PIPERACILLIN/TAZOBACTAM KABI 2 g/0.25 g POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you use Piperacillin/Tazobactam Kabi

Do not use Piperacillin/Tazobactam Kabi

• 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 called penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may be allergic to Piperacillin/Tazobactam Kabi.

Warnings and precautions

Talk to your doctor or nurse before you start using Piperacillin/Tazobactam Kabi

• if you have allergies. If you have multiple allergies, make sure to tell your doctor or other healthcare professional before receiving this product.
• if you had diarrhea before treatment or if you start having it during or after treatment. In this case, make sure to tell your doctor or other healthcare professional immediately. Do not take any medicine for diarrhea without consulting your doctor first.
• if you have low potassium levels in your blood. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment.
• if you have kidney or liver problems, or if you are on hemodialysis. Your doctor may want to examine your kidneys before you receive this medicine and may perform periodic blood tests during treatment.
• if you are using certain medicines (called anticoagulants) to prevent excessive blood clotting (see also Using Piperacillin/Tazobactam Kabi with other medicinesin this leaflet) or if you experience unexpected bleeding during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• if you are taking another antibiotic called vancomycin at the same time as Piperacillin/Tazobactam, this may increase the risk of kidney damage (see also Using Piperacillin/Tazobactam Fresenius Kabi with other medicinesin this leaflet).
• if you experience seizures during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• if you think you have developed a new infection or if your infection has worsened. In this case, you must inform your doctor or other healthcare professional immediately.
• if you have severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP). Stop using Piperacillin/Tazobactam Fresenius Kabi and seek immediate medical attention if you notice any of the symptoms described in section 4.

Hemophagocytic lymphohistiocytosis

Cases of a disease in which the immune system produces too many white blood cells, namely histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis) have been reported. This disease can be potentially fatal if not diagnosed and treated early. If you experience multiple symptoms such as fever, swelling of the lymph nodes, feeling of weakness, feeling of dizziness, difficulty breathing, bruising, or skin rash, contact your doctor immediately.

Children under 2 years

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

Using Piperacillin/Tazobactam Kabi with other medicines

Tell your doctor or pharmacist that you are using, have recently used, or might use any other medicines. Some medicines may interact with piperacillin or tazobactam.

These include:

• a medicine for gout (probenecid). This product may increase the time it takes for piperacillin and tazobactam to be eliminated from the body
• medicines used to thin the blood or to treat blood clots (e.g., heparin, warfarin, or acetylsalicylic acid).
• medicines used to relax muscles during surgery. Inform your doctor if you are going to undergo general anesthesia.
• 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 decrease potassium levels in the blood (e.g., diuretic pills or some cancer medicines).
• medicines that contain other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking Piperacillin/Tazobactam and vancomycin at the same time may increase the risk of kidney damage even if you do not have kidney problems.

Effects on laboratory tests

If you need to provide a blood or urine sample, tell your doctor or laboratory staff that you are using Piperacillin/tazobactam.

Pregnancy and breastfeeding

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 if Piperacillin/Tazobactam Kabi is suitable for you.

Piperacillin and tazobactam may pass to the baby in the womb or through breast milk. If you are breastfeeding a child, your doctor will decide if Piperacillin/Tazobactam Kabi is suitable for you.

Driving and using machines

It is not expected that the use of Piperacillin/Tazobactam Kabi will affect your ability to drive or use machines.

Piperacillin/Tazobactam Kabi 2 g/0.25 g contains112 mg of sodium (main component of table salt/cooking salt) in each vial. This is equivalent to 5.6% of the maximum recommended daily intake of sodium for an adult.

3. How to use Piperacillin/Tazobactam Kabi

Your doctor or other healthcare professional will administer this medicine to you by intravenous infusion (into a vein with a drip over 30 minutes). The dose of medicine that you will be given depends on the disease you are being treated for, your age, and whether or not you have kidney problems.

Adults and adolescents 12 years and older

The recommended dose is 4 g/0.5 g of piperacillin/tazobactam administered every 6-8 hours through a vein (directly into the bloodstream).

Children 2 to 12 years of age

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

Your doctor will calculate the dose based on the child's weight, but each individual dosewill not exceed 4 g/0.5 g of Piperacillin/Tazobactam Kabi.

You will be given Piperacillin/Tazobactam Kabi until the signs of infection have completely disappeared (from 5 to 14 days).

Patients with kidney problems

It may be necessary for your doctor to reduce the dose of Piperacillin/Tazobactam Kabi or the frequency of administration. Your doctor may also want to perform blood tests to ensure that you are receiving the correct dose of treatment, especially if you need to use this medicine for a long time.

If you use more Piperacillin/Tazobactam Kabi than you should

Since a doctor or other healthcare professional will be administering Piperacillin/Tazobactam Kabi to you, it is unlikely that you will receive an incorrect dose. However, if you experience side effects, such as seizures, or think you have been given too much medicine, tell your doctor immediately.

If you miss a dose of Piperacillin/Tazobactam Kabi

If you think you have missed a dose of Piperacillin/Tazobactam Kabi, tell your doctor or other healthcare professional immediately.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you experience any of these potentially serious side effects of Piperacillin/Tazobactam.

The serious side effects (with frequency in parentheses) of Piperacillin/Tazobactam Kabi are:

• severe skin rash [Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] that initially appears as reddish spots or circular patches with central blisters on the torso. Other signs include ulcers in the mouth, throat, nose, limbs, genitals, and conjunctivitis (red and swollen eyes). The rash can progress to blistering or peeling of the skin and can potentially be fatal
• potentially serious allergic reaction [drug reaction with eosinophilia and systemic symptoms (DRESS)] that can affect the skin and other major organs of the body such as the kidneys and liver
• a skin disease [acute generalized exanthematous pustulosis (AGEP)] accompanied by fever, consisting of numerous small pus-filled bumps that appear on large areas of swollen and reddened skin

• 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 (common)
• yellowing of the eyes and skin (not known)
• damage to blood cells [symptoms include: shortness of breath when not expected, urine of red or brown color (not known), nosebleeds (rare), and small bruises (not known), severe decrease in white blood cells in the blood (rare)]

If any of the following side effects are severe or if you experience any side effect not mentioned in this leaflet, tell your doctor or other 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):

• yeast infection
• decrease in platelets, decrease in red blood cells or hemoglobin (blood pigment), abnormal laboratory tests (direct Coombs test positive), prolonged blood clotting time (prolonged activated partial thromboplastin time)
• decrease in blood proteins
• headache, insomnia
• abdominal pain, vomiting, nausea, constipation, stomach upset
• increase in liver enzymes in the blood
• skin rash, itching
• abnormal kidney blood tests
• fever, reaction at the injection site

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

• decrease in white blood cells in the blood (leucopenia), prolonged blood clotting time (prolonged prothrombin time)
• decrease in potassium levels in the blood, decrease in blood sugar levels
• seizures (convulsions), observed in patients receiving high doses or with kidney problems
• low blood pressure, inflammation of the veins (pain when touching or redness of the affected area), reddening of the skin
• increase in a breakdown product of the blood pigment (bilirubin)
• skin reactions with reddening, formation of skin lesions, hives
• muscle and joint pain
• chills

Rare side 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
• shedding of the top layer of the skin all over the body (toxic epidermal necrolysis)

Side effects with unknown frequency (cannot be estimated from the 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 bruise, prolonged bleeding time, increase in 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 the whites of the eyes
• severe allergic reaction all over the body with skin and mucous membrane rashes, blisters, and various skin rashes (Stevens-Johnson syndrome), severe allergic reactions that affect the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small pus-filled bumps that appear on large areas of swollen and reddened skin accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
• kidney function impairment and kidney problems
• a type of lung disease where eosinophils (a type of white blood cell) appear in the lungs in greater numbers
• acute disorientation and confusion (delirium).

In patients with cystic fibrosis, treatment with piperacillin has been associated with an increased incidence of fever and skin rash.

Beta-lactam antibiotics, including piperacillin/tazobactam, may cause manifestations of encephalopathy and seizures.

Reporting of side effects

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

5. Storage of Piperacillin/Tazobactam Kabi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month shown.

Unopened vials: Do not store above 25°C.

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 no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Piperacillin/Tazobactam Kabi

The active ingredients are piperacillin and tazobactam

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

There are no other components.

Appearance of the Product and Container Contents

Piperacillin/Tazobactam Kabi 2 g/0.25 g is a sterile lyophilized white or off-white powder for solution for infusion.

Piperacillin/Tazobactam Kabi 2 g/0.25 g is available in 10 ml and 50 ml colorless glass vials (type II) closed with a halobutyl rubber stopper.

Formats: 1, 5, and 10 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Fresenius Kabi España S.A.U

C/ Marina 16-18,

08005 - Barcelona

Spain

Manufacturer:

LABESFAL - Laboratórios Almiro S.A.

FRESENIUS KABI GROUP

3465-157 Santiago de Besteiros

PORTUGAL

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

Date of the last revision of this leaflet: November 2021

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

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This information is intended only for healthcare professionals:

The following text is an excerpt from the Summary of Product Characteristics that serves as a guide in the administration of Piperacillin/Tazobactam Kabi. When determining the suitability of use in a particular patient, the prescribing physician must be familiar with the Summary of Product Characteristics.

Incompatibilities with solvents and other medicinal products

RINGER LACTATE solution is NOT compatible with Piperacillin/Tazobactam Kabi.

When using piperacillin/tazobactam in combination with another antibiotic (e.g., AMINOGLYCOSIDE), the medicinal products must be administered SEPARATELY. The mixture of Piperacillin/Tazobactam Kabi with an aminoglycoside in vitro may cause substantial inactivation of the aminoglycoside.

Piperacillin/Tazobactam Kabi must be ADMINISTERED through an infusion set SEPARATELY from any other medicinal product unless its compatibility has been demonstrated.

Due to chemical instability, Piperacillin/Tazobactam Kabi MUST NOT be used with solutions containing SODIUM BICARBONATE.

Piperacillin/Tazobactam Kabi MUST NOT be added to BLOOD PRODUCTS or HYDROLIZED ALBUMIN.

Instructions for use

Piperacillin/tazobactam will be administered by intravenous infusion (drip over 30 minutes).

Intravenous route

Each vial must be reconstituted with the volume of solvent shown in the following table, using one of the compatible solvents for reconstitution. Shake with rotary movements until dissolved. If shaken constantly, it is usually reconstituted within 5 to 10 minutes (see handling details below).

• Compatible solvents for reconstitution:
  • Sodium chloride 0.9% injectable solution (9 mg/ml)
  • Sterile water for injectable preparations(1)

(1) The maximum recommended volume of sterile water for injectable preparations per dose is 50 ml.

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

The reconstituted solutions may be further diluted to the desired volume (e.g., from 50 ml to 150 ml) with one of the following compatible solvents:

• Sodium chloride 0.9% injectable solution (9 mg/ml)
• Glucose 5%
• Dextran 6% in sodium chloride 0.9%