PIPERACILLIN/TAZOBACTAM ACCORDPHARMA 4/0.5 g POWDER FOR INJECTION SOLUTION

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

Do not use Piperacillin/Tazobactam Accordpharma

• if you are allergic to piperacillin or tazobactam 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 Accordpharma.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Piperacillin/Tazobactam Accordpharma if:

• You have allergies. If you have multiple allergies, make sure to tell your doctor or other healthcare professional before receiving this product.
• You had 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.
• 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.
• 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.
• You are using certain medicines (called anticoagulants) to prevent excessive blood clotting (see also Other medicines and Piperacillin/Tazobactam Accordpharmain this leaflet) or if you experience unexpected bleeding during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• You experience seizures during treatment. In this case, you must inform your doctor or other healthcare professional immediately.
• You think you have developed a new infection or your infection has worsened. In this case, you must inform your doctor or other healthcare professional immediately.
• 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 Accordpharma and seek medical attention immediately if you notice any of the symptoms described in section 4.
• Hemophagocytic lymphohistiocytosis

There have been reports of a disease in which the immune system produces too many white blood cells, otherwise normal, 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 under 2 yearsPiperacillin/Tazobactam Accordpharma is not recommended for use in children under 2 years of age due to the lack of safety and efficacy data.

Other medicines and Piperacillin/Tazobactam Accordpharma

Tell your doctor or nurse that 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 containing other antibiotics such as tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Using 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 receiving 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 Accordpharma is suitable for you.

Driving and using machines

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

Piperacillin/Tazobactam Accordpharma 4g/0.5g contains sodium.

This medicine contains 216 mg of sodium (the main component of cooking/table salt). This is equivalent to 10.8% of the maximum recommended daily intake of sodium for an adult.

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3. How to use Piperacillin/Tazobactam Accordpharma

Your doctor or other healthcare professional will administer this medicine to you through intravenous infusion (in a vein with a drip for 30 minutes). The dose of medicine that you will receive depends on the disease being treated, 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 dose will not exceed 4 g/0.5 g of Piperacillin/Tazobactam Accordpharma.

You will receive Piperacillin/Tazobactam Accordpharma until the signs of infection have completely disappeared (5 to 14 days).

Patients with kidney problems

Your doctor may need to reduce the dose of Piperacillin/Tazobactam Accordpharma 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 Accordpharma than you should:

Since a doctor or other healthcare professional will administer Piperacillin/Tazobactam Accordpharma 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 Accordpharma

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

If you have any further questions on the use of this product, ask your doctor or pharmacist.

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 Accordpharma are:

• Severe skin reactions [Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] that initially appear 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 can potentially be fatal.
• Potentially life-threatening allergic reaction (drug reaction with eosinophilia and systemic symptoms) that can affect the skin and other vital organs such as the kidneys and liver (not known).
• A skin disease (acute generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small fluid-filled blisters that appear on large areas of swollen and reddened skin (not known).
• 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, urticaria (uncommon), itching, or skin 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)].
• Persistent or severe diarrhea accompanied by fever or weakness (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):

• Fungal infection.
• Decrease in platelets, decrease in red blood cells or hemoglobin (blood pigment), abnormal laboratory tests (positive direct Coombs test), prolonged blood clotting time (prolonged activated partial thromboplastin time).
• Decrease in blood proteins.
• Headache, insomnia.
• Abdominal pain, vomiting, nausea, constipation, stomach upset.
• Increased 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 (leukopenia), prolonged blood clotting time (prolonged prothrombin time).
• Seizures (convulsions), observed in patients receiving high doses or with kidney problems.
• Decrease in potassium levels in the blood, decrease in blood sugar levels.
• Low blood pressure, inflammation of the veins (pain when touched or redness of the affected area), skin redness.
• Increased levels of a breakdown product of the blood pigment (bilirubin).

• Skin reactions with redness, formation of skin lesions, and urticaria.
• 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 hematoma, prolonged bleeding time, increased platelets, increased levels of a specific type of white blood cells (eosinophilia).
• Allergic reaction and severe allergic reaction.
• Liver inflammation, yellowing of the skin or the whites of the eyes.
• Severe allergic reaction affecting the whole body with skin and mucous membrane rashes, blisters, and various skin rashes (Stevens-Johnson syndrome), severe allergic reactions affecting the skin and other organs such as the kidneys and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters 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 confusion and disorientation (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 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 that they are 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 Accordpharma

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 and vial after “EXP”. The expiry date refers to the last day of the month shown.

Unopened vials: No special storage conditions are required.

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. Contents of the pack and other information

Composition of Piperacilina/Tazobactam Accordpharma

• The active ingredients are piperacillin and tazobactam.

Each vial contains 4 g of piperacillin (as sodium salt) and 0.5 g of tazobactam (as sodium salt).

Appearance of the product and packaging content

Piperacilina/Tazobactam Accordpharma 4 g/0.5 g is a white or off-white powder supplied in a vial.

The packages contain 1 vial and 1 sterile fluid transfer set.

The clinical packages contain 50 vials and 50 sterile fluid transfer sets.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Accord Healthcare S.L.U.

World Trade Center. Moll de Barcelona, s/n, Edifici Est, 6ª planta.

08039, Barcelona (Spain)

Manufacturer:

LABORATORIO REIG JOFRÉ, S.A.

C/ Jarama s/n Pol. Ind.

45007 – Toledo

Spain

o

MITIM, S.R.L.

Via Cacciamali, 34-38

Brescia

25125 – Italy

o

ACCORD HEALTHCARE POLSKA SP. Z O.O.

Magazyn Importera, ul.

Lutomierska, 50,

Pabianice, 95-200

Poland

Date of revision of this prospectus:December 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 solely for doctors or healthcare professionals:

Instructions for use

Piperacilina/Tazobactam Accordpharma will be administered by intravenous infusion (drip for 30 minutes).

Intravenous route

To facilitate the reconstitution of the vial, invert it and shake it to loosen the powder adhering to the walls. Add the solvent and shake until completely dissolved.

Each vial should be reconstituted with the volume of solvent shown in the following table, using one of the compatible solvents for its 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:
  • Sterile water for injectable preparations 1).
  • Bacteriostatic water for injection.
  • Physiological serum (sodium chloride 0.9% in water).

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

The reconstituted solutions should be withdrawn from the vial with a syringe. After reconstitution as indicated, the vial content 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:

• Sterile water for injection.
• Physiological solution (sodium chloride 0.9% in water).
• Glucose solution (Dextrose 5% in water).
• Solution (Dextrose 5% and sodium chloride 0.9% in water).

Incompatibilities

Whenever Piperacilina/Tazobactam Accordpharma is used simultaneously with another antibiotic (e.g., aminoglycosides), these should be administered separately. The mixture of beta-lactam antibiotics with aminoglycosides in vitromay result in substantial inactivation of the aminoglycoside.

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

Due to chemical instability, Piperacilina/Tazobactam Accordpharma should not be used with solutions containing only sodium bicarbonate.

Piperacilina/Tazobactam Accordpharma is not compatible with Ringer's lactate solution.

Piperacilina/Tazobactam Accordpharma should not be added to hemoderivatives or albumin hydrolysates.