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PACKAGE LEAFLET: INFORMATION FOR THE USER

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

(piperacillin and tazobactam)

Read all of this leaflet carefully before you start using this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

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

2.    Before you are given Piperacillin Tazobactam.

3.    How Piperacillin Tazobactam is given.

4.    Possible side effects.

5.    How to store Piperacillin Tazobactam.

6.    Further information.

1.    WHAT PIPERACILLIN TAZOBACTAM IS AND WHAT IT IS USED FOR

Piperacillin belongs to the group of medicines known as 'broad-spectrum penicillin antibiotics'. It can kill many kinds 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 Tazobactam is used in adults and adolescents to treat bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin or blood. Piperacillin Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

Piperacillin Tazobactam is used in children aged 2-12 years to treat infections of the abdomen such as appendicitis, peritonitis (infection of the fluid and lining of the abdominal organs), and gallbladder (biliary) infections. Piperacillin Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

In certain serious infections, your doctor may consider using Piperacillin Tazobactam in combination with other antibiotics.

2.    BEFORE YOU ARE GIVEN PIPERACILLIN TAZOBACTAM Do not use Piperacillin Tazobactam:

•    if you are allergic (hypersensitive) to piperacillin or tazobactam or any of the other ingredients of Piperacillin Tazobactam.

•    if you are allergic (hypersensitive) to antibiotics known as penicillins, cephalosporins or other beta-lactamase inhibitors, as you may be allergic to Piperacillin Tazobactam.

Take special care with Piperacillin Tazobactam:

•    if you have allergies. If you have several allergies, make sure you tell your doctor or other healthcare professional before receiving this product

•    if you are suffering from diarrhoea before, or if you develop diarrhoea during or after your treatment. In this case, make sure you tell your doctor or other healthcare professional immediately. Do not take any medicine for the diarrhoea without first checking with your doctor

•    if you have low levels of potassium in your blood. Your doctor may want to check your kidneys before you take this medicine and may perform regular blood tests during treatment

•    if you have kidney or liver problems, or are receiving haemodialysis. Your doctor may want to check your kidneys before you take this medicine, and may perform regular blood tests during treatment

•    if you are taking certain medicines (called anticoagulants) to avoid an excess of blood clotting (see also 'Using other medicines' in this leaflet) or any unexpected bleeding occurs during the treatment. In this case, you should inform your doctor or other healthcare professional immediately

•    if you develop convulsions during the treatment. In this case, you should inform your doctor or other healthcare professional

•    if you think you developed a new or worsening infection. In this case, you should inform your doctor or other healthcare professional.

Children below 2 years

Piperacillin / tazobactam is not recommended for use in children below the age of 2 years due to insufficient data on safety and effectiveness.

Using other medicines

Please tell your doctor or other healthcare professional if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Some medicines may interact with piperacillin and tazobactam.

These include:

•    medicine for gout (probenecid). This can increase the time it takes for piperacillin and tazobactam to leave your body

•    medicines to thin your blood or to treat blood clots (e.g. heparin, warfarin or aspirin)

•    medicines used to relax your muscles during surgery. Tell your doctor if you are going to have a general anaesthetic

•    methotrexate (medicine used to treat cancer, arthritis or psoriasis). Piperacillin and tazobactam can increase the time it takes for methotrexate to leave your body

•    medicines that reduce the level of potassium in your blood (e.g. tablets enhancing urination or some medicines for cancer)

•    medicines containing the other antibiotics tobramycin or gentamycin. Tell your doctor if you have kidney problems.

Effect on laboratory tests

Tell the doctor or laboratory staff that you are taking Piperacillin Tazobactam if you have to provide a blood or urine sample.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are trying to become pregnant, tell your doctor or other healthcare professional before receiving this product. Your doctor will decide if Piperacillin Tazobactam is right for you. Piperacillin and tazobactam can pass to a baby in the womb or through breast milk. If you are breast-feeding, your doctor will decide if Piperacillin Tazobactam is right for you.

Driving and using machines

The use of Piperacillin Tazobactam is not expected to affect the ability to drive or use machines.

Important information about some of the ingredients of Piperacillin Tazobactam

Piperacillin Tazobactam 2 g / 0.25 g contains 4.7 mmol (108 mg) of sodium per vial of powder for solution for infusion. This should be taken into consideration if you are on a controlled-sodium diet.

3. HOW PIPERACILLIN TAZOBACTAM IS GIVEN

Your doctor or other healthcare professional will give you this medicine through an infusion (a drip for 30 minutes) into one of your veins. The dose of medicine given to you depends on what you are being treated for, your age, and whether or not you have kidney problems.

_ ____________________

The following information is intended for medical or healthcare professionals only:

Piperacillin Tazobactam 2 g/0.25 g, Powder for solution for infusion

Instructions for use - Piperacillin Tazobactam will be given by intravenous infusion (a drip for 30 minutes).

Intravenous use - Reconstitute each vial with the volume of solvent shown in the table below, using one of the compatible solvents for reconstitution. Swirl until dissolved. When swirled constantly, reconstitution generally occurs within 2 to 3 minutes (for details on handling, please see below).

Content of vial_Volume of solvent* to be added to vial

2 g / 0.25 g (2 g piperacillin and 0.25 g tazobactam)    10 ml

4 g / 0.50 g (4 g piperacillin and 0.5 g tazobactam)    20 ml

*Compatible solvents for reconstitution:

•    0.9% (9 mg/ml) sodium chloride solution for injection

•    Sterile water for injections⁽¹⁾

•    Glucose 5%

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

The reconstituted solutions should be withdrawn from the vial by syringe. When reconstituted as directed, the vial contents withdrawn by syringe will provide the labelled amount of piperacillin and tazobactam.

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

•    0.9% (9 mg/ml) sodium chloride solution for injection

•    Glucose 5%

•    Dextrose 5% in water

Adults and adolescents aged 12 years or older

The usual dose is 4 g / 0.5 g of piperacillin / tazobactam given every 6-8 hours, which is given into one of your veins (directly into the blood stream).

Children aged 2 to 12 years

The usual dose for children with abdominal infections is 100 mg / 12.5 mg / kg of body weight of piperacillin / tazobactam given every 8 hours into one of your veins (directly into the blood stream). The usual dose for children with low white blood cell counts is 80 mg / 10 mg / kg of body weight of piperacillin / tazobactam given every 6 hours into one of your veins (directly into the blood stream). Your doctor will calculate the dose depending on your child's weight but the daily dose will not exceed 4 g / 0.5 g of Piperacillin Tazobactam.

You will be given Piperacillin Tazobactam until the sign of infection has gone completely (5 to 14 days). Patients with kidney problems

Your doctor may need to reduce the dose of Piperacillin Tazobactam or how often you are given it. Your doctor may also want to test your blood to make sure that your treatment is at the right dose, especially if you have to take this medicine for a long time.

If you receive more Piperacillin Tazobactam than you should

As you will receive Piperacillin Tazobactam from a doctor or other healthcare professional, you are unlikely to be given the wrong dose. However, if you experience side effects, such as convulsions, or think you have been given too much, tell your doctor immediately.

If you miss a dose of Piperacillin Tazobactam

If you think you have not been given a dose of Piperacillin Tazobactam, tell your doctor or other healthcare professional immediately.

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

4.    POSSIBLE SIDE EFFECTS

Like all medicines, Piperacillin Tazobactam can cause side effects, although not everybody gets them. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or other healthcare professional.

The serious side effects of Piperacillin Tazobactam are:

•    swelling of the face, lips, tongue or other parts of the body

•    shortness of breath, wheezing or trouble breathing

•    severe rash, itching or hives on the skin

•    yellowing of the eyes or skin

•    damage to blood cells (the signs include: being breathless when you do not expect it, red or brown urine, nosebleeds and bruising).

If you notice any of the above, see a doctor straight away.

For frequency of these reactions, refer to the information below.

Possible side effects are listed according to the following categories:

•    common: affects 1 to 10 users in 100

•    uncommon: affects 1 to 10 users in 1,000

•    rare: affects 1 to 10 users in 10,000

•    very rare: affects less than 1 user in 10,000.

Common side effects: • diarrhoea, vomiting, nausea • skin rashes.

Uncommon side effects: • thrush • (abnormal) decrease in white blood cells (leukopenia, neutropenia) and platelets (thrombocytopenia) • allergic reaction • headache, sleeplessness • low blood pressure, inflammation of the veins (felt as tenderness or redness in the affected area) • jaundice (yellow staining of the skin or whites of the eyes), inflammation of the mucous lining of the mouth, constipation, indigestion, stomach upset • increase of certain enzymes in the blood (alanine aminotransferase increased, aspartate aminotransferase increased) • itching, nettle rash • increase of muscle metabolism product in the blood (blood creatinine increased) • fever, injection site reaction

•    yeast infection (candidal superinfection).

Rare side effects: • (abnormal) decrease of red blood cells or blood pigment / haemoglobin, (abnormal) decrease of red blood cells due to premature breakdown (degradation) (haemolytic anaemia), small spot bruising (purpura), bleeding of the nose (epistaxis) and bleeding time prolonged, (abnormal) increase of a specific type of white blood cells (eosinophilia) • severe allergic reaction (anaphylactic/anaphylactoid reaction, including shock) • flushed red skin • a certain form of infection of the colon (pseudomembranous colitis), abdominal pain • inflammation of the liver (hepatitis), increase of a blood pigments breakdown product (bilirubin), increase of certain enzymes in the blood (blood alkaline phosphatase increased, gamma-glutamyltransferase increased)

•    skin reactions with redness and formation of skin lesions (exanthema, erythema multiforme), skin reactions with blistering (bullous dermatitis) • joint and muscle pain • poor kidney functions and kidney problems • rigors chill / rigidity.

Very rare side effects: • severe decrease of granular white blood cells (agranulocytosis), severe decrease of red blood cells, white blood cells and platelets (pancytopenia) • prolonged time for blood clot formation (prolonged partial thromboplastin time, prothrombin time prolonged), abnormal lab test (positive direct Coombs), increase of platelets (thrombocythaemia) • decrease of potassium in the blood (hypokalaemia), decrease of blood sugar (glucose), decrease of the blood protein albumin, decrease of blood total protein • detachment of the top layer of the skin all over the body (toxic epidermal necrolysis), serious bodywide allergic reaction with skin and mucous lining rashes and various skin eruptions (Stevens-Johnson Syndrome) • blood urea nitrogen increased.

Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

5.    HOW TO STORE PIPERACILLIN TAZOBACTAM

Keep out of the reach and sight of children.

Do not use Piperacillin Tazobactam after the expiry date which is stated on the carton and vial after 'EXP'. The expiry date refers to the last day of that month.

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. These measures will help to protect the environment.

6.    FURTHER INFORMATION

What Piperacillin Tazobactam contains

The active substances are piperacillin and tazobactam.

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

There are no other ingredients.

What Piperacillin Tazobactam looks like and contents of the pack

Piperacillin Tazobactam is a white to off-white powder supplied in a vial. Packs containing 1,5, 10,

12 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom.

Manufacturer:

Laboratorio Pharmaceutico C.T.S.r.l. - Via Dante Alighieri, 71 - 18038 SANREMO - IM - Italy.

Mitim S.r.l. Via Rodi n°27, 25126 Brescia, Italy.

Detailed information on this medicine is available on the web site of the MHRA: http://www.mhra.gov.uk/index.htm

This leaflet was revised in: March 2012    EYZ I.107214-A    10003807

_ *•&»______________________

Incompatibilities - Whenever Piperacillin Tazobactam is used concurrently with another antibiotic (e.g. aminoglycosides), the substances must be administered separately. The mixing of beta-lactam antibiotics with aminoglycosides, in vitro, can result in substantial inactivation of the aminoglycoside).

Piperacillin Tazobactam should not be mixed with other substances in a syringe or infusion bottle since compatibility has not been established.

Because of chemical instability, Piperacillin Tazobactam should not be used with solutions containing sodium bicarbonate.

Lactated Ringer's (Hartmann's) solution is not compatible with Piperacillin Tazobactam.

Piperacillin Tazobactam should not be added to blood products or albumin hydrolysates.

Co-administration of Piperacillin Tazobactam with aminoglycosides

Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, Piperacillin Tazobactam and the aminoglycoside are recommended for separate administration. Piperacillin Tazobactam and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated.

Piperacillin Tazobactam should be administered through an infusion set separately from any other drugs unless compatibility is proven.

Special precautions for storage - Before first opening: Do not store above 25°C.

After reconstitution/dilution: To reduce the risk of microbial contamination, reconstituted/diluted solutions should be used immediately. If not used immediately, in use storage times and conditions prior to administration are the responsibility of the user.