Piperacillin + tazobactam accord

Package leaflet: 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
Piperacillinum + Tazobactamum
Please read this leaflet carefully before 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 further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Piperacillin + Tazobactam Accord is and what it is 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 pack and other information

1. What Piperacillin + Tazobactam Accord is and what it is 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 resistant to piperacillin from surviving. This means that when piperacillin and tazobactam are given together, more bacterial strains are 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 low white blood cell counts (reduced resistance to infections).
Piperacillin + Tazobactam Accord is used in children aged 2 to 12 years to treat infections of the abdominal cavity, including appendicitis, peritonitis (infection of fluid and membrane lining the abdominal organs), and cholecystitis (gallbladder or biliary tract infection). Piperacillin + Tazobactam Accord 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 administering 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 has allergies to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as they may also be allergic to Piperacillin + Tazobactam Accord.

Warnings and precautions
Before starting treatment with Piperacillin + Tazobactam Accord, discuss with the doctor,
pharmacist, or nurse:

• If the patient has any allergies. If the patient has multiple allergies, they should ensure they have informed the doctor or healthcare professional before taking the medicine.
• If the patient has diarrhoea before treatment, or if it occurs during or after treatment. This should be reported immediately to the doctor or healthcare professional. Do not take any anti-diarrhoeal medicines without consulting a doctor.
• If the patient has low blood potassium levels. The doctor may check kidney function before administering the medicine and perform regular blood tests during treatment.
• If the patient has kidney or liver problems, or is undergoing haemodialysis. The doctor may check kidney function before administration and perform regular blood tests during treatment.
• If the patient is taking another antibiotic called vancomycin at the same time as Piperacillin + Tazobactam Accord, 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) to prevent excessive blood clotting (see also Piperacillin + Tazobactam Accord and other medicines in this leaflet) or if unexpected bleeding occurs during treatment. In such cases, inform the doctor or healthcare professional immediately.
• If the patient experiences seizures during treatment. Inform the doctor or healthcare professional immediately.
• If the patient suspects a new infection has developed or an existing infection has worsened. In such cases, inform the doctor or healthcare professional.

Cases of a condition have been reported in which the immune system produces excessive numbers of normally functioning white blood cells called histiocytes and lymphocytes, leading to an inflammatory state (hemophagocytic lymphohistiocytosis). This condition may be life-threatening if not diagnosed and treated early. If multiple symptoms such as fever, swollen lymph nodes, feeling of weakness, dizziness, shortness of breath, cyanosis, or skin rash occur, contact a doctor immediately.

Children
Piperacillin with tazobactam is not recommended for children under 2 years of age due to insufficient data on safety and efficacy.

Piperacillin + Tazobactam Accord and other medicines
Inform the doctor or healthcare professional about all medicines currently taken or recently taken, as well as any medicines the patient plans to take, including those available without a prescription. Some medicines may interact with piperacillin and tazobactam.
These include, among others:

• A medicine used to treat gout (probenecid). It may prolong the elimination of piperacillin and tazobactam from the body.
• Medicines that reduce blood clotting 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 anaesthesia, inform the doctor about taking this medicine.
• Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may prolong the elimination of methotrexate from the body.
• Medicines that reduce 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 problems, inform the doctor. Concurrent use of Piperacillin + Tazobactam Accord and vancomycin may increase the risk of kidney damage, even if the patient does not have pre-existing kidney disease.

Effect on laboratory test results
If the patient is to provide a blood or urine sample, they should inform the doctor or laboratory staff that they are taking Piperacillin + Tazobactam Accord.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or healthcare professional before taking this medicine.
The treating doctor will decide whether Piperacillin + Tazobactam Accord is appropriate for her.
Piperacillin and tazobactam may pass to the unborn child or through human milk. If the patient is breastfeeding, the treating doctor will decide whether Piperacillin + Tazobactam Accord is appropriate for her.

Driving and operating machinery
Piperacillin + Tazobactam Accord is unlikely to affect the ability to drive or operate machinery.

Piperacillin + Tazobactam Accord contains sodium
This medicine contains 108 mg of sodium (the main component of table salt) per vial. This corresponds to 5.4% of the maximum recommended daily dietary sodium intake for adults.
This medicine contains 216 mg of sodium (the main component of table salt) per vial. This corresponds to 10.8% of the maximum recommended daily dietary sodium intake for adults.
This should be taken into account for patients on a controlled sodium diet.

3. How to use Piperacillin + Tazobactam Accord

This medicine will be administered by a doctor or other healthcare professional as an intravenous infusion (lasting 30 minutes) into one of the patient's veins.
Dosage
The dose of medicine given to the patient depends on the disease being treated, the patient's age, and any kidney problems the patient may have.
Adults and adolescents over 12 years of age
The usual dose is 4 g piperacillin and 0.5 g tazobactam, administered into one of the patient's veins (directly into the bloodstream) every 6 to 8 hours.
Children aged 2 to 12 years
For children with abdominal infections, the recommended dose is 100 mg piperacillin and 12.5 mg tazobactam per kg of body weight, administered into one of the patient's veins (directly into the bloodstream) every 8 hours. The usual dose for children with low white blood cell counts is 80 mg piperacillin and 10 mg tazobactam per kg of body weight, administered into one of the patient's veins (directly into the bloodstream) every 6 hours.
The doctor will calculate the dose 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 symptoms of infection 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. The doctor may perform blood tests to ensure the correct dose is being given, especially if the patient is receiving the medicine for a prolonged period.
Accidental overdose of Piperacillin + Tazobactam Accord
Piperacillin + Tazobactam Accord will be administered by a doctor or other healthcare professional, so the likelihood of receiving an incorrect dose is low. However, if the patient experiences adverse effects such as seizures or suspects having received too high a dose, this should be reported to the doctor immediately.
Missed dose of Piperacillin + Tazobactam Accord
If the patient suspects that a dose of Piperacillin + Tazobactam Accord has been missed, this should be reported immediately to the doctor or other healthcare professional.
If there are any further doubts regarding the use of this medicine, consult the doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If any of the potentially serious side effects of Piperacillin + Tazobactam Accord occur, you must immediately consult a doctor.
Serious side effects (with frequency stated in parentheses) of Piperacillin + Tazobactam Accord include:

• severe skin reactions [Stevens-Johnson syndrome, bullous dermatitis (frequency not known), exfoliative dermatitis (frequency not known), toxic epidermal necrolysis (rare)], initially appearing as red spots resembling targets or circular lesions occurring on the trunk. Additionally, ulceration of the mouth, throat, nose, limbs, genital organs, and conjunctivitis (redness and swelling of the eyes) may occur. The rash may progress to extensive blisters or skin peeling and may be life-threatening.
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms), which may involve the skin and, more importantly, other organs beneath the skin, such as the kidneys and liver.
• skin disease (acute generalized exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled blisters located on a swollen and red large skin surface.
• 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 (not very common), itching or rash on the skin (common).
• yellowing of the skin or whites of the eyes (frequency not known).
• damage to blood cells [symptoms include: unexpected shortness of breath, red or brown discoloration of urine (frequency not known), nosebleeds (rare), and small bruises (frequency not known)], significant decrease in white blood cells (rare).
• severe or persistent diarrhoea with fever or weakness (rare).

If any of these side effects worsens or if any side effects not listed in this leaflet occur, inform your doctor or other healthcare professional immediately.
Very common side effects (may occur in more than 1 in 10 people):

• diarrhoea

Common side effects (may occur in less than 1 in 10 people):

• fungal infections (e.g. candidiasis)
• reduced platelet count, reduced red blood cell count or haemoglobin, abnormal laboratory test results (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, gastrointestinal discomfort
• increased liver enzyme activity in blood
• skin rash, itching
• abnormal blood test results indicating kidney function
• fever, injection site reaction

Uncommon side effects (may occur in less than 1 in 100 people):

• reduced white blood cell count (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
• decreased potassium levels in blood, decreased blood glucose levels
• seizures observed in patients receiving high doses of the medicine or in those with kidney problems
• low blood pressure, phlebitis (feeling of excessive sensitivity to touch or redness of the inflamed area), skin redness
• increased levels of breakdown product of blood pigment (bilirubin)
• skin reactions including redness, skin lesions, urticaria
• joint and muscle pain
• chills

Rare side effects (may occur in less than 1 in 1000 people):

• significant reduction in white blood cell count (agranulocytosis), nosebleeds
• severe infection of the large intestine, inflammation of the mucous membrane of the mouth
• detachment of the outer layer of skin over the entire body (toxic epidermal necrolysis)

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

• significant reduction in red blood cells, white blood cells, and platelets (pancytopenia), reduced white blood cell count (neutropenia), reduced red blood cell count due to premature destruction or degradation, small bruises, prolonged bleeding time, increased platelet count, increased number of a specific type of white blood cells (eosinophilia)
• allergic reaction and severe allergic reaction
• hepatitis, yellowing of the skin or whites of the eyes
• severe systemic allergic reaction with skin rash and mucous membrane lesions, blisters, and other skin eruptions (Stevens-Johnson syndrome), severe allergic reaction affecting the skin and other organs such as kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters on swollen and red large skin areas with fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
• impaired kidney function and kidney diseases
• lung disease characterized by increasing numbers of eosinophils (a type of white blood cell) in the lungs
• acute disorientation and confusion (delirium)

Piperacillin administration has been associated with a higher incidence of fever and rash in patients with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin with tazobactam, may lead to symptoms of brain dysfunction (encephalopathy) and seizures.
Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps provide 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 stated month.
No special storage conditions are required for this medicine.
Reconstituted and/or diluted solutions should be used immediately.
From a microbiological point of view, the product should be used immediately. If not used
immediately, the responsibility for storage duration and conditions prior to use lies with the user.
For single use only. Any unused solution should be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack 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 sodium piperacillin) and 0.25 g of tazobactam (as sodium tazobactam).
Piperacillin + Tazobactam Accord 4 g + 0.5 g
Each vial contains 4 g of piperacillin (as sodium piperacillin) and 0.5 g of tazobactam (as sodium tazobactam).
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 cardboard box.
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 cardboard box.
Not all pack sizes may be marketed.

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

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

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

Information intended exclusively for healthcare professionals:

Warning: Use is not recommended in adult patients for the treatment of bacteraemia caused by
E. coli and K. pneumoniae strains (ceftriaxone-resistant) producing extended-spectrum beta-lactamases (ESBL).
Instructions for use
Piperacillin + Tazobactam Accord should be administered by intravenous infusion (lasting 30 minutes).
Intravenous administration
Reconstitute the vial by adding the appropriate volume of one of the compatible reconstitution solvents listed below. Shake the vial until the powder is completely dissolved. The powder dissolves within 5 to 10 minutes of continuous shaking (detailed instructions for handling the medicinal product are provided below).

* Compatible solvents used for dissolution:

• 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 prepared solution should be withdrawn from the vial using a syringe. After dissolving the powder
as recommended, the content of the vial withdrawn with a syringe will contain the amount of piperacillin and tazobactam stated on the label.
The solution thus prepared may be further diluted to the required volume (e.g., 50 mL to 150 mL) using one of the following diluents:

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

Pharmaceutical incompatibilities
If Piperacillin + Tazobactam Accord is administered simultaneously with other antibiotics (e.g.,
aminoglycosides), these drugs should be given separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.
Piperacillin + Tazobactam Accord must not be mixed with other medicinal products in the same syringe or infusion bottle, as compatibility has not been established.
Due to chemical instability, Piperacillin + Tazobactam Accord must not be used with solutions containing sodium bicarbonate.
Ringer's lactate solution (Hartmann's solution) is pharmaceutically incompatible with Piperacillin + Tazobactam Accord.
Piperacillin + Tazobactam Accord must not be added to blood products or albumin hydrolysates.