PIPERACILLIN 2 g/0.25 g Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Piperacillin + Tazobactam Accord 2 g + 0.25 g, powder for solution for infusion
3. Piperacillin + Tazobactam Accord 4 g + 0.5 g, powder for solution for infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
4. What is Piperacillin + Tazobactam Accord and what is it used for
5. Important information before using Piperacillin + Tazobactam Accord
   1. When not to use Piperacillin + Tazobactam Accord
   2. Warnings and precautions
   3. Children
   4. Piperacillin + Tazobactam Accord and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Piperacillin + Tazobactam Accord contains sodium
6. How to use Piperacillin + Tazobactam Accord
   1. Dosage
   2. Adults and adolescents over 12 years
   3. Children aged 2 to 12 years
   4. Patients with kidney disease
   5. Overdose of Piperacillin + Tazobactam Accord
   6. Missing a dose of Piperacillin + Tazobactam Accord
7. Possible side effects
   1. Frequency not known (cannot be estimated from available data):
   2. Reporting side effects
8. How to store Piperacillin + Tazobactam Accord
9. Contents of the packaging and other information
   1. What Piperacillin + Tazobactam Accord contains
   2. What Piperacillin + Tazobactam Accord looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer
   5. This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
   6. Date of last revision of the leaflet:
   7. Instructions for use
   8. Intravenous administration
   9. Incompatibilities

Leaflet accompanying the packaging: information for the user

Piperacillin + Tazobactam Accord 2 g + 0.25 g, powder for solution for infusion

Piperacillin + Tazobactam Accord 4 g + 0.5 g, powder for solution for infusion

Piperacillin + Tazobactam

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Piperacillin + Tazobactam Accord and what is it used for
• 2. Important information before using Piperacillin + Tazobactam Accord
• 3. How to use Piperacillin + Tazobactam Accord
• 4. Possible side effects
• 5. How to store Piperacillin + Tazobactam Accord
• 6. Contents of the packaging and other information

1. What is Piperacillin + Tazobactam Accord and what is it 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 that are resistant to piperacillin from surviving. This means that when piperacillin and tazobactam are given together, more strains of bacteria will be killed. Piperacillin + Tazobactam Accord is used in adults and adolescents to treat bacterial infections of the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdominal cavity, skin, and blood. Piperacillin + Tazobactam Accord may be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). Piperacillin + Tazobactam Accord is used in children aged 2 to 12 years to treat infections in the abdominal cavity, including appendicitis, peritonitis (infection of the fluid and membrane inside the abdominal organs), and cholecystitis (bile duct infection). Piperacillin + Tazobactam Accord can be used to treat bacterial infections in patients with a low white blood cell count (reduced resistance to infections). In some severe infections, the doctor may consider giving Piperacillin + Tazobactam Accord together with other antibiotics.

2. Important information before using Piperacillin + Tazobactam Accord

When not to use Piperacillin + Tazobactam Accord

• If the patient is allergic to piperacillin or tazobactam.
• If the patient is allergic to antibiotics called penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may be allergic to Piperacillin + Tazobactam Accord.

Warnings and precautions

Before starting treatment with Piperacillin + Tazobactam Accord, the patient should discuss with their doctor, pharmacist, or nurse:

• If the patient has allergies. If the patient has multiple allergies, they should make sure to tell their doctor or healthcare professional about them before taking the medicine.
• If the patient has had diarrhea before treatment or if it occurs during or after treatment. The patient should immediately inform their doctor or healthcare professional about this. The patient should not take any medicines for diarrhea without consulting their doctor.
• If the patient has low potassium levels in the blood. It is possible that the doctor will check the patient's kidneys and perform regular blood tests during treatment.
• If the patient has kidney or liver disease, or is undergoing hemodialysis. It is possible that the doctor will check the patient's kidneys and perform regular blood tests during treatment.
• If the patient is taking another antibiotic called vancomycin at the same time as Piperacillin + Tazobactam Accord, as the risk of kidney damage may be increased (see also Piperacillin + Tazobactam Accord and other medicines in this leaflet).
• If the patient is taking certain medicines (called anticoagulants) that prevent blood from clotting too much (see also Piperacillin + Tazobactam Accord and other medicines in this leaflet) or if unexpected bleeding occurs during treatment. The patient should immediately tell their doctor or healthcare professional about this.
• If the patient experiences seizures during treatment. The patient should immediately tell their doctor or healthcare professional about this.
• If the patient thinks they have a new infection or if an existing infection worsens. In this case, the patient should tell their doctor or healthcare professional about it.

There have been reports of a disease in which the immune system produces too many normally healthy white blood cells called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). This condition can be life-threatening if not diagnosed and treated early. If the patient experiences many symptoms such as fever, swollen lymph nodes, feeling weak, dizziness, shortness of breath, bluish discoloration, or skin rash, they should immediately contact their doctor.

Children

Piperacillin + Tazobactam Accord should not be used in children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin + Tazobactam Accord and other medicines

The patient should tell their doctor or healthcare professional about all medicines they are currently taking, have recently taken, or 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). It may prolong the time it takes for piperacillin and tazobactam to be removed from the body.
• Medicines that prevent blood from clotting too much 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 anesthesia, they should inform their doctor about taking this medicine.
• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may prolong the time it takes for methotrexate to be removed from the body.
• Medicines that lower potassium levels in the blood (e.g., diuretics or certain cancer medicines).
• Medicines containing other antibiotics: tobramycin, gentamicin, or vancomycin. If the patient has kidney disease, they should tell their doctor. Taking Piperacillin + Tazobactam Accord and vancomycin together may increase the risk of kidney damage, even if the patient does not have kidney disease.

The patient should tell their doctor or healthcare professional if they are going to have a blood or urine test, as they should inform their doctor or laboratory staff that they are taking Piperacillin + Tazobactam Accord.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or healthcare professional before taking this medicine. The doctor will decide whether Piperacillin + Tazobactam Accord is suitable for the patient. Piperacillin and tazobactam may pass into the baby in the womb or through breast milk. If the patient is breastfeeding, the doctor will decide whether Piperacillin + Tazobactam Accord is suitable for them.

Driving and using machines

Taking Piperacillin + Tazobactam Accord is unlikely to affect the patient's ability to drive or use machines.

Piperacillin + Tazobactam Accord contains sodium

This medicine contains 108 mg of sodium (the main ingredient of common salt) in each vial, which is 5.4% of the maximum recommended daily intake of sodium in the diet for adults. This medicine contains 216 mg of sodium (the main ingredient of common salt) in each vial, which is 10.8% of the maximum recommended daily intake of sodium in the diet for adults. This should be taken into account in patients on a controlled sodium diet.

3. How to use Piperacillin + Tazobactam Accord

This medicine will be given to the patient by a doctor or other healthcare professional through an intravenous infusion (lasting 30 minutes) into one of the patient's veins.

Dosage

The dose of the medicine given to the patient depends on the disease being treated, the patient's age, and any kidney problems they may have.

Adults and adolescents over 12 years

The usual dose is 4 g of piperacillin and 0.5 g of tazobactam, given into one of the patient's veins (directly into the bloodstream) every 6-8 hours.

Children aged 2 to 12 years

For children with infections in the abdominal cavity, the recommended dose is 100 mg of piperacillin and 12.5 mg of tazobactam per kilogram of body weight, given into one of the patient's veins (directly into the bloodstream) every 8 hours. The usual dose for children with a low white blood cell count is 80 mg of piperacillin and 10 mg of tazobactam per kilogram of body weight, given into one of the patient's veins (directly into the bloodstream) every 6 hours. The doctor will calculate the dose of the medicine based on the child's body weight, but each individual dose of Piperacillin + Tazobactam Accord will not exceed 4 g + 0.5 g. The patient will receive Piperacillin + Tazobactam Accord until the infection symptoms have completely resolved (for 5 to 14 days).

Patients with kidney disease

The doctor may recommend reducing the dose of Piperacillin + Tazobactam Accord or the frequency of administration. It is possible that the doctor will perform blood tests to ensure that the correct dose of the medicine is being given, especially if the patient is receiving the medicine for a long time.

Overdose of Piperacillin + Tazobactam Accord

Piperacillin + Tazobactam Accord will be given to the patient by a doctor or other healthcare professional, so it is unlikely that the wrong dose will be given. However, if the patient experiences side effects such as seizures or thinks they have received too much medicine, they should immediately tell their doctor.

Missing a dose of Piperacillin + Tazobactam Accord

If the patient thinks they have missed a dose of Piperacillin + Tazobactam Accord, they should immediately tell their doctor or healthcare professional. If the patient has any further questions about using this medicine, they should ask their doctor or nurse.

4. Possible side effects

Like all medicines, Piperacillin + Tazobactam Accord can cause side effects, although not everybody gets them. If the patient experiences any of the following serious side effects, they should immediately contact their doctor. Serious side effects (frequency not known) of Piperacillin + Tazobactam Accord include:

• severe skin reactions [Stevens-Johnson syndrome, blistering skin rash (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)], initially appearing as reddened patches similar to targets or circular patches, often with centrally located blisters, occurring on the trunk. Additionally, there may be ulcers in the mouth, throat, nose, limbs, genital area, and conjunctivitis (redness and swelling of the eyes). The rash may develop into widespread blisters or skin peeling and can be life-threatening.
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms), which can affect the skin and, more importantly, other organs under the skin, such as the kidneys and liver.
• skin disease (acute generalized exanthematous pustulosis) with accompanying fever, which manifests as numerous small blisters filled with fluid, located on a swollen and reddened large area of 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 rash or hives (uncommon), itching or rash on the skin (common).
• yellowing of the skin or whites of the eyes (frequency not known).
• blood cell damage [symptoms include: unexpected shortness of breath, red or brown urine (frequency not known), nosebleeds (rare), and small bruises (frequency not known)], significant decrease in white blood cell count (rare).
• severe or persistent diarrhea with fever or weakness (rare).

If the patient experiences any of the above side effects or any other side effects not listed in this leaflet, they should tell their doctor or healthcare professional. Very common side effects (may affect more than 1 in 10 people):

• diarrhea

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

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

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

• decreased white blood cell count (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
• decreased potassium levels in the blood, decreased blood sugar levels
• seizures observed in patients taking high doses of the medicine or with kidney problems
• low blood pressure, vein inflammation (feeling of excessive sensitivity to touch or redness of the inflamed area), skin redness
• increased bilirubin levels in the blood
• skin reactions with blisters (blistering skin rash)
• joint and muscle pain
• chills

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

• significant decrease in white blood cell count (agranulocytosis), nosebleeds
• severe intestinal infection, mouth ulceration
• peeling of the outer layer of skin all over the body (toxic epidermal necrolysis)

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

• significant decrease in red blood cell count, white blood cell count, and platelet count (pancytopenia), decreased white blood cell count (neutropenia), decreased red blood cell count due to premature destruction or degradation, small bruises, prolonged bleeding time, increased platelet count, increased eosinophil count
• allergic reaction and severe allergic reaction
• liver inflammation, yellowing of the skin or whites of the eyes
• severe allergic reaction affecting the whole body, with skin and mucous membrane rash, blisters, and other skin lesions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs, such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small blisters filled with fluid, located on a swollen and reddened large area of skin, with fever (acute generalized exanthematous pustulosis), skin reactions with blisters (blistering skin rash)
• kidney damage and kidney disease
• a lung disease in which eosinophils (a type of white blood cell) appear in the lungs in increasing numbers
• acute confusion and disorientation (delirium)

Piperacillin administration has been associated with a higher incidence of fever and rash in patients with cystic fibrosis. Beta-lactam antibiotics, including piperacillin/tazobactam, may cause symptoms of brain dysfunction (encephalopathy) and seizures.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, or to the marketing authorization holder. Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Piperacillin + Tazobactam Accord

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 the month stated. There are no special storage instructions for this medicine. Reconstituted and/or diluted solutions of the medicine should be used immediately. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user. For single use only. Any unused solution should be discarded. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the packaging and other information

What Piperacillin + Tazobactam Accord contains

The active substances of the medicine are piperacillin and tazobactam. Piperacillin + Tazobactam Accord 2 g + 0.25 g Each vial contains 2 g of piperacillin (as piperacillin sodium) and 0.25 g of tazobactam (as tazobactam sodium). Piperacillin + Tazobactam Accord 4 g + 0.5 g Each vial contains 4 g of piperacillin (as piperacillin sodium) and 0.5 g of tazobactam (as tazobactam sodium). The medicine does not contain any other ingredients.

What Piperacillin + Tazobactam Accord looks like and contents of the pack

Piperacillin + Tazobactam Accord 2 g + 0.25 g The medicine is a white or almost white powder for solution for infusion, in a vial. Pack sizes: 1, 10, or 50 vials in a carton. Piperacillin + Tazobactam Accord 4 g + 0.5 g The medicine is a white or almost white powder for solution for infusion, in a vial. Pack sizes: 1, 10, or 50 vials in a carton. Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o. ul. Taśmowa 7 02-677 Warszawa Tel: +48 22 577 28 00

Manufacturer

Mitim S.r.l. Via Giovanni Battista Cacciamali 34-38 25125 Brescia Italy

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

Date of last revision of the leaflet:

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Information intended for healthcare professionals only:

Note: Piperacillin + Tazobactam Accord is not recommended for use in adult patients with bacteraemia caused by ESBL-producing strains of E. coli and K. pneumoniae.

Instructions for use

Piperacillin + Tazobactam Accord should be administered by intravenous infusion (over 30 minutes).

Intravenous administration

The solution should be prepared by adding the appropriate volume of one of the following compatible solvents for reconstitution to the vial. The vial should be shaken until the powder is dissolved. The powder dissolves within 5 to 10 minutes of continuous shaking (detailed information on handling the medicine is given below).

* Compatible solvents for reconstitution:

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

The maximum recommended volume of sterile water for injection is 50 mL per dose. The reconstituted solution should be withdrawn from the vial using a syringe. After reconstitution, the contents of the vial withdrawn using a syringe will contain the amount of piperacillin and tazobactam stated on the label. The solution prepared in this way can be further diluted to the required volume (e.g., 50 mL to 150 mL) with one of the following diluents:

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

Incompatibilities

If Piperacillin + Tazobactam Accord is administered together with other antibiotics (e.g., aminoglycosides), they should be given separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro can cause significant inactivation of the aminoglycoside. Piperacillin + Tazobactam Accord should not be mixed with other medicines in a syringe or infusion bottle, as compatibility has not been established. Due to chemical instability, Piperacillin + Tazobactam Accord should not be used with solutions containing sodium bicarbonate. Ringer's solution with lactates (Hartmann's solution) is incompatible with Piperacillin + Tazobactam Accord. Piperacillin + Tazobactam Accord should not be added to blood products or albumin hydrolysates.