TAZOCIN 2G/0.25G POWDER FOR SOLUTION FOR INFUSION

The following information is intended for medical or healthcare professionals only: Instructions for use TAZOCIN will be given by intravenous infusion (a drip for 30minutes). 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 5 to 10minutes (details for handling, please see below). Content of vial 2 g / 0.25g (2g piperacillin and 0.25g tazobactam) 4 g / 0.50g (4g piperacillin and 0.5g tazobactam) 10ml 20ml Volume of solvent* to be added to vial

PACKAGE LEAFLET: INFORMATION FOR THE USER Tazocin 2g / 0.25gpowder for solution for infusion Tazocin 4g / 0.5gpowder for solution for infusion piperacillin / 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 TAZOCIN is and what it is used for 2. Before you use TAZOCIN 3. How to use TAZOCIN 4. Possible side effects 5. How to store TAZOCIN 6. Further information 1. WHAT TAZOCIN 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. TAZOCIN 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. TAZOCIN may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections).

TAZOCIN 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. TAZOCIN 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 TAZOCIN in combination with other antibiotics. 2. BEFORE YOU USE TAZOCIN Do not use TAZOCIN - if you are allergic (hypersensitive) to piperacillin or tazobactam or any of the other ingredients of TAZOCIN. - if you are allergic (hypersensitive) to antibiotics known as penicillins, cephalosporins or other beta-lactamase inhibitors, as you may be allergic to TAZOCIN. Take special care with TAZOCIN - 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 d haemo ialysis. 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.

* Compatible solvents for reconstitution: - 0.9% (9mg/ml) sodium chloride solution for injection - Sterile water for injection(1) - Glucose 5% (1) Maximum recommended volume of sterile water for injection per dose is 50ml. 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. 50ml to 150ml) with one of the following compatible solvents: - 0.9% (9mg/ml) sodium chloride solution for injection - Glucose 5% - Dextran 6% in 0.9% sodium chloride - Lactated Ringers injection - Hartmanns solution - Ringers acetate - Ringers acetate/malate Incompatibilities Whenever TAZOCIN 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. However, amikacin and gentamicin were determined to be compatible
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- 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 TAZOCIN 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 TAZOCIN 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 TAZOCIN is right for you. 8930066 RA Laetus 43

Driving and using machines The use of TAZOCIN is not expected to affect the ability to drive or use machines. Important information about some of the ingredients of TAZOCIN TAZOCIN 2 g / 0.25 g contains 5.58 mmol (128 mg) of sodium. TAZOCIN 4 g / 0.5 g contains 11.16 mmol (256 mg) of sodium. This should be taken into consideration if you are on a controlled-sodium diet. 3. HOW TO USE TAZOCIN Your doctor or other healthcare professional will give you this medicine through an infusion (a drip for 30 minutes) into one of your veins. Dosage 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. 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 childs weight but the daily dose will not exceed 4 g / 0.5 g of TAZOCIN. You will be given TAZOCIN 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 TAZOCIN 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.
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If you receive more TAZOCIN than you should As you will receive TAZOCIN 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 TAZOCIN If you think you have not been given a dose of TAZOCIN, 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, TAZOCIN can cause side effects, although not everybody gets them. See a doctor immediately if you experience any of these potentially serious side effects of TAZOCIN: The serious side effects of TAZOCIN 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) severe or persistent diarrhoea accompanied by a fever or weakness unexpected bleeding, particularly if you are taking anti coagulants such as warfarin. If any of the following side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or other healthcare professional. Possible side effects are listed according to the following frequencies: - 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 aminotrans ferase 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 TAZOCIN Keep out of the reach and sight of children. Do not use TAZOCIN 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 25C. For single use only. Discard any unused solution. Medicines should not be disposed of via wastewater or house old waste. Ask your pharmacist how to dispose of h medicines no longer required. These measures will help to protect the environment. 6. FURTHER INFORMATION What TAZOCIN 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).

Each vial contains 4 g piperacillin (as sodium salt) and 0.5 g tazobactam (as sodium salt). - The other ingredients are citric acid monohydrate and edetate disodium (EDTA). What TAZOCIN looks like and contents of the pack TAZOCIN 2 g / 0.25 g is a white to off-white powder supplied in a vial. Packs containing 1, 5, 10, 12 or 25 vials. TAZOCIN 4 g / 0.5 g is a white to off-white powder supplied in a vial. Packs containing 1, 5, 10, 12 or 25 vials. Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer UK MA Holder: Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom. Ireland MA Holder: Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24, Ireland Malta MA Holder: Pfizer Hellas S.A. 243, Messoghion Avenue, 154 51 N. Psychiko, Greece Manufacturer: Wyeth Lederle S.p.A. Via Franco Gorgone, Zona Industriale 95100 Catania Italy This leaflet was last approved in 01/2012 Ref: TA 4_0 .

with TAZOCIN in vitro in certain diluents at specific concentrations (see Co-administration of TAZOCIN with aminoglycosides below). TAZOCIN should not be mixed with other substances in a syringe or infusion bottle since compatibility has not been established. Because of chemical instability, TAZOCIN should not be used with solutions containing only sodium bicarbonate. TAZOCIN is compatible with lactated Ringers solution and for co-administration via a Y-site. TAZOCIN should not be added to blood products or albumin hydrolysates. Co-administration of TAZOCIN with aminoglycosides Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, TAZOCIN and the aminoglycoside are recommended for separate administration. TAZOCIN and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated. In circumstances where co-administration is recomended, TAZOCIN is compatible for simultaneous coadministration via Ysite infusion only with the following aminoglycosides under the following conditions:
Aminoglycoside TAZOCIN Dose 2 g / 0.25 g 4 g / 0.5 g TAZOCIN AminoglycoDiluent side volume concentration (ml) range* (mg/ml) 50, 100, 150 1.75 7.5 Acceptable diluents

Amikacin

0.9% sodium chloride or 5% glucose

Gentamicin

2 g / 0.25 g 4 g / 0.5 g

50, 100, 150

0.7 3.32

0.9% sodium chloride or 5% glucose

This leaflet can be made available in large print, audio or Braille on request. Contact 0800 198 5000 to request this, quoting one of the following numbers: 00057/1293 or 00057/1294.

* The dose of aminoglycoside should be based on patient weight, status of infection (serious or lifethreatening) and renal function (creatinine clearance). Compatibility of TAZOCIN with other aminoglycosides has not been established. Only the concentration and diluents for amikacin and gentamicin with the dose of TAZOCIN listed in the above table have been established as compatible for coadministration via Ysite infusion. Simultaneous co-administration via Ysite in any manner other than listed above may result in inactivation of the aminoglycoside by TAZOCIN.