Piperacillin + tazobactam aptapharma

Package leaflet: Information for the user

Piperacillin + Tazobactam AptaPharma, 2 g + 0.25 g, powder for solution for infusion
Piperacillin + Tazobactam AptaPharma, 4 g + 0.5 g, powder for solution for infusion
Piperacillinum + Tazobactamum
Please read all of this leaflet carefully before this medicine is administered 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.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

1. What Piperacillin + Tazobactam AptaPharma 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 more strains of bacteria are killed when piperacillin and tazobactam are used together.
Piperacillin + Tazobactam AptaPharma 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. This medicine may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin + Tazobactam AptaPharma is used in children aged 2 to 12 years to treat infections of the abdominal cavity, including appendicitis, peritonitis (infection of fluid and membrane inside abdominal organs), and cholecystitis (gallbladder or bile duct infection). This medicine 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 AptaPharma together with other antibiotics.

2. Important information before receiving Piperacillin + Tazobactam AptaPharma

When not to use Piperacillin + Tazobactam AptaPharma

• If you are allergic to piperacillin or tazobactam.
• If you are allergic to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to Piperacillin + Tazobactam AptaPharma.

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

• If you have allergies. If you have multiple allergies, ensure you have informed your doctor or healthcare professional before taking this medicine.
• If you have diarrhoea before treatment, or if it develops during or after treatment. Inform your doctor or healthcare professional immediately. Do not take any anti-diarrhoeal medicines without consulting your doctor.
• If you have low potassium levels in your blood. Your doctor may check your kidney function before treatment and perform regular blood tests during treatment.
• If you have kidney or liver problems, or are undergoing haemodialysis. Your doctor may check your kidney function before treatment and perform regular blood tests during treatment.
• If you are taking another antibiotic called vancomycin at the same time as Piperacillin + Tazobactam AptaPharma, as the risk of kidney damage may be increased (see also Piperacillin + Tazobactam AptaPharma and other medicines in this leaflet).
• If you are taking certain medicines (called anticoagulants) that prevent excessive blood clotting (see also Piperacillin + Tazobactam AptaPharma and other medicines in this leaflet) or if unexpected bleeding occurs during treatment. Inform your doctor or healthcare professional immediately.
• If you experience seizures during treatment. Inform your doctor or healthcare professional immediately.
• If you suspect you have developed a new infection or an existing infection has worsened. Inform your 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 early and treated. If you experience multiple symptoms such as fever, swollen lymph nodes, feeling weak, dizziness, shortness of breath, cyanosis or skin rash, contact your 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 AptaPharma and other medicines
Tell your doctor or healthcare professional about all medicines you are currently taking, have recently taken, or plan to take, including those obtained without a prescription. Some medicines may interact with piperacillin and tazobactam.
These include:

• 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, acetylsalicylic acid).
• Medicines used to relax muscles during surgery. If you are to undergo general anaesthesia, inform your doctor that you are receiving 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. Inform your doctor if you have kidney problems. Concurrent use of Piperacillin + Tazobactam AptaPharma and vancomycin may increase the risk of kidney damage, even if you do not have kidney disease.

Effect on laboratory test results
If you are to provide a blood or urine sample, inform your doctor or laboratory staff that you are receiving Piperacillin + Tazobactam AptaPharma.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or healthcare professional before receiving this medicine.
Your doctor will decide whether Piperacillin + Tazobactam AptaPharma is appropriate for you. Piperacillin and tazobactam may pass to the unborn child or through breast milk. If you are breastfeeding, your doctor will decide whether Piperacillin + Tazobactam AptaPharma is appropriate for you.
Driving and using machines
Piperacillin + Tazobactam AptaPharma is not expected to affect the ability to drive or use machines.
Piperacillin + Tazobactam AptaPharma contains sodium
Piperacillin + Tazobactam AptaPharma 2 g + 0.25 g
This medicine contains 108 mg of sodium (the main component of table salt) in each vial. This corresponds to 5.4% of the maximum recommended daily dietary sodium intake for adults.
Piperacillin + Tazobactam AptaPharma 4 g + 0.5 g
This medicine contains 216 mg of sodium (the main component of table salt) in each vial. This corresponds to 10.8% of the maximum recommended daily dietary sodium intake for adults.
This should be taken into account in patients who are controlling their dietary sodium intake.

3. How to use Piperacillin + Tazobactam AptaPharma

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 the 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 + 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
In children with abdominal infections, the recommended dose is 100 mg piperacillin + 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 in children with low white blood cell counts is 80 mg piperacillin + 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 AptaPharma will not exceed 4 g + 0.5 g.
The patient will receive Piperacillin + Tazobactam AptaPharma until the signs of infection have completely resolved (for 5 to 14 days).
Patients with kidney disease
The doctor may recommend reducing the dose of Piperacillin + Tazobactam AptaPharma 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.
Overdose of Piperacillin + Tazobactam AptaPharma
Piperacillin + Tazobactam AptaPharma will be administered to the patient by a doctor or other healthcare professional, so incorrect dosing is unlikely.
However, if the patient experiences adverse effects such as seizures, or if the patient suspects they have received too high a dose, this should be reported to the doctor immediately.
Missed dose of Piperacillin + Tazobactam AptaPharma
If the patient suspects that a dose of Piperacillin + Tazobactam AptaPharma has been missed, this should be reported immediately to the doctor or other healthcare professional.
If there are any further doubts concerning the use of this medicine, consult the doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If any of the potentially serious adverse effects of Piperacillin + Tazobactam AptaPharma occur, you should immediately consult a doctor (frequency is given in brackets):

• severe skin rash [Stevens-Johnson syndrome, bullous dermatitis (frequency unknown), exfoliative dermatitis (frequency unknown), toxic epidermal necrolysis (rare)], initially appearing as red, target-shaped or circular spots occurring on the trunk. Additionally, ulceration of the mouth, throat, nose, limbs, genital organs and inflammation of the conjunctiva (redness and swelling of the eyes) may occur. The rash may progress to extensive blistering or skin peeling and may be life-threatening.
• severe, potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms), which may affect the skin and, more importantly, internal organs such as the kidneys and liver (frequency unknown).
• skin disease (acute generalized exanthematous pustulosis) accompanied by fever, manifesting as numerous small fluid-filled blisters located on a swollen and reddened large area of skin (frequency unknown).
• swelling of the face, lips, tongue or other parts of the body (frequency unknown).
• shortness of breath, wheezing or difficulty breathing (frequency unknown).
• severe rash or urticaria (not very common), itching or skin rash (common).
• yellowing of the skin or whites of the eyes (frequency unknown).
• blood cell damage [symptoms include: unexpected shortness of breath, red or brown discoloration of urine (frequency unknown), nosebleeds (rare), and small bruises (frequency unknown)], significant decrease in white blood cell count (rare).
• severe or persistent diarrhoea with fever or weakness (rare). If any of these adverse effects worsen or if any adverse effects not listed in this leaflet occur, you should inform your doctor or other healthcare professional.

Very common adverse effects (may occur in more than 1 in 10 people):

• diarrhoea

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

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

Not very common adverse effects (may occur in less than 1 in 100 people):

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

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

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

Frequency unknown (frequency cannot be determined from available data):

• significant decrease in red blood cells, white blood cells and platelets (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 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 the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters located on a swollen and reddened large area of skin accompanied by fever (acute generalized exanthematous pustulosis), blistering skin reactions (bullous dermatitis)
• impaired kidney function and kidney diseases
• lung disease characterized by increasing accumulation 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 cause symptoms of brain dysfunction (encephalopathy) and seizures.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, you should inform your doctor or nurse. Adverse 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Piperacillin + Tazobactam AptaPharma

Keep the 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.
Unopened vial: Store below 25°C.
After reconstitution / dilution
Chemical and physical stability has been demonstrated for up to 24 hours after dissolution/dilution at controlled room temperature (25°C) and for up to 48 hours at 2–8°C. After dilution with Ringer's lactate solution or Hartmann's solution, the diluted solution should be used immediately after preparation.
From a microbiological point of view, the dissolved and diluted solutions should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 12 hours at 2–8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions. The storage conditions specified in the preceding paragraph should not be exceeded.
For single use only. Any unused solution should be discarded.
Medicines should not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Piperacillin + Tazobactam AptaPharma contains
The active substances in this medicinal product are piperacillin and tazobactam.
Piperacillin + Tazobactam AptaPharma 2 g + 0.25 g
Each vial contains sodium piperacillin (equivalent to 2 g of piperacillin) and sodium tazobactam
(equivalent to 0.25 g of tazobactam).
Piperacillin + Tazobactam AptaPharma 4 g + 0.5 g
Each vial contains sodium piperacillin (equivalent to 4 g of piperacillin) and sodium tazobactam
(equivalent to 0.5 g of tazobactam).

What Piperacillin + Tazobactam AptaPharma looks like and contents of the pack
Piperacillin + Tazobactam AptaPharma 2 g + 0.25 g
White or almost white powder in a 30 mL vial made of colourless glass (type I), with a bromobutyl rubber stopper and a violet flip-off aluminium-plastic seal, packed in a cardboard box.
Pack sizes: 1, 5 and 10 vials.

Piperacillin + Tazobactam AptaPharma 4 g + 0.5 g
White or almost white powder in a 48 mL vial made of colourless glass (type I), with a bromobutyl rubber stopper and a red flip-off aluminium-plastic seal, packed in a cardboard box.
Pack sizes: 1, 5 and 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Apta Medica Internacional d.o.o.
Likozarjeva ulica 6
1000 Ljubljana
Slovenia
Tel.: 00386 51 615 015
e-mail: [email protected]

Manufacturer/Importer
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Arrow Génériques
26 avenue Tony Garnier
Lyon, 69007
France

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

Information intended exclusively for medical professionals:

Warning: Use in adult patients is not recommended for the treatment of bacteremia caused by
E. coli and K. pneumoniae strains (resistant to ceftriaxone) producing extended-spectrum
beta-lactamases (ESBL).
How to store Piperacillin + Tazobactam AptaPharma
Unopened vial: Store below 25°C.
After reconstitution / dilution:
Chemical and physical stability has been demonstrated for up to 24 hours at controlled room temperature (25°C) and for up to 48 hours at 2–8°C. After dilution with Ringer's lactate solution or Hartmann's solution, the diluted solution must be used immediately after preparation.
From a microbiological standpoint, reconstituted and diluted solutions should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 12 hours at 2–8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions. The storage conditions specified above should not be exceeded.
Instructions for use
Piperacillin + Tazobactam AptaPharma should be administered as a 30-minute intravenous infusion.
The medicinal product, after reconstitution/dilution, is colorless to pale yellow.
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 administered if it is clear and free of visible particles.
Intravenous administration
Prepare the solution by adding the appropriate volume of one of the compatible diluents listed below to the vial. Shake the vial until the powder is completely dissolved. The powder dissolves within 5 to 10 minutes of continuous shaking (detailed handling instructions for the medicinal product are provided below).

* Compatible solvents used for reconstitution:

• Water for injections, sterile
• 0.9% (9 mg/mL) sodium chloride solution for injections
• 50 mg/mL (5%) glucose (dextrose) solution for injections
• 50 mg/mL (5%) glucose solution in 0.9% (9 mg/mL) sodium chloride solution for injections

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

• Water for injections, sterile (maximum recommended volume of sterile water for injections per dose is 50 mL)
• 0.9% (9 mg/mL) sodium chloride solution for injections
• 50 mg/mL (5%) glucose (dextrose) solution for injections
• 50 mg/mL (5%) glucose solution in 0.9% (9 mg/mL) sodium chloride solution for injections
• Ringer's solution with lactate
• Hartmann's solution
• Ringer's solution with acetate
• Ringer's solution with acetate and malate

Pharmaceutical incompatibilities
Piperacillin + Tazobactam AptaPharma must not be mixed with other medicinal products in the same syringe or infusion bottle, except as indicated above.
If Piperacillin + Tazobactam AptaPharma is administered concomitantly with other antibiotics (e.g., aminoglycosides), these should be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may lead to significant inactivation of the aminoglycoside. Piperacillin + Tazobactam AptaPharma 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 AptaPharma must not be used with solutions containing sodium bicarbonate. Piperacillin + Tazobactam AptaPharma must not be added to blood products or albumin hydrolysates.

Administration in combination with aminoglycosides
Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in inactivation of aminoglycosides. Therefore, it is recommended that Piperacillin + Tazobactam AptaPharma and aminoglycosides be administered separately. If simultaneous administration of an aminoglycoside and Piperacillin + Tazobactam AptaPharma is necessary, they should be reconstituted and diluted separately.
If simultaneous administration is indicated, Piperacillin + Tazobactam AptaPharma is compatible and may be administered simultaneously through a common infusion line (Y-site) exclusively with the following aminoglycosides and under the conditions described below:

* The dose of aminoglycoside should be adjusted according to the patient's body weight, severity of infection (severe or life-threatening), and renal function (creatinine clearance).
Compatibility of Piperacillin + Tazobactam AptaPharma with other aminoglycosides has not been established. Only the concentrations and solvents of amikacin and gentamicin mentioned above, together with the specified doses of Piperacillin + Tazobactam AptaPharma, have been determined as compatible for simultaneous administration via a common Y-site infusion line. Simultaneous administration via a common Y-site infusion line in any other manner than described above may result in inactivation of the aminoglycoside by Piperacillin + Tazobactam AptaPharma.
Any unused portions of the medicinal product or waste materials must be disposed of in accordance with local regulations.
For single use only. Any unused solution must be discarded.