Piperacillin and tazobactam Aurobindo: detailed information

Package leaflet: Information for the user

Piperacillin and Tazobactam Aurobindo 2 g/0.25 g powder for solution for infusion, 4 g/0.5 g powder for solution for infusion

Generic medicine
Please read all of this leaflet carefully before taking this medicine because 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 give it to other people, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

What Piperacillin and Tazobactam Aurobindo is and what it is used for
What you need to know before taking Piperacillin and Tazobactam Aurobindo
How to take Piperacillin and Tazobactam Aurobindo
Possible side effects
How to store Piperacillin and Tazobactam Aurobindo
Contents of the pack and other information

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

Piperacillin belongs to a group of antibiotic medicines known as "broad-spectrum penicillins", which can
kill many types of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects
of piperacillin. This means that when piperacillin and tazobactam are given together, more types of bacteria
are killed.
Piperacillin and Tazobactam Aurobindo 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 Aurobindo may be used for the
treatment of bacterial infections in patients with low white blood cell counts (reduced resistance to
infections).
Piperacillin and Tazobactam Aurobindo 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 Aurobindo may be used for the
treatment of bacterial infections in patients with low white blood cell counts in the blood
(reduced resistance to infections).
In certain severe infections, your doctor may consider using Piperacillin and Tazobactam Aurobindo in
combination with other antibiotics.

2. What you need to know before taking Piperacillin and Tazobactam Aurobindo

Do not use Piperacillin and Tazobactam Aurobindo

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 known as penicillins, cephalosporins, or other beta-lactamase inhibitors, as you may also be allergic to Piperacillin and Tazobactam Aurobindo.

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

if you have allergies. If you have multiple allergies, inform your doctor or healthcare provider before receiving this medicine;
if you have had diarrhoea before, 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 your blood. Your doctor may decide to check your kidney function before administering this medicine and may prescribe periodic blood tests during treatment;
if you have kidney or liver problems, or if you are undergoing haemodialysis. Your doctor may decide 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 at the same time as piperacillin/tazobactam, as this may increase the risk of kidney damage (see also Other medicines and Piperacillin and Tazobactam Aurobindo in this leaflet);
if you are taking certain medicines (called anticoagulants) to prevent excessive blood clotting (see also Other medicines and Piperacillin and Tazobactam Aurobindo in this leaflet), or if unexpected bleeding occurs during treatment. In this case, you must inform your doctor or healthcare provider immediately;
if you develop seizures during treatment. In this case, inform your doctor or healthcare provider;
if you suspect you have developed a new infection or if your infection has worsened. In this case, inform your doctor or healthcare provider.

Haemophagocytic lymphohistiocytosis
Cases of a disease in which the immune system produces an abnormally high number 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 or glands, feeling weak, mental confusion, shortness of breath, bruising, or rash, contact your doctor 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 Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without 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 to treat blood clots (e.g. heparin, warfarin, or aspirin).
Medicines used to relax muscles during surgery. Inform your doctor if you are due to undergo 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. tablets that increase urine production or certain cancer medicines).
Medicines containing the other antibiotics tobramycin, gentamicin, or vancomycin. Inform your doctor if you have kidney problems. Taking piperacillin/tazobactam together with vancomycin 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 Aurobindo if you are required to provide a blood or urine sample.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. Your doctor will decide whether Piperacillin and Tazobactam Aurobindo is suitable 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 Aurobindo is suitable for you.

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

Piperacillin and Tazobactam Aurobindo contains sodium
Piperacillin and Tazobactam Aurobindo 2 g/0.25 g
This medicine contains 108 mg of sodium (a main component of table salt) per vial.
This corresponds to 5.4% of the maximum recommended daily dietary intake for an adult.
Piperacillin and Tazobactam Aurobindo 4 g/0.5 g
This medicine contains 216 mg of sodium (a main component of table salt) per vial.
This corresponds to 10.8% of the maximum recommended daily dietary intake for an adult.
This should be taken into consideration in patients on a low-sodium diet.

3. How to take Piperacillin and Tazobactam Aurobindo

Your doctor or healthcare professional will administer this medicine to you as an infusion (an intravenous drip) into a vein over 30 minutes.
Dosage
The dose of medicine given 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 piperacillin/tazobactam every 6–8 hours, administered intravenously (directly into the bloodstream).
Children aged 2 to 12 years
The recommended 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, but in any case, each single dose will not exceed 4 g/0.5 g of Piperacillin and Tazobactam Aurobindo.
Piperacillin and Tazobactam Aurobindo 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 or frequency of administration of Piperacillin and Tazobactam Aurobindo. Your 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 receive more Piperacillin and Tazobactam Aurobindo than you should
Since Piperacillin and Tazobactam Aurobindo is administered by a doctor or healthcare professional, it is unlikely that you will receive an incorrect dose. However, if side effects such as seizures occur, or if you think you have been given too much medicine, inform your doctor immediately.
If you miss a dose of Piperacillin and Tazobactam Aurobindo
If you think a dose of Piperacillin and Tazobactam Aurobindo has not been administered, inform your doctor or healthcare professional immediately.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following potentially serious side effects of Piperacillin and Tazobactam Aurobindo.
Serious side effects of Piperacillin and Tazobactam Aurobindo include:

severe skin reactions [(Stevens-Johnson syndrome, bullous dermatitis (not known), exfoliative dermatitis (not known), toxic epidermal necrolysis (rare)] which initially present as reddish patches or circular blisters often with central blisters on the trunk. Further signs include ulcers in the mouth, throat, nose, extremities, genitals and conjunctivitis (red and swollen eyes). The rash may progress to widespread blistering or peeling of the skin which can potentially be life-threatening;
a severe, potentially fatal allergic reaction (drug reaction with eosinophilia and systemic symptoms) which may involve the skin and especially other internal organs such as the kidney and liver;
a skin condition (generalized exanthematous pustulosis) accompanied by fever, consisting of numerous small fluid-filled pustules within 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 skin rash (common);
yellowing of the eyes or skin (not known);
blood cell damage [signs include: unexpected breathlessness, red or brown urine (not known), nosebleeds (rare), appearance of bruising with small red spots (not known), severe decrease in white blood cells (rare)];
severe or persistent diarrhoea accompanied by fever or weakness (rare).

If any of the following side effects become severe, or if you notice any side effects not listed in this leaflet, inform your doctor or healthcare professional.
Very common side effects (may affect more than 1 in 10 people):

diarrhoea.
Common side effects (may affect up to 1 in 10 people):
fungal infections;
reduction in platelets, reduction in red blood cells or blood pigment/haemoglobin, abnormal laboratory tests (positive direct Coombs test), prolonged bleeding time (prolonged activated partial thromboplastin time);
reduction in blood proteins;
headache, insomnia;
abdominal pain, vomiting, nausea, constipation, stomach upset;
increased liver enzymes in the blood;
skin rash, itching;
abnormal blood tests for kidney function;
fever, injection site reaction.

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

reduction in white blood cells (leucopenia), prolonged blood clotting time (prolonged prothrombin time);
low potassium levels in the blood, decreased blood sugar;
seizures (epilepsy), observed in patients receiving high doses or with kidney problems;
low blood pressure, inflammation of veins (felt as tenderness or redness in the affected area), skin redness;
increased levels of a breakdown product of blood pigments (bilirubin);
skin reactions with redness, skin lesion formation, hives;
joint and muscle pain;
chills.

Rare side effects (may affect up to 1 in 1,000 people):

severe reduction in white blood cells (agranulocytosis), nosebleeds;
serious infection of the colon, inflammation of the mucous membranes of the mouth;
detachment of the upper layer of skin all over the body (toxic epidermal necrolysis).

Side effects with unknown frequency (frequency cannot be determined from available data):

severe reduction in red blood cells, white blood cells and platelets (pancytopenia), reduction in white blood cells (neutropenia), reduction in red blood cells due to breakdown or premature destruction (haemolytic anaemia), appearance of bruising with small spots, prolonged bleeding time, increased platelets, increase in a specific type of white blood cell (eosinophilia);
allergic reaction and severe allergic reaction;
inflammation of the liver, yellowing of the skin or whites of the eyes;
severe, widespread allergic reaction affecting the skin and mucous membranes, with rash, blisters and various skin eruptions (Stevens-Johnson syndrome), severe allergic condition affecting the skin and other organs such as the kidney and liver (drug reaction with eosinophilia and systemic symptoms), numerous small fluid-filled blisters within large areas of swollen and reddened skin accompanied by fever (generalized exanthematous pustulosis), skin reactions with blisters (bullous dermatitis);
reduced kidney function and kidney problems;
a form of lung disease in which eosinophils (a type of white blood cell) appear in increased numbers in the lungs (eosinophilic pneumonia);
acute disorientation and confusion (delirium). 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 signs of altered brain function (encephalopathy) and seizures.
Reporting of side effects
If you experience any side effects, 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 https://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 Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the vials after
EXP. The expiry date refers to the last day of that month.
Powder:
Unopened vial: Store below 25°C.
For single use only.
Discard any unused solution.
Reconstituted/diluted solutions of the medicinal product are physically compatible and chemically stable for
a period of 24 hours at controlled room temperature (25°C) and for 48 hours at 2–8°C.
From a microbiological standpoint, reconstituted and diluted solutions should be used immediately. If not used
immediately, the duration and conditions of storage in use are the responsibility of the user and normally should
not exceed 24 hours at 2–8°C, unless reconstitution and dilution have taken place under validated, controlled,
aseptic conditions.
Do not dispose of any medicine 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 Aurobindo contains
The active substances are piperacillin and tazobactam.
Each vial contains sodium piperacillin equivalent to 2 g of piperacillin and sodium tazobactam
equivalent to 0.25 g of tazobactam.
Each vial contains sodium piperacillin equivalent to 4 g of piperacillin and sodium tazobactam
equivalent to 0.5 g of tazobactam.
There are no other components.

Description of the appearance of Piperacillina e Tazobactam Aurobindo and contents of the pack
Powder for solution for infusion.
White to off-white powder.
Piperacillina e Tazobactam Aurobindo is available in packs of 1, 10 or 12 vials, contained in a
package with a leaflet.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront,
Floriana FRN 1914, Malta

Manufacturer
Milpharm Limited
Ares, Odyssey Business Park
West End Road
South Ruislip HA4 6QD
United Kingdom
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

The following information is intended exclusively for physicians or healthcare professionals:
Piperacillina e Tazobactam Aurobindo 2 g/0.25 g
Piperacillina e Tazobactam Aurobindo 4 g/0.5 g
powder for solution for infusion

This is an extract from the Summary of Product Characteristics, intended to facilitate the
administration of Piperacillina e Tazobactam Aurobindo. Before deciding on the appropriateness of use
in a particular patient, the prescribing physician must be familiar with the full content of the SmPC.
For slow intravenous infusion.
Incompatibilities with diluents or other medicinal products

RINGER LACTATE SOLUTION (HARTMANN'S) IS NOT COMPATIBLE WITH PIPERACILLIN AND TAZOBACTAM AUROBINDO.
WHEN PIPERACILLIN AND TAZOBACTAM AUROBINDO IS USED CONCOMITANTLY WITH ANOTHER ANTIBIOTIC (E.G. AMINOGLYCOSIDES), PIPERACILLIN AND TAZOBACTAM AUROBINDO MUST BE ADMINISTERED SEPARATELY. MIXING PIPERACILLIN AND TAZOBACTAM AUROBINDO WITH AN AMINOGLYCOSIDE IN VITRO MAY RESULT IN INACTIVATION OF THE AMINOGLYCOSIDE.
PIPERACILLIN AND TAZOBACTAM AUROBINDO MUST NOT BE MIXED WITH OTHER DRUGS IN A SYRINGE OR INFUSION VIAL AS COMPATIBILITY HAS NOT BEEN ESTABLISHED.
DUE TO CHEMICAL INSTABILITY, PIPERACILLIN AND TAZOBACTAM AUROBINDO MUST NOT BE USED IN SOLUTIONS CONTAINING SODIUM BICARBONATE.
PIPERACILLIN AND TAZOBACTAM AUROBINDO MUST NOT BE ADDED TO BLOOD PRODUCTS OR ALBUMIN HYDROLYSATES.

INSTRUCTIONS FOR USE, HANDLING AND DISPOSAL
Reconstitution/dilution must be performed under aseptic conditions. Prior to administration, the
solution should be visually inspected for particulate matter and discoloration. The solution should be used only if it is clear and free of particles.

Instructions for inserting the needle into the rubber stopper:
To avoid coring of the stopper, it is recommended to use a needle with an outer diameter less than or equal to 0.8 mm when piercing the rubber stopper.
The needle should be inserted only in the center of the rubber stopper and in a vertical direction.

For single use only. Any unused solution must be discarded.
Unused medicines and waste materials derived from such medicines must be disposed of in accordance with local regulations.

Sterile diluents for preparation of reconstituted solution:

sterile water for injection
sodium chloride 9 mg/ml (0.9%) in water for injection
glucose 50 mg/ml (5%) in water for injection
glucose (5%) in sodium chloride (0.9%) solution

Instructions for dilution (for intravenous infusion)
Each vial of Piperacillina e Tazobactam Aurobindo 2 g/0.25 g must be reconstituted with 10 ml of one of the diluents listed above.
Each vial of Piperacillina e Tazobactam Aurobindo 4 g/0.5 g must be reconstituted with 20 ml of one of the diluents listed above.
Shake with rotational movement until dissolved.

The reconstituted solution may be further diluted to a concentration range of 13.33/1.67 mg/ml to 80/10 mg/ml using the following diluents:

sterile water for injection
sodium chloride 9 mg/ml (0.9%) for injection
glucose 50 mg/ml (5%) in water
glucose 5% in 0.9% sodium chloride solution

SPECIAL PRECAUTIONS FOR STORAGE
Unopened vial: Store below 25°C.
Reconstituted/diluted drug solutions are physically compatible and chemically stable for 24 hours at controlled room temperature (25°C) and for 48 hours at 2–8°C.
From a microbiological standpoint, reconstituted and diluted solutions should be used immediately. If not used immediately, the duration and conditions of storage in use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless reconstitution and dilution have been carried out under validated, controlled aseptic conditions.