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

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

Do not use Piperacillin/Tazobactam Tillomed

• if you are allergic to piperacillin sodium, tazobactam sodium, or 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.

Warnings and precautions

Consult your doctor or pharmacist or nurse before starting to use piperacillin/tazobactam:

• 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 have diarrhea before treatment or if you start to have 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 are taking another antibiotic called vancomycin at the same time as piperacillin/tazobactam, this may increase the risk of kidney damage (see also “Other medicines and Piperacillin/Tazobactam Tillomed” below)
• 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 undergoing 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 “Other medicines and Piperacillin/Tazobactam Tillomed” in 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 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

Hemophagocytic lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many white blood cells, called histiocytes and lymphocytes, causing inflammation (hemophagocytic lymphohistiocytosis). 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

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

Other medicines and Piperacillin/Tazobactam Tillomed

Tell your doctor, pharmacist, or other healthcare professional if you are using, have recently used, or might use 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 product 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 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 certain cancer medicines)
• medicines that contain other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. The use of 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 other healthcare professional before using this medicine. Your doctor will decide if piperacillin/tazobactam 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 is suitable for you.

Driving and using machines

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

Piperacillin/Tazobactam Tillomed 2g/0.25g contains sodium (as part of the active ingredient)

This medicine contains 108.05 mg of sodium (a major component of table salt/cooking salt) in each vial. This is equivalent to 5.4% of the maximum recommended daily intake of sodium for an adult.

3. How to use Piperacillin/Tazobactam Tillomed

Your doctor or other healthcare professional will administer this medicine to you by intravenous infusion (into a vein with a drip over 30 minutes).

Dose

The dose of medicine that you will be given depends on the disease being treated, your age, and whether you have kidney problems.

Adults and adolescents over 12 years of age

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

Children from 2 to 12 years of age

The usual 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 dose will not exceed 4 g/0.5 g of piperacillin/tazobactam.

You will be given piperacillin/tazobactam 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 or the frequency of administration. Your doctor may also want to perform blood tests to ensure 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 Tillomed than you should

Since a doctor or other healthcare professional will be administering piperacillin/tazobactam 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.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you miss a dose of Piperacillin/Tazobactam Tillomed

If you think you have missed a dose of piperacillin/tazobactam, tell your doctor or other healthcare professional immediately.

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

4. Possible side effects

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

Consult a 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 are:

• severe skin rashes [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 trunk. 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 potentially be fatal
• severe allergic reaction that can affect the skin and other organs such as the kidneys or liver (drug reaction with eosinophilia and systemic symptoms) (frequency not known)
• a skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small pus-filled blisters that appear in 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 or widespread rash (uncommon), itching or rash (common)
• yellowing of the eyes and skin (not known)
• blood cell damage (symptoms include: shortness of breath when not expected, urine that is red or brown in color (not known), nosebleeds (rare), bruising (not known), severe decrease in white blood cells in the blood (rare))
• severe or persistent diarrhea accompanied by fever or weakness (rare)

If any of the followingside effects become serious or if you notice any side effects 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 or 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 function 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 (leukopenia), prolonged blood clotting time (prolonged prothrombin time)
• decrease in potassium levels in the blood, decrease in blood sugar levels
• seizures (convulsions), observed in patients with high doses or kidney problems
• low blood pressure, inflammation of the veins (sensitivity or redness of the affected area), redness of the skin
• increase in a breakdown product of blood pigment (bilirubin)
• skin reactions with redness, 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 frequency not known (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 destruction, small bruises, 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 affecting the skin and other organs such as the kidneys and liver (Stevens-Johnson syndrome), severe allergic disorder 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 contained within large areas of swollen and reddened skin accompanied by fever (acute generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis)
• kidney problems and kidney failure
• 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 rashes.

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

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any 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 Tillomed

Keep out of sight and reach of children.

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

No special storage conditions are required.

Reconstituted/diluted solution for infusion

Chemical and physical stability has been demonstrated for 12 hours at 25°C and for 48 hours at 2-8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

The vials should not be frozen after reconstitution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and further information

Composition of Piperacillin/Tazobactam Tillomed

Piperacillin/Tazobactam Tillomed 2 g/0.25 g

• The active substances are piperacillin and tazobactam.
• Each vial contains 2 g of piperacillin (as piperacillin sodium) and 0.25 g of tazobactam (as tazobactam sodium).
• This medicinal product does not contain any other ingredients besides the active substances.

Appearance and packaging of the product

The medicinal product is a white to off-white powder or agglomerate for solution for infusion.

The medicinal product is available in 30 ml Type I glass vials with bromobutyl rubber stoppers and a combined plastic and aluminum gray cap.

Package sizes: 1 or 10 vials.

Not all package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Laboratorios Tillomed Spain, S.L.U.

c/ Cardenal Marcelo Spínola 8

28016 Madrid

Spain

Manufacturer: (1)

MIAS Pharma Limited

Suite 2

Stafford House, Strand Road

Portmarnock

D13 H525

Ireland

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola PLA 3000, Malta

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000,

Malta

(1) Only the actual manufacturer will be indicated on the label.

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

Germany: Piperacillin/Tazobactam Tillomed 2 g/0.25 g Powder for solution for infusion

France: Piperacilline/Tazobactam Tillomed 2 g/0.25 g Powder for solution for infusion

Italy: Piperacillin/Tazobactam Tillomed

Netherlands: Piperacilline/Tazobactam Tillomed 2 g/0.25 g Powder for solution for infusion

Spain: Piperacilina/Tazobactam Tillomed 2 g/0.25 g Powder for solution for infusion EFG

Date of the last revision of this leaflet: November 2022

Detailed 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.

This information is intended only for healthcare professionals:

Instructions for use

Piperacillin/Tazobactam should be administered by intravenous infusion (drip over 30 minutes).

Instructions for reconstitution and dilution

Reconstitute each vial with the volume of solvent shown in the following table, using one of the compatible solvents for reconstitution. Shake until dissolved. When constantly shaken, reconstitution generally occurs within 5 to 10 minutes (see handling details below).

• Compatible solvents for reconstitution:
  • Sodium chloride 9 mg/ml (0.9%) injection solution
  • Sterile water for injection (1)
  • Glucose 50 mg/ml (5%) injection solution

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

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

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

• Sodium chloride 9 mg/ml (0.9%) injection solution
• Glucose 50 mg/ml (5%)
• Dextran 60 mg/ml (6%) in sodium chloride 9 mg/ml (0.9%).

Incompatibilities

Whenever this product is used simultaneously with another antibiotic (e.g., aminoglycosides), the substances should be administered separately. The mixture of beta-lactam antibiotics with aminoglycosides in vitro may result in substantial inactivation of the aminoglycoside.

Piperacillin/Tazobactam Tillomed should not be mixed with other substances in a syringe or infusion bottle, as its compatibility has not been established.

Due to chemical instability, Piperacillin/Tazobactam should not be used with solutions that only contain sodium bicarbonate.

Piperacillin/Tazobactam Tillomed should not be added to hemoderivatives or albumin hydrolysates.

Piperacillin/Tazobactam Tillomed should not be used with Ringer's Lactate solution, Ringer's Acetate solution, Ringer's Acetate/Malate solution, or Hartmann's solution.