazobactam Aurovitas 2 g/0.25 g powder for solution for infusion EFG

The following text is an excerpt from the Summary of Product Characteristics (SmPC) intended to assist in the administration of Piperacillin/Tazobactam Aurovitas. When determining the suitability of use in a specific patient, the prescribing physician should be familiar with the full SmPC.

For slow intravenous infusion.

Incompatibilities with diluents and other medicinal products

• Ringer Lactate solution (Hartmann's solution) is not compatible with piperacillin/tazobactam.
• When used concomitantly with other antibiotics (e.g., aminoglycosides), piperacillin/tazobactam must be administered separately. Mixing piperacillin/tazobactam with an aminoglycoside in vitro may result in inactivation of the aminoglycoside.
• Piperacillin/tazobactam must not be mixed with other medicinal products in a syringe or infusion glass bottle, as compatibility has not been established.
• Due to chemical instability, piperacillin/tazobactam must not be used in solutions containing sodium bicarbonate.
• Piperacillin/tazobactam must not be added to blood products or albumin hydrolysates.

Instructions for use, handling and disposal

Reconstitution and dilution must be performed 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.

Instructions for inserting the needle into the rubber stopper

To avoid dislodging the stopper when inserting the needle into the rubber stopper, it is recommended to use a needle with an external diameter of ≤ 0.8 mm for reconstitution of the medicinal product.

The needle should be inserted vertically and only in the center of the rubber stopper.

For single use only. Discard any unused solution.

Disposal of unused medicinal product and all materials that have been in contact with it must be carried out in accordance with local regulations.

Sterile diluents for preparing the reconstituted solution

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

Instructions for dilution (for intravenous infusion)

Each vial of piperacillin/tazobactam 2 g/0.25 g must be reconstituted with 10 ml of one of the above diluents.

Shake until complete dissolution is achieved.

The reconstituted solutions may subsequently be further diluted to a concentration range of 13.33/1.67 mg/ml to 80/10 mg/ml using the following diluents:

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

Special storage conditions

Unopened vials: Store below 25°C.

Reconstituted/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 2–8°C.

From a microbiological standpoint, reconstituted and diluted solutions should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, unless reconstitution and dilution have taken place under controlled, validated aseptic conditions.