Piperacillin and tazobactam Teva

Italy
Brand name Piperacillin and tazobactam Teva
Form solution for injection, powder and solvent
Active substance / Dosage
PIPERACILLIN SODIUM
SODIUM TAZOBACTAM
Prescription type Prescription only
ATC code
J01CR05
Registration number 037666
Manufacturer TEVA ITALIA S.R.L.
Piperacillin and tazobactam Teva solution for injection, powder and solvent

Table of Contents

Package leaflet: Information for the user

PIPERACILLIN AND TAZOBACTAM TEVA 2 g + 0.25 g/4 ml powder and solvent

for injectable solution for intramuscular use
PIPERACILLIN AND TAZOBACTAM TEVA 4 g + 0.5 g powder for solution for infusion
piperacillin/tazobactam
Generic medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
  • If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

  1. What Piperacillin and Tazobactam Teva is and what it is used for
  2. What you need to know before using Piperacillin and Tazobactam Teva
  3. How to use Piperacillin and Tazobactam Teva
  4. Possible side effects
  5. How to store Piperacillin and Tazobactam Teva
  6. Contents of the pack and other information

1. What Piperacillin and Tazobactam Teva is and what it is used for

Piperacillin belongs to a group of medicines known as "broad-spectrum penicillin antibiotics" and is capable of killing many types of bacteria. Tazobactam can prevent certain resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are administered together, they can kill a wider range of bacterial types.
Piperacillin and Tazobactam Teva is used in adults and adolescents for the treatment of bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin, or blood. Piperacillin and Tazobactam Teva may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
Piperacillin and Tazobactam Teva is used in children aged between 2 and 12 years for the treatment of abdominal infections, such as appendicitis, peritonitis (infection of the fluid and lining of abdominal organs), and gallbladder (biliary) infections. Piperacillin and Tazobactam Teva may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).
In certain severe infections, the doctor may consider using Piperacillin and Tazobactam Teva in combination with other antibiotics.

2. What you should know before using Piperacillin and Tazobactam Teva

Do not use Piperacillin and Tazobactam Teva

  • If you are allergic (hypersensitive) to piperacillin or tazobactam.
  • If you are allergic (hypersensitive) to antibiotics known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to Piperacillin and Tazobactam Teva.
  • If you are allergic (hypersensitive) to lidocaine (an excipient contained in the solvent for intramuscular use of Piperacillin and Tazobactam Teva 2 g + 0.25 g/4 ml powder and solvent for injectable solution for intramuscular use).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Piperacillin and Tazobactam Teva:

  • If you have allergies. If you have multiple allergies, inform your doctor or healthcare provider before receiving this medicine.
  • If you already have diarrhoea or if you develop diarrhoea during or after treatment. In this case, you must inform your doctor or healthcare provider immediately. Do not take medicines for diarrhoea without first consulting your doctor.
  • If you have low levels of potassium in the blood. Your doctor will need to check your kidney function before administering this medicine and may perform periodic blood tests during treatment.
  • If you are taking another antibiotic called vancomycin. Taking piperacillin and tazobactam together with vancomycin may increase the risk of kidney damage (see also section “Other medicines and Piperacillin and Tazobactam Teva” in this leaflet).
  • If you develop haemophagocytic lymphohistiocytosis. Cases of a disease in which the immune system produces higher than normal numbers of white blood cells called histiocytes and lymphocytes, leading to inflammation (haemophagocytic lymphohistiocytosis), have been reported. This condition can be life-threatening if not diagnosed and treated early. If you develop several symptoms such as fever, swollen lymph nodes, feeling weak, mental confusion, shortness of breath, bruising, or skin rash, contact your doctor immediately.
  • If you have kidney or liver problems or if you are undergoing haemodialysis. Your doctor will need to check your kidney function before administering this medicine and may perform periodic blood tests during treatment.
  • If you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also section “Other medicines and Piperacillin and Tazobactam Teva”), or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or healthcare provider immediately.
  • If you experience seizures during treatment. In this case, you must inform your doctor or healthcare provider immediately.
  • If you suspect you have developed a new infection or if your infection worsens. In this case, you must inform your doctor or healthcare provider immediately.

Children under 2 years of age
The use of piperacillin/tazobactam is not recommended in children under 2 years of age due to insufficient data on safety and efficacy.

Other medicines and Piperacillin and Tazobactam Teva
Inform your doctor or healthcare provider if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. Some medicines may interact with piperacillin and tazobactam.
These include:

  • Medicines for gout (probenecid). This may increase the time required for elimination of piperacillin and tazobactam from the body.
  • Medicines to thin the blood or treat blood clots (e.g. heparin, warfarin, or aspirin).
  • Medicines used to relax muscles during surgery. Inform your doctor if you are scheduled for general anaesthesia.
  • Methotrexate (a medicine used to treat cancer, arthritis, or psoriasis). Piperacillin and tazobactam may increase the time required for elimination of methotrexate from the body.
  • Medicines that may reduce potassium levels in the blood (e.g. diuretic tablets or certain cancer medicines).
  • Medicines containing the antibiotics 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.

Effect on laboratory tests
Inform your doctor or laboratory staff that you are taking Piperacillin and Tazobactam Teva if you are required to provide a blood or urine sample.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or healthcare provider before receiving this medicine.
Your doctor will decide whether Piperacillin and Tazobactam Teva is appropriate for you.
Piperacillin and tazobactam may pass to the baby in the womb or through breast milk. If you are breastfeeding, your doctor will decide whether Piperacillin and Tazobactam Teva is suitable for you.

Driving and using machines
Piperacillin and Tazobactam Teva is not expected to affect your ability to drive or use machinery.

Piperacillin and Tazobactam Teva contains sodium
Piperacillin and Tazobactam Teva 2 g + 0.25 g/4 ml contains 108 mg (4.69 mmol) of sodium per vial, while Piperacillin and Tazobactam Teva 4 g + 0.5 g contains 216 mg (9.38 mmol) of sodium per vial. This corresponds to 5.4% and 10.8%, respectively, of the maximum recommended daily dietary intake for an adult.

3. How to use Piperacillin and Tazobactam Teva

Piperacillin and Tazobactam Teva 2 g + 0.25 g can be administered either intramuscularly or by intravenous infusion (over 30 minutes), only by a doctor or nurse.
Intramuscular administration
Piperacillin and Tazobactam Teva 2 g + 0.25 g must be reconstituted with the vial of solvent supplied in the package, containing 4 ml of 0.5% monohydrate hydrochloride lidocaine solution.
The solvent vial containing lidocaine supplied in the package must be used only for intramuscular administration.
Do not exceed a dose of 2 g + 0.25 g of piperacillin/tazobactam per injection site.
For correct reconstitution, follow the procedure below:

  1. Shake the vial containing the lyophilisate to be reconstituted, so that the powder detaches from the bottom of the vial.
  2. Remove the flip-off plastic cap from the vial to expose the central portion of the rubber stopper and keep it (Fig. 1).
    Always avoid touching the central portion of the rubber stopper with your hands.
A hand holding a small glass vial with a cap, and an arrow indicating the direction towards the

Fig. 1
3) Using a syringe, withdraw the solvent containing lidocaine and inject it into the vial containing the lyophilisate.
4) Place the plastic cap over the rubber stopper to avoid touching the central portion with your fingers. Shake vigorously until the powder is completely dissolved. Under continuous shaking, reconstitution should be complete within 10 minutes (Fig. 2).

A hand holding a small medicine vial and gently shaking it with a rotational motion indicated by two curved arrows

Fig. 2
5) Let the resulting solution stand until the foam disappears and a clear solution is obtained. Ensure that no undissolved particles remain.
6) Remove the plastic cap and withdraw the solution with a 5 ml syringe for intramuscular administration.
After reconstitution, the solution must be administered immediately.
Unused solutions must be discarded.

Piperacillin and Tazobactam Teva 4 g + 0.5 g is administered by intravenous infusion (over 30 minutes).
Your doctor or healthcare provider will administer this medicine to you as an infusion (a drip over 30 minutes) into a vein. The dose of medicine administered depends on the reason for treatment, your age, and whether you have any kidney problems.

Adults and adolescents over 12 years of age
The usual dose is 4 g/0.5 g of piperacillin/tazobactam every 6–8 hours, administered into 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 body weight of piperacillin/tazobactam, every 8 hours, administered intravenously (directly into the bloodstream). The usual dose for children with low white blood cell counts is 80 mg/10 mg/kg body weight of piperacillin/tazobactam, every 6 hours, administered intravenously (directly into the bloodstream).
The doctor will calculate the dose based on the child's body weight; however, in no case will any individual dose exceed 4 g/0.5 g of Piperacillin and Tazobactam Teva.

Piperacillin and Tazobactam Teva will be administered until all signs of infection have completely disappeared (5–14 days).

Patients with kidney problems
Your doctor may need to reduce the dose of Piperacillin and Tazobactam Teva or the frequency of administration. The doctor may also perform blood tests to ensure that the prescribed dose is appropriate, especially if you are to receive this medicine for a prolonged period.

If you use more Piperacillin and Tazobactam Teva than you should
Since Piperacillin and Tazobactam Teva will be administered by a doctor or healthcare professional, it is unlikely that you will receive an incorrect dose. However, if adverse effects such as seizures occur, or if you think you have been given an excessive dose, inform your doctor immediately.

If you forget to use Piperacillin and Tazobactam Teva
If you think a dose of Piperacillin and Tazobactam Teva has not been administered, inform your doctor or healthcare provider immediately.

If you have any questions about the use of this product, consult your doctor or healthcare provider.

4. Possible side effects

Like all medicines, Piperacillin and Tazobactam Teva can cause side effects, although not
everyone experiences them.
If any of the side effects worsen, or if you notice any side effects not listed in this leaflet, inform your doctor or healthcare professional.
Serious side effects of Piperacillin and Tazobactam Teva include:

  • severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis), which initially appear as reddish spots or circular wheals, often with central blisters, on the trunk. Further symptoms include ulcers in the mouth, throat, nose, extremities, genitals, and conjunctivitis (red and swollen eyes). The skin rash may progress to widespread blistering or skin peeling, which can potentially be life-threatening; a skin condition (acute generalized exanthematous pustulosis) accompanied by fever, characterized by numerous small fluid-filled pustules within large areas of swollen and reddened skin;
  • severe, potentially fatal allergic reaction (drug reaction with eosinophilia and systemic symptoms) that may affect the skin and particularly other subcutaneous organs such as the kidneys and liver;
  • swelling of the face, lips, tongue, or other body parts;
  • shortness of breath, wheezing, or difficulty breathing;
  • severe rash, itching, or hives;
  • yellowing of the eyes or skin;
  • damage to blood cells (signs include: unexpected breathlessness, red or brown urine, nosebleeds, and appearance of bruises);
  • severe or persistent diarrhoea accompanied by fever or weakness;
  • unexpected bleeding, especially in patients taking anticoagulants such as warfarin.

If you experience any of the above side effects, consult your doctor immediately. For the frequency
of these reactions, refer to the information below.
The possible side effects are listed according to the following categories:
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Not known: frequency cannot be estimated from the available data

Very common side effects:

  • diarrhoea.

Common side effects:

  • fungal infection (candidiasis);
  • reduced number of platelets in the blood (thrombocytopenia);
  • reduced number of red blood cells (anaemia);
  • insomnia;
  • headache;
  • vomiting, nausea;
  • constipation;
  • indigestion (dyspepsia);
  • abdominal pain;
  • skin rash;
  • itching;
  • fever;
  • injection site reaction;
  • increased levels of certain enzymes in the blood (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase);
  • reduced total protein levels in the blood;
  • reduced albumin protein levels in the blood;
  • abnormal laboratory test (positive direct Coombs test);
  • increased muscle metabolism product in the blood (elevated serum creatinine);
  • increased blood urea levels;
  • prolonged activated partial thromboplastin time (a parameter used to assess the speed of blood clot formation).

Uncommon side effects:

  • reduced number of white blood cells (leucopenia);
  • low potassium levels in the blood (hypokalaemia);
  • seizures;
  • decreased blood pressure (hypotension);
  • inflammation of veins, felt as tenderness or redness in the affected area (thrombophlebitis, phlebitis);
  • hot flushes;
  • urticaria;
  • skin reactions with redness and skin lesions (erythema multiforme);
  • skin rash with papule formation (maculopapular rash);
  • joint pain (arthralgia) and muscle pain (myalgia);
  • chills;
  • low blood sugar (hypoglycaemia);
  • increased breakdown product of blood pigments (bilirubin);
  • prolonged prothrombin time (a parameter used to assess the speed of blood clot formation).

Rare side effects:

  • a specific type of colon infection (pseudomembranous colitis);
  • severe reduction in a specific type of white blood cells (agranulocytosis);
  • nosebleeds (epistaxis);
  • inflammation of the mucous membranes of the mouth (stomatitis);
  • detachment of the upper layer of skin over the entire body (toxic epidermal necrolysis).

Side effects with frequency not known (cannot be estimated from the available data):

  • reduced red blood cells, white blood cells, and platelets (pancytopenia);
  • reduced number of a specific type of white blood cells (neutropenia);
  • reduced red blood cells due to premature destruction (haemolytic anaemia);
  • significant increase in platelet count with a tendency towards thrombosis and bleeding (thrombocytosis);
  • increased number of a specific type of white blood cells (eosinophilia);
  • severe allergic reaction (anaphylactic/anaphylactoid reaction, including anaphylactic/anaphylactoid shock);
  • development of allergy (hypersensitivity);
  • delirium;
  • accumulation of eosinophils, a type of white blood cells, in the lungs (eosinophilic pneumonia);
  • jaundice (yellowing of the skin or whites of the eyes);
  • inflammation of the liver (hepatitis);
  • severe widespread allergic reaction with skin rash and blisters (Stevens-Johnson syndrome), severe allergic reaction affecting both the skin and other organs such as the kidneys and liver (DRESS: drug reaction with eosinophilia and systemic symptoms), widespread pustules accompanied by fever (AGEP: acute generalized exanthematous pustulosis), severe skin inflammations (exfoliative dermatitis, bullous dermatitis);
  • appearance of bruises and spots (purpura);
  • reduced kidney function and kidney problems (renal failure, tubulointerstitial nephritis);
  • prolonged bleeding time;
  • increased gamma-glutamyltransferase.

Piperacillin therapy has been associated with a higher incidence of fever and rash in patients
with cystic fibrosis.
Beta-lactam antibiotics, including piperacillin-tazobactam, may lead to manifestations of
encephalopathy and seizures.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Piperacillin and Tazobactam Teva

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 month.
Intact vials: do not store above 25°C.
For single use only. Discard any unused solution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Piperacillina e Tazobactam Teva contains
Piperacillina e Tazobactam Teva 2 g + 0.25 g/4 ml powder and solvent for injectable solution for intramuscular use
The active substances are 2.085 g of sodium piperacillin (equivalent to 2 g of piperacillin monohydrate) and 0.2683 g of sodium tazobactam (equivalent to 0.250 g of tazobactam).
The solvent vial contains: monohydrochloride lidocaine and water for injections (the solvent vial, containing monohydrochloride lidocaine, is for intramuscular use only).

Piperacillina e Tazobactam Teva 4 g + 0.5 g powder for infusion solution
The vial contains:
The active substances are 4.170 g of sodium piperacillin (equivalent to 4 g of piperacillin monohydrate) and 0.5366 g of sodium tazobactam (equivalent to 0.5 g of tazobactam).

Description of the appearance of Piperacillina e Tazobactam Teva and contents of the pack
Piperacillina e Tazobactam Teva 2 g + 0.25 g/4 ml powder and solvent for injectable solution for intramuscular use
White to off-white powder, supplied in one vial + one 20 mg/4 ml solvent vial of monohydrochloride lidocaine, for intramuscular use only.
Pack contains 1 vial + 1 solvent vial.

Piperacillina e Tazobactam Teva 4 g + 0.5 g powder for infusion solution
White to off-white powder, supplied in one vial.
Pack contains 1 vial.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Teva Italia S.r.l. – Piazzale Luigi Cadorna, 4 - 20123 - Milan
Manufacturer
Mitim S.r.l. – Via Cacciamali, 34-38, 25125 Brescia (BS)

This patient information leaflet was last approved on

The following information is intended for healthcare professionals only:
Instructions for use
Piperacillina e Tazobactam Teva must be administered by intravenous infusion (a 30-minute infusion).

Intravenous administration
Must be performed only by healthcare personnel.
Reconstitute the product with the volume of solvent indicated in the table below, using one of the compatible solutions listed. Shake until dissolved; under continuous agitation, reconstitution should be complete within 5–10 minutes.

Vial content (piperacillin/tazobactam) _________________ Volume of solvent to add
Piperacillina e Tazobactam Teva 2 g + 0.25 g 10 ml
Piperacillina e Tazobactam Teva 4 g + 0.5 g 20 ml

Compatible solutions

  • Water for injections
  • Sodium chloride 0.9% solution
  • Sodium chloride solution with benzyl alcohol
  • Sodium chloride solution with parabens
  • Dextrose 5% solution

Shake the vial containing the lyophilized powder to detach the powder from the bottom of the vial. Using a syringe, draw up an appropriate solvent and inject it into the vial containing the lyophilized powder. Shake vigorously until the powder is completely dissolved. Under continuous agitation, reconstitution should be complete within 10 minutes. Allow the resulting solution to stand until foam disappears and a clear solution is obtained. Ensure that no undissolved particles remain before withdrawing the solution with an appropriate syringe. If reconstitution has been performed as indicated, the solution withdrawn will contain the amount of piperacillin and tazobactam stated on the label. The reconstituted solution may be further diluted to the desired volume (50–150 ml) using one of the following compatible diluents for intravenous administration:

  • Water for injections (the maximum recommended volume of water for injections is 50 ml per dose)
  • Sodium chloride 0.9% solution
  • Glucose 5% solution
  • Dextran 6% in sodium chloride solution

Co-administration with aminoglycosides
Due to the in vitro inactivation of aminoglycosides by beta-lactam antibiotics, Piperacillina e Tazobactam Teva and aminoglycosides should be administered separately. When concomitant therapy with aminoglycosides is indicated, Piperacillina e Tazobactam Teva and the aminoglycoside must be reconstituted and diluted separately.