Consumer medicine information

Tazopip Powder for Injection

Piperacillin; Tazobactam

BRAND INFORMATION

Brand name

Tazopip

Active ingredient

Piperacillin; Tazobactam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tazopip Powder for Injection.

What is in this leaflet

This leaflet answers some common questions about TAZOPIP.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking TAZOPIP against the benefits expected for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What TAZOPIP is used for

TAZOPIP contains the active ingredients piperacillin and tazobactam. This medicine belongs to a group of medicines called antibiotics called penicillins. It works by killing bacteria.

Piperacillin is an antibiotic that kills many types of bacteria. Tazobactam belongs in the penicillin group but does not have activity against bacteria. It helps piperacillin to overcome bacteria which have become resistant to piperacillin.

This medicine is active against bacteria which cause serious infections such as:

  • Chest infections
  • Urine infections
  • Stomach infections
  • Skin infections
  • Gynaecological infections
  • Septicaemia (blood poisoning).

TAZOPIP is also used to treat many other infections.

In hospitalised children aged 2 to 12 years, TAZOPIP is used to treat serious infections in the abdomen.

TAZOPIP is not recommended to treat abdominal infections in children under 2 years.

TAZOPIP will not work against infections caused by viruses such as cold or flu.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

This medicine is not addictive.

Before you are given TAZOPIP

When you must not receive TAZOPIP

Do not receive TAZOPIP if you have an allergy to:

  • any medicine containing piperacillin, tazobactam, or any other penicillin antibiotics
  • any antibiotics in the cephalosporin group
  • any medicines called beta-lactamase inhibitors.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath.
  • wheezing or difficulty breathing.
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

This medicine must not be given to a child under the age of 2 years unless directed by the child's doctor. Safety and effectiveness in children younger than 2 years have not been established.

If you are not sure whether you should be receiving this medicine, talk to your doctor.

Before you start to receive TAZOPIP

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any other health problems, including kidney or liver disease. The dose of TAZOPIP will be altered, depending on the blood tests.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor can discuss with you the risks and benefits involved if you are pregnant.

Tell your doctor if you are breastfeeding. TAZOPIP passes into breastmilk. Therefore, if you are breastfeeding, you should discuss with your doctor whether to stop breastfeeding while or stop using TAZOPIP.

Tell your doctor if you are on a low salt diet.

Tell your doctor if you are being treated with TAZOPIP for gonorrhoea, your doctor should test you for syphilis as well. TAZOPIP in high doses may hide early symptoms of syphilis without curing it long-term.

If you have not told your doctor about any of the above, tell them before you start taking TAZOPIP.

If you are not sure whether you should be taking TAZOPIP, talk to your doctor.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and TAZOPIP may interfere with each other. These include:

  • medicines used to treat gout such as probenecid
  • aminoglycoside antibiotics including tobramycin
  • vancomycin, an antibiotic
  • preparations used for thinning blood (warfarin, heparin)
  • methotrexate, used to treat cancer, rheumatoid arthritis and other inflammatory conditions
  • vecuronium, a muscle relaxant used in surgery.

These medicines may be affected by TAZOPIP or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

If you have not told your doctor about any of the above, tell them before you start taking TAZOPIP.

How TAZOPIP will be given to you

How much you will be given

The usual dosage for adults and children is 4 g piperacillin/0.5 g tazobactam (TAZOPIP) given every eight hours. The dose can vary from 2g piperacillin/0.25g tazobactam to 4g piperacillin /0.5g tazobactam administered every six or eight hours.

For children aged 2 to 12 years weighing up to 40 kg and with normal kidney function, the recommended dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram every 8 hours.

For children aged 2 to 12 years weighing over 40 kg and with normal kidney function, follow the adult dose guidance, i.e. 4g piperacillin/0.5g tazobactam every 8 hours.

Your doctor may change these dosages.

If you have kidney disease your doctor will adjust the dose to suit you.

How TAZOPIP will be given to you

A doctor or nurse in hospital will always give TAZOPIP to you. It will usually be given to you as a slow injection into a vein over 20-30 minutes.

How long TAZOPIP will be given to you

The length of time you will be given TAZOPIP depends on the type and severity of your infection. It should be given for at least five days, and for 48 hours after all signs of illness and fever have gone.

If you take too much (overdose)

It is unlikely that you will ever receive an overdose of TAZOPIP because it will be given by a trained nurse or doctor.

Symptoms of an overdose are the same as side effects but may be more severe. The symptoms of a side effect are listed under Side Effects below.

Immediately contact your doctor or go to Accident and Emergency department at the nearest hospital, if you notice the symptoms of an overdose. Contact the Poisons Information Centre on 13 11 26 for further advice on overdose management.

While you are receiving TAZOPIP

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may wish to do some blood tests if you receive TAZOPIP for a prolonged time to make sure the medicine is working and to prevent unwanted side effects. Sometimes blood disorders can occur if you take TAZOPIP.

If you are asked by a doctor for a urine sample, tell him/her that you are receiving TAZOPIP. Antibiotics in the penicillin family, including TAZOPIP, can cause interference in some tests for glucose in urine. Penicillins that are excreted in urine can cause a false-positive result. The doctor will request a test, which is not affected by penicillins.

Things you must do

If you develop severe diarrhoea, tell your doctor immediately. Do this even if it occurs several weeks after stopping TAZOPIP. This may be a sign of a serious side effect that affects the bowel. You may need urgent medical care.

Do not take any medicines to treat the diarrhoea without first checking with your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking TAZOPIP.

This medicine is effective in most people but it may have unwanted side effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Tell your doctor or pharmacist if you notice any of the following and they worry you.

More common side effects are:

  • nausea or indigestion
  • vomiting
  • diarrhoea or constipation
  • rash, itchy or red skin
  • allergic reactions such as hives
  • a new infection. May be caused by bacteria that are resistant to TAZOPIP (superinfection)
  • difficulty sleeping
  • headache, dizziness or light-headedness

Rare side effects are:

  • increased sweating
  • eczema
  • flaking or peeling of the skin
  • inflammation of the mouth
  • dry mouth
  • weakness and tiredness
  • hallucinations or severe confusion
  • muscle or joint pain or prolonged muscle relaxation
  • fever
  • hot flushes
  • swelling of the hands, feet and ankles
  • swelling or redness along a vein which is extremely tender when touched
  • changes in liver function including jaundice (yellowing of skin and eyes) or hepatitis
  • severe diarrhoea caused by a certain superinfection in the gut
  • convulsions ('fits') if TAZOPIP is given in high doses
  • short-term changes in kidney function
  • cough, fever, chills, shortness of breath and chest pain
  • thrush, especially with prolonged treatment.

The above list includes serious side effects that may require medical attention. Serious side effects occur less often in people taking TAZOPIP.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • pain, swelling, or redness around the injection site
  • skin rash
  • itchiness.

Tell your doctor as soon as possible if you notice any of the following:

  • severe blisters and bleeding in the lips, eyes, mouth, nose or genitals
  • itchy spots accompanied by fever and feeling unwell
  • tiredness, being short of breath and looking pale
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal, nose bleeds

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

This is not a complete list of side effects. Other side effects not listed above may also occur in some people; there may be some side effects not yet know.

Tell your doctor if you notice anything on this list or anything else that is making you feel unwell.

Importantly, tell your doctor if you have severe diarrhoea in the next few weeks after TAZOPIP treatment.

Do not try to treat yourself with medicines that you can purchase without a prescription.

Do not be alarmed by the list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

After using TAZOPIP

Storage

TAZOPIP will be stored in the surgery, pharmacy or ward of a hospital. The injection is kept in a cool dry place protected from light where the temperature stays below 25 °C.

It is unlikely that you will be asked to store this medicine. However, if you are:

Keep this medicine where young children cannot reach it. A locked cupboard at least 1 and a half metres above the ground is a good place to store medicines.

Keep it in a cool dry place where it stays below 25°C. Protect from light. Do not store it in a bathroom or near a sink.

Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking TAZOPIP, or it has passed its expiry date, ask your pharmacist what to do with any left over.

Product description

What it looks like

TAZOPIP is a white to off-white powder packaged in glass containers (vials).

Ingredients

TAZOPIP contains 4g/0.5g of tazobactam as the active ingredients mixed with sterile liquid to give a solution for injection by your doctor.

This medicine does not contain any excipients or preservatives.

Supplier

TAZOPIP is supplied in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in March 2022.

Australian registration number:

AUST R 144970 - TAZOPIP 4g/0.5g
piperacillin and tazobactam powder for injection

TAZOPIP_cmi\Mar22/00

Published by MIMS April 2022

BRAND INFORMATION

Brand name

Tazopip

Active ingredient

Piperacillin; Tazobactam

Schedule

S4

 

1 Name of Medicine

Piperacillin (as sodium) and tazobactam (as sodium).

2 Qualitative and Quantitative Composition

Tazopip is an injectable antibacterial combination, consisting of the semisynthetic antibiotic piperacillin sodium and the beta-lactamase inhibitor tazobactam sodium, for intravenous administration.
Each vial of Tazopip contains piperacillin and tazobactam 2 g/0.25 g or 4 g/0.5 g (as the sodium salts). The product contains no excipients or preservatives.

3 Pharmaceutical Form

Powder for injection.
Tazopip is available as a white to off-white sterile, cryodesiccated powder of piperacillin and tazobactam as the sodium salts packaged in glass vials.

4 Clinical Particulars

4.1 Therapeutic Indications

Tazopip for injection is indicated in the treatment of serious bacterial infections caused by susceptible strains of beta-lactamase producing organisms in the conditions listed below.
Lower respiratory tract infections.
Urinary tract infections (complicated and uncomplicated).
Intra-abdominal infections.
Skin and skin structure infections.
Bacterial septicaemia.
Gynaecological infections.

Children under the age of 12 years.

In hospitalised children aged 2 to 12 years, Tazopip for injection is indicated for the treatment of serious intra-abdominal infections. It has not been evaluated in this indication for paediatric patients below the age of 2 years.
While Tazopip for injection is indicated only for the conditions listed above, it may be used as a single agent in the treatment of mixed infections caused by piperacillin susceptible and beta-lactamase producing, piperacillin resistant organisms. Appropriate culture and susceptibility tests should be performed before treatment in order to identify organisms causing infection to determine their susceptibilities to Tazopip. Therapy with Tazopip for injection may be initiated before results of such tests are known when there is reason to believe the infection may involve any of the beta-lactamase producing organisms listed above; however, once these results become available, appropriate therapy should be continued.
In serious infections, presumptive therapy with Tazopip for injection may be initiated before susceptibility test results are available.

Note.

For associated bacteraemia due to extended-beta-lactamase (ESBL) producing organisms, see Section 5.1 Pharmacodynamic Properties.
Combination therapy with Tazopip for injection and aminoglycosides may be used in the treatment of serious infections caused by Pseudomonas aeruginosa. Both drugs should be used in full therapeutic doses. As soon as results of culture and susceptibility tests become available, antimicrobial therapy should be adjusted.

4.2 Dose and Method of Administration

Dosage.

Tazopip for injection may be given by slow intravenous infusion (20-30 minutes).
Adults and children 12 years and older. The usual intravenous dosage for adults and children with normal renal function is 4 g piperacillin/0.5 g tazobactam (Tazopip) given every eight hours.
The total daily dose depends on the severity and localisation of the infection and can vary from 2 g piperacillin/0.25 g tazobactam to 4 g piperacillin/0.5 g tazobactam (Tazopip) administered every six or eight hours.
Children aged 2 to 12 years.

Hospitalised children with intra-abdominal infection.

For children aged 2 to 12 years weighing up to 40 kg and with normal renal function, the recommended dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram every 8 hours.
For children aged 2 to 12 years weighing over 40 kg and with normal renal function, follow the adult dose guidance, i.e. 4 g piperacillin/0.5 g tazobactam every 8 hours.
The duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress. Therapy is recommended to be a minimum of 5 days and a maximum of 14 days, considering that dose administration should continue at least 48 hours after the resolution of clinical signs and symptoms.

Dosage adjustment in renal insufficiency.

In patients with renal insufficiency, the intravenous dose should be adjusted to the degree of actual renal function impairment. The suggested daily doses are shown in Table 1.
For patients on haemodialysis, the maximum daily dose is 8 g/1 g per day Tazopip for injection. In addition, because haemodialysis removes 30-50% of piperacillin in 4 hours, one additional dose of 2 g piperacillin/0.25 g tazobactam should be administered following each dialysis period. For patients with renal failure and hepatic insufficiency, measurement of serum levels of piperacillin/tazobactam will provide additional guidance for adjusting dosage.

Children aged 2 to 12 years.

The pharmacokinetics of piperacillin/ tazobactam have not been studied in paediatric patients with renal impairment. Each patient must be monitored closely for signs of drug toxicity. Drug dose and interval should be adjusted accordingly.

Duration of therapy.

In acute infections, treatment with Tazopip for injection should be for a minimum of five days and continued for 48 hours beyond resolution of clinical symptoms or the fever.

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.
In circumstances where co-administration is preferred, Tazopip for injection is compatible for simultaneous co-administration via Y-site infusion only with the following aminoglycosides under the following conditions.
Compatibility of Tazopip for injection with other aminoglycosides has not been established. Only the concentration and diluents for amikacin and gentamicin with the dosages of Tazopip listed in Table 2 have been established as compatible for coadministration via Y-site infusion. Simultaneous co-administration via Y-site in any manner other than listed above may result in inactivation of the aminoglycoside by piperacillin/ tazobactam.

Administration.

Reconstitution directions.

Use sterile water for injections or sodium chloride injection as diluents for reconstitution.
 Product is for single use in one patient only. Discard any residue.
A needle with 21G [0.8 mm] diameter size is advised to be used for reconstitution. When inserting syringe into the vial, via the rubber stopper, it is recommended to slice the bung with the beveled edge facing upwards (see Section 4.4 Special Warnings and Precautions for Use).

For intravenous use.

Reconstitute each vial with the volume of diluent shown in Table 3, using one of the above diluents. Shake until dissolved.
The reconstituted solution may be further diluted to 50 mL with saline, 5% glucose or dextran 6% in saline.
To reduce microbiological hazard, use as soon as possible after preparation. If storage is necessary, hold at 2°C to 8°C for not more than 24 hours.

4.3 Contraindications

The use of Tazopip for injection is contraindicated in patients with a history of allergic reaction to any of the penicillins and/or cephalosporins or beta-lactamase inhibitors.

4.4 Special Warnings and Precautions for Use

Because of its poor penetration into the CSF, piperacillin is not advised in the treatment of meningitis and brain abscess.
Antimicrobials used in high doses for short periods to treat gonorrhoea may mask or delay symptoms of incubating syphilis. Therefore, prior to treatment, patients with gonorrhoea should also be evaluated for syphilis. Specimens for darkfield examination should be obtained from patients with any suspected primary lesion and serological tests should be made for a minimum of 4 months.
The theoretical sodium content of each vial of Tazopip for injection is 54 mg sodium (2.35 mEq) per gram of piperacillin, which may increase a patient's overall sodium intake. Periodical electrolyte determinations should be made in patients with low potassium reserves and the possibility of hypokalaemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics. As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously.
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.
Repeated use of lidocaine (lignocaine) as diluent should be avoided in patients with severe liver disease or decreased hepatic blood flow due to the possibility of lidocaine (lignocaine) toxicity (resulting from decreased metabolism and accumulation).
Combined use of piperacillin/ tazobactam and vancomycin may be associated with an increased risk of acute kidney injury.
It is advised to use a needle with 21G [0.8 mm] diameter size, for reconstitution. When inserting syringe into the vial, via the rubber stopper, it is recommended to slice the bung with the beveled edge facing upwards (see Section 4.2 Dose and Method of Administration).

Hypersensitivity reactions.

Serious and occasionally fatal hypersensitivity (anaphylactic/ anaphylactoid, including shock) reactions have been reported in patients on penicillin/ cephalosporin therapy including piperacillin/ tazobactam. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins/ cephalosporins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin/ cephalosporin hypersensitivity who have experienced severe reactions when treated with either a penicillin or cephalosporin. Past history of a severe allergic reaction to penicillin/ cephalosporin is a contraindication to the use of Tazopip for injection. Before initiating therapy with any penicillin/ cephalosporin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, Tazopip for injection should be discontinued and the appropriate therapy instituted. Serious anaphylactic/ anaphylactoid reactions (including shock) require immediate emergency treatment with adrenaline (epinephrine). Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.
Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, Tazopip should be discontinued immediately and an alternative treatment should be considered.
Rare cases of haemophagocytic lymphohistiocytosis (HLH) have been observed following therapy (>10 days) with piperacillin tazobactam, often as a complication of DRESS. HLH is a pathologic immune activation which leads to excessive systemic inflammation and can be life threatening and early diagnosis and rapid initiation of immunosuppressive therapy is essential. Characteristic signs and symptoms include fever, hepatosplenomegaly, cytopenias, hyperferritinaemia, hypertriglyceridaemia, hypofibrinogenaemia, and haemophagocytosis. If piperacillin tazobactam is suspected as possible trigger, treatment should be discontinued.

Pseudomembranous colitis.

Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including piperacillin. A toxin produced by Clostridioides difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against C. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs that delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.

Bleeding manifestations.

Bleeding manifestations have occurred in some patients receiving piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time and are more likely to occur in patients with renal failure. If bleeding manifestations occur, the antibiotic should be discontinued and appropriate therapy instituted.

Hepatic effects.

Combined administration of beta-lactamase inhibitors and beta-lactam antibiotics may be associated with a slightly increased risk of hepatic adverse reactions. The incidence of increased liver enzymes in patients treated with Tazopip for injection was slightly higher than has been reported previously with the use of piperacillin alone. The potential for increased hepatic adverse reactions should be borne in mind when using Tazopip for injection.

Prolonged therapy.

The possibility of the emergence of resistant organisms that might cause superinfections should be kept in mind, particularly during prolonged treatment. If this occurs, appropriate measures should be taken.
Leucopenia and neutropenia may occur, especially during prolonged therapy. Therefore, periodic assessment of haematopoietic function should be performed.
Periodical assessment of organ system functions including renal, hepatic and haematopoietic during prolonged therapy (21 days or more) is advisable.

Use in renal impairment.

Due to its potential nephrotoxicity (see Section 4.8 Adverse Effects (Undesirable Effects)), piperacillin/tazobactam should be used with care in patients with renal impairment or dialysis patients (haemodialysis and CAPD). In patients with renal insufficiency and dialysis patients, the intravenous dose and administration interval should be adjusted to the degree of renal function impairment (see Section 4.2 Dose and Method of Administration). Measurement of serum levels of piperacillin will provide guidance for adjusting dosage (see Section 4.2 Dose and Method of Administration).
As with treatment with other penicillins, neurological complications in the form of convulsions (seizures) may occur when high doses are administered, especially in patients with impaired renal function (see Section 4.8 Adverse Effects (Undesirable Effects)).
In a secondary analysis using data from a large multicenter, randomised controlled trial when glomerular filtration rate (GFR) was examined after administration of frequently used antibiotics in critically ill patients, the use of piperacillin/ tazobactam was associated with a lower rate of reversible GFR improvement compared with the other antibiotics. This secondary analysis concluded that piperacillin/ tazobactam was a cause of delayed renal recovery in these patients.
Combined use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in the elderly.

No data available.

Paediatric use.

Safety and efficacy of the use of Tazopip for injection in children under the age of 2 years has not yet been established.

Effects on laboratory tests.

As with other penicillins, the administration of piperacillin/tazobactam may result in a false-positive reaction for glucose in the urine using a copper-reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
There have been reports of positive test results using Bio-Rad Laboratories Platelia Aspergillus enzyme immunoassay (EIA) test in patients receiving Tazopip for injection, who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving Tazopip for injection should be interpreted cautiously and confirmed by other diagnostic methods.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Probenecid.

Concurrent administration of probenecid and Tazopip for injection produces a longer half-life and lower renal clearance for both piperacillin and tazobactam. However, peak plasma concentrations of neither drug are affected.

Vancomycin.

Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/ tazobactam and vancomycin as compared to vancomycin alone (see Section 4.4 Special Warnings and Precautions for Use). Some of these studies have reported that the interaction is vancomycin dose-dependent. Expert guidelines recommend intensive vancomycin dosing and maintenance of trough levels between 15 mg/L and 20 mg/L which is an increase from previously published recommendations of target trough concentrations of 5-10 mg/L. Attaining these trough concentrations often requires practitioners to prescribe vancomycin doses which exceed manufacturers' recommendations. Therefore, it is possible that in addition to the increased risk of vancomycin-induced nephrotoxicity reported with adherence to these guidelines the risk of nephrotoxicity may also increase due to an interaction with piperacillin/ tazobactam.

Aminoglycosides.

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 in vitro with Tazopip for injection in certain diluents at specific concentrations for a simultaneous Y-site infusion (see Section 4.2 Dose and Method of Administration).
The inactivation of aminoglycosides in the presence of penicillin class drugs has been recognised. It has been postulated that penicillin aminoglycoside complexes form; these complexes are microbiologically inactive and of unknown toxicity.
Concurrent administration of piperacillin and tobramycin in patients with severe renal dysfunction (i.e. chronic haemodialysis patients) has been reported to reduce the elimination half-life and significantly increase the total body clearance of tobramycin.
The alteration of tobramycin pharmacokinetics in patients with mild to moderate renal dysfunction who are taking piperacillin concomitantly is unknown. However, reports suggest that the aminoglycoside inactivation in patients concomitantly taking an aminoglycoside with a broad spectrum beta-lactam penicillin is only clinically significant in patients with severe renal dysfunction.

Other antibiotics.

If Tazopip for injection is used concurrently with another antibiotic, especially an aminoglycoside, the drugs must not be mixed in intravenous solutions or administered concurrently due to physical incompatibility.

Non-depolarising muscle relaxants.

Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Tazopip for injection (piperacillin/ tazobactam) could produce the same phenomenon if given along with vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the nondepolarising muscle relaxants could be prolonged in the presence of piperacillin.

Methotrexate.

Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.

Heparin and anticoagulants.

During simultaneous administration of high doses of heparin, oral anticoagulants and other medicines that may affect the blood coagulation system and/or the thrombocyte function, the coagulation parameters should be tested more frequently and monitored regularly.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Piperacillin and tazobactam did not affect the fertility of male or female rats.
(Category B1)
Adequate human studies on the use of Tazopip for injection during pregnancy are not available. Limited studies with piperacillin alone in rats and mice revealed no teratogenic effects or harm to the foetus. Studies with tazobactam (doses up to 3000 mg/kg IV) or tazobactam and piperacillin (doses up to 750 mg/kg and 3000 mg/kg IV) in mice showed no evidence of teratogenicity or harm to the foetus. Studies in rats at these dose levels showed no evidence of teratogenicity though maternal toxicity in the form of decreased weight gain, was noted at the dose levels tested. Piperacillin and tazobactam has been found to cross the placenta in humans. Pregnant women should be treated only if the expected benefit outweighs the possible risks to the pregnant woman and foetus.
Australian categorisation definition of Category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
Adequate clinical studies on the use of Tazopip for injection during lactation are not available. Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. In animal studies, both piperacillin and tazobactam were excreted in the milk of lactating rats. Women who are breastfeeding should be treated only if the expected benefit outweighs the possible risks to the woman and child.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Tazopip for injection is generally well tolerated. The overall incidence of adverse events was 15.7% although a cause/ effect relationship was not established in all cases. This incidence was comparable to that observed with other agents used in the clinical studies. Treatment had to be discontinued in only 2.9% of cases due to adverse reactions.
The most frequently reported adverse clinical reactions were diarrhoea, rash, erythema, pruritus, vomiting, allergic reactions, nausea, urticaria, superinfection, phlebitis, thrombophlebitis, dyspepsia and insomnia.

Clinical experience.

The following adverse reactions have been reported in clinical trials and are listed in Council for International Organisations of Medical Sciences (CIOMS) frequency categories as follows: very common: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare: ≥ 0.01% and < 0.1%; very rare: < 0.01%; unknown: cannot be estimated from available data.

Blood and lymphatic system.

Uncommon: leucopenia, neutropenia, thrombocytopenia. Rare: anaemia, eosinophilia. Very rare: disturbed thrombocyte function.

Gastrointestinal.

Common: diarrhoea (including soft/ loose stools), nausea, vomiting. Uncommon: constipation, dyspepsia, stomatitis. Rare: abdominal pain.

General disorders and administration site conditions.

Uncommon: fever, injection site reaction (pain, inflammation). Rare: rigors, chills. Unknown: hot flushes, oedema, tiredness.

Infections and infestations.

Rare: pseudomembranous colitis.

Investigations.

Uncommon: alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood creatinine increased. Rare: bleeding manifestations (including bleeding time prolonged), blood bilirubin increased*, blood alkaline phosphatase increased*, gamma glutamyltransferase increased*. Very rare: Coombs' direct test positive, prolonged partial thromboplastin time, prothrombin time prolonged, blood albumin decreased, blood glucose decreased, blood total protein decreased, blood urea nitrogen increased.
*The incidence of such rises is higher than with piperacillin alone.

Metabolism and nutrition disorders.

Very rare: hypokalaemia.
Hypokalaemia was reported in patients with liver disease and those receiving cytotoxic therapy or diuretics when given high doses of piperacillin.

Musculoskeletal, connective tissue and bone disorders.

Rare: arthralgia. Unknown: muscular weakness, muscle pain, prolonged muscle relaxation.

Nervous system disorders.

Uncommon: headache. Unknown: hallucination, dizziness, dry mouth.

Psychiatric disorders.

Uncommon: insomnia.

Skin and subcutaneous tissue disorders.

Common: rash. Uncommon: pruritus, urticaria. Rare: eruption (including bullous dermatitis), purpura. Unknown: increased sweating, eczema, exanthema.

Renal and urinary disorders.

Rare: tubulointerstitial nephritis, renal failure.

Respiratory, thoracic and mediastinal disorders.

Rare: epistaxis.

Vascular disorders.

Uncommon: phlebitis, hypotension, thrombophlebitis. Rare: flushing. Unknown: tachycardia, including supraventricular and ventricular, bradycardia, arrhythmia, including atrial fibrillation, ventricular fibrillation, cardiac arrest, cardiac failure, circulatory failure, myocardial infarction.

Postmarketing experience.

Additional adverse events reported from worldwide marketing experience with Tazopip for injection, occurring under circumstances where causal relationship with Tazopip is uncertain.

Blood and lymphatic system.

Rare: haemolytic anaemia. Very rare: agranulocytosis, pancytopenia, thrombocytosis.

Hepatobiliary.

Uncommon: jaundice. Rare: hepatitis.
Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

Immune system disorders.

Uncommon: hypersensitivity reaction. Rare: anaphylactic/ anaphylactoid reaction (including shock).

Infections and infestations.

Uncommon: candidal superinfection (especially with prolonged treatment).

Psychiatric disorders.

Unknown: delirium.

Nervous system disorders.

Uncommon: Seizure.

Respiratory, thoracic and mediastinal disorders.

Unknown: eosinophilic pneumonia.

Renal and urinary disorders.

Rare: interstitial nephritis, renal failure. Unknown: acute renal injury.

Skin and subcutaneous tissue disorders.

Uncommon: rash maculopapular. Rare: erythema multiforme. Very rare: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN). Unknown: drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), dermatitis exfoliative.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There have been postmarketing reports of overdose with piperacillin/ tazobactam. The majority of symptoms experienced, including nausea, vomiting and diarrhoea, have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).
No specific antidote is known. Treatment should be supportive and symptomatic according to the patient's clinical presentation. In the event of an emergency, all required intensive medical measures are indicated as in the case of piperacillin. In cases of motor excitability or convulsions, anticonvulsive agents (e.g. diazepam or barbiturates) may be indicated. In cases of anaphylactic reactions, the usual counter measures are to be initiated (adrenaline (epinephrine), antihistamines, corticosteroids and, if required, oxygen and airway management). Excessive serum concentrations of either piperacillin or tazobactam may be reduced by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Piperacillin, a broad spectrum, semisynthetic penicillin active against many Gram positive and Gram negative aerobic and anaerobic bacteria, exerts bactericidal activity by inhibition of both septum and cell wall synthesis. Tazobactam, a triazolylmethyl penicillanic acid sulfone, is a potent inhibitor of many beta-lactamases, including the plasmid and chromosomally mediated enzymes that commonly cause resistance to penicillins. The presence of tazobactam in the Tazopip formulation enhances and extends the antibiotic spectrum of piperacillin to include many beta-lactamase producing bacteria normally resistant to it. Thus, Tazopip combines the properties of a broad spectrum antibiotic and a beta-lactamase inhibitor.
Piperacillin and other β-lactam antibiotics block the terminal transpeptidation step of cell wall peptidoglycan biosynthesis in susceptible bacteria by interacting with penicillin-binding proteins (PBPs), the bacterial enzymes that carry out this reaction. In vitro, piperacillin is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria.
Piperacillin has reduced activity against bacteria harbouring certain β-lactamase enzymes, which chemically inactivate piperacillin and other β-lactam antibiotics. Tazobactam sodium, which has very little intrinsic antimicrobial activity, due to its low affinity for PBPs, can restore or enhance the activity of piperacillin against many of these resistant organisms. Tazobactam is a potent inhibitor of many class A β-lactamases (penicillinases, cephalosporinases and extended spectrum enzymes). It has variable activity against class A carbapenemases and class D β-lactamases. It is not active against most class C cephalosporinases and inactive against Class B metallo-β-lactamases.
Two features of piperacillin/tazobactam lead to increased activity against some organisms harbouring β-lactamases that, when tested as enzyme preparations, are less inhibited by tazobactam and other inhibitors: tazobactam does not induce chromosomally mediated β-lactamases at tazobactam levels achieved with the recommended dosing regimen and piperacillin is relatively refractory to the action of some β-lactamases.
Like other β-lactam antibiotics, piperacillin, with or without tazobactam, demonstrates time-dependent bactericidal activity against susceptible organisms.

Mechanism of resistance.

There are three major mechanisms of resistance to β-lactam antibiotics: changes in the target penicillin-binding proteins (PBPs) resulting in reduced affinity for the antibiotics, destruction of the antibiotics by bacterial β-lactamases, and low intracellular antibiotic levels due to reduced uptake or active efflux of the antibiotics.
In gram-positive bacteria, changes in PBPs are a major mechanism of resistance to β-lactam antibiotics, including piperacillin/tazobactam. This mechanism is responsible for methicillin resistance in staphylococci and penicillin resistance in Streptococcus pneumoniae as well as viridans group streptococci and enterococci. Resistance caused by changes in PBPs also occurs to a lesser extent in fastidious gram-negative species such as Haemophilus influenzae and Neisseria gonorrhoeae. Piperacillin/tazobactam is not active against strains in which resistance to β-lactam antibiotics is determined by altered PBPs. As indicated above, there are some β-lactamases that are not inhibited by tazobactam.

Antibacterial spectrum (groupings of relevant species according to piperacillin/tazobactam susceptibility).

Commonly susceptible species.

Aerobic gram-negative bacteria.

Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Proteus mirabilis.

Aerobic gram-positive bacteria.

Enterococcus faecalis (ampicillin-or penicillin-susceptible isolates only), Listeria monocytogenes, Staphylococcus aureus (methicillin-susceptible isolates only), Staphylococcus spp., coagulase-negative (methicillin-susceptible isolates only), Streptococcus agalactiae (Group B streptococci)+, Streptococcus pyogenes (Group A streptococci)+.

Anaerobic gram-positive bacteria.

Clostridium spp., Eubacterium spp., Anaerobic gram-positive cocci++.

Anaerobic gram-negative bacteria.

Bacteroides fragilis group, Fusobacterium spp., Porphyromonas spp., Prevotella spp..
Species for which acquired resistance may be a problem.

Aerobic gram-positive bacteria.

Enterococcus faecium, Streptococcus pneumoniae++, Viridans group streptococci++.

Aerobic gram-negative bacteria.

Acinetobacter baumannii, Citrobacter freundii, Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Serratia spp..

Anaerobic gram-positive bacteria.

Clostridium perfringens.

Anaerobic gram-negative bacteria.

Bacteroides distasonis, Prevotella melaninogenica.
Inherently resistant organisms.

Aerobic gram-positive bacteria.

Corynebacterium jeikeium.

Aerobic gram-negative bacteria.

Burkholderia cepacia, Legionella spp., Stenotrophomonas maltophilia.

Others.

Chlamydophila pneumoniae, Mycoplasma pneumoniae.
+ Streptococci are not β-lactamase producing bacteria; resistance in these organisms is due to alterations in PBPs and, therefore, piperacillin/tazobactam-susceptible isolates are susceptible to piperacillin alone. Penicillin resistance has not been reported in S. pyogenes.
++ Including Anaerococcus, Finegoldia, Peptococcus, Peptoniphilus, and Peptostreptococcus spp. (CLSI M100 Ed. 29, 2019).
Disc susceptibility test. Susceptibility testing should be conducted using standardised laboratory methods such as those described by the Clinical and Laboratory Standards Institute (CLSI). These include dilution methods (minimal inhibitory concentration [MIC] determination) and disk susceptibility methods. Standardised susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the laboratory procedures. Quality control microorganisms are specific strains with intrinsic biological properties relating to resistance mechanisms and their genetic expression within the microorganism; the specific strains used for susceptibility test quality control are not clinically significant.
A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "intermediate" indicates that the result should be considered equivocal and, if the microorganism is not fully susceptible to alternative, clinically feasible medicines, the test should be repeated. This category implies possible clinical applicability in body sites where the medicine is physiologically concentrated or in situations where high dosage of the medicine can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information of resistance is desirable, particularly when treating severe infections. This information provides guidance on microorganisms susceptible to piperacillin/ tazobactam. The following MIC90 values were reported in 1996 for clinical isolates collected in 3 Australian states (see Table 4).
The CLSI interpretive criteria for susceptibility testing of piperacillin/tazobactam are listed in Table 5.
Organisms and quality control ranges for piperacillin/tazobactam to be utilised with CLSI methodology and susceptibility test interpretive criteria are listed in Table 6.

Clinical trials.

MERINO trial (blood stream infections due to ESBL producing organisms).

In a prospective, randomised non-inferiority clinical trial, definitive (i.e. based on susceptibility confirmed in-vitro) treatment with piperacillin/tazobactam did not meet non-inferiority versus meropenem in regard to 30-day mortality in the treatment of blood stream infections due to ESBL producing E. coli or Klebsiella pneumoniae in critically ill adult patients. A total of 23 of 187 patients (12.3%) randomised to piperacillin/tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomised to meropenem (risk difference, 8.6% [1-sided 97.5% CI: -∞ to 14.5%]; P = 0.90 for non-inferiority). Clinical and microbiological resolution by day 4 occurred in 121 of 177 patients (68.4%) in the piperacillin/tazobactam group compared with 138 of 185 (74.6%), randomised to meropenem (risk difference, -6.2% [95% CI: -15.5 to 3.1%]; P = 0.19). The cause of the mortality imbalance is not clear.

Paediatric.

A study was performed to compare the safety, tolerance and efficacy of 100 mg/kg piperacillin plus 12.5 mg/kg tazobactam with those of 50 mg/kg cefotaxime plus 7.5 mg/kg metronidazole administered intravenously (IV) every 8 hours for the treatment of hospitalised paediatric patients (aged 2 to 12 years of age) with clinically or bacteriologically diagnosed intra-abdominal infection (IAI). The cure rates in the efficacy evaluable (EE) population at the follow-up visit were 90% and 91% for piperacillin/ tazobactam and cefotaxime/ metronidazole, respectively. The results of the clinical and microbiological analyses in 521 patients showed that piperacillin/ tazobactam administered intravenously was at least as effective as cefotaxime/ metronidazole in the treatment of children aged 2 to 12 years with severe IAIs.

5.2 Pharmacokinetic Properties

Distribution.

Mean plasma concentrations of piperacillin and tazobactam at steady state of the combination appear in Tables 7 and 8. Peak piperacillin and tazobactam plasma concentrations are attained immediately after completion of an intravenous infusion. When given with tazobactam, piperacillin plasma levels are similar to those attained when equivalent doses of piperacillin are administered alone.
In healthy subjects piperacillin/ tazobactam plasma elimination half-lives range from 0.7 to 1.2 hours following single or multiple doses. These half-lives are unaffected by dose or duration of infusion. Piperacillin and tazobactam are 21% and 23%, respectively, bound to plasma proteins. The protein binding of either piperacillin or tazobactam is unaffected by the presence of either compound. Piperacillin and tazobactam are widely distributed in tissues and body fluids including intestinal mucosa, gall bladder, lung and bile.

Metabolism.

Piperacillin does not undergo biotransformation in humans. Approximately 20% of a dose of tazobactam is metabolised to a single metabolite that has been found to be microbiologically inactive.

Excretion.

Piperacillin and tazobactam are eliminated by the kidney via glomerular filtration and tubular secretion. Piperacillin is excreted rapidly as unchanged drug, with 69% of the dose appearing in the urine. Piperacillin is also secreted into bile. Tazobactam and its metabolite are eliminated primarily by renal excretion, with 80% of the dose appearing as unchanged drug and the remainder of the dose appearing as the metabolite.

Impaired renal function.

The half-life of piperacillin and tazobactam increases with decreasing creatinine clearance. The increase is twofold and fourfold for piperacillin and tazobactam respectively at creatinine clearance below 20 mL/min compared to patients with normal renal function. Dosage adjustments are recommended when creatinine clearance is below 40 mL/min (see Section 4.2 Dose and Method of Administration).
Piperacillin and tazobactam are removed from the body during haemodialysis with 31% and 39% of the doses of piperacillin and tazobactam, respectively, recovered in the dialysis fluid. Piperacillin and tazobactam are removed from the body by peritoneal dialysis with 5% and 12% of the dose respectively appearing in the dialysate. For dosage recommendations in patients undergoing haemodialysis, see Section 4.2 Dose and Method of Administration.

Impaired liver function.

Piperacillin half-life and AUC were increased by 25% and 40% respectively and tazobactam half-life and AUC by 18% and 23% respectively in patients with hepatic impairment. However, dosage adjustments in patients with hepatic impairment are not necessary.

Children.

The pharmacokinetics of piperacillin and tazobactam have been examined in 24 paediatric patients aged 2 months to 12 years receiving 100 mg/kg piperacillin plus 12.5 mg/kg tazobactam (Table 9). The maximum concentration (Cmax) for both piperacillin and tazobactam is increased relative to the maximum adult dose but the predicted time above the minimum inhibitory concentration is slightly decreased. The dosage of 100 mg/kg piperacillin plus 12.5 mg/kg tazobactam administered every 8 hours is predicted to provide coverage 31-61% of the time for the range of MIC values of 2-16 microgram/mL commonly found in intra-abdominal infections in children.

5.3 Preclinical Safety Data

Genotoxicity.

Mutagenicity studies with piperacillin and tazobactam showed no evidence of genotoxicity in assays for chromosomal and DNA damage. One assay for gene mutations (Mouse lymphoma assay) was weakly positive at tazobactam and piperacillin concentrations greater than or equal to 3200 microgram/mL and 2500 microgram/mL, respectively.

Carcinogenicity.

Long term carcinogenicity studies of Tazopip for injection in animals have not been performed.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each vial contains a total of 2.35 mEq (54 mg) of sodium per gram of piperacillin. The product contains no excipients or preservatives.

6.2 Incompatibilities

Tazopip for injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established. Whenever Tazopip for injection is used concurrently with another antibiotic, the drugs must be administered separately. Due to the in vitro inactivation of aminoglycosides by beta-lactam antibiotics, Tazopip for injection and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated.
Because of chemical instability, Tazopip for injection should not be used with lactated Ringer's solution, solutions containing only sodium bicarbonate or having a pH in the basic range.
Tazopip for injection should not be added to blood products or albumin hydrolysates.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Tazopip 2 g/0.25 g powder for injection.

Store below 25°C. Protect from light.

Tazopip 4 g/0.5 g powder for injection.

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Tazopip 2 g/0.25 g powder for injection: 2.25 g vial containing piperacillin sodium 2.085 g equivalent to 2 g piperacillin and tazobactam sodium 0.2683 g equivalent to 0.25 g tazobactam.
Packs of 1, glass type I clear vial.
Tazopip 4 g/0.5 g powder for injection: 4.5 g vial containing piperacillin sodium 4.170 g equivalent to 4 g piperacillin and tazobactam sodium 0.5366 g equivalent to 0.5 g tazobactam.
Packs of 1 and 10, glass type I clear vial.
Not all pack sizes may be marketed.

Australian Register of Therapeutic Goods (ARTG).

AUST R 144969 - Tazopip 2 g/0.25 g piperacillin (as sodium) 2 g and tazobactam (as sodium) 0.25 g powder for injection vial.
AUST R 144970 - Tazopip 4 g/0.5 g piperacillin (as sodium) 4 g and tazobactam (as sodium) 0.5 g powder for injection vial.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Piperacillin (as sodium).

Chemical name: sodium (2S,5R,6R)- 6-[[(2R)-2-[[(4-ethyl-2,3- dioxopiperazin-1-yl) carbonyl]amino]-2-phenylacetyl]amino]- 3,3-dimethyl-7-oxo- 4-thia-1-azabicyclo [3.2.0]heptane-2- carboxylic acid.
Structural formula:
Molecular formula: C23H26N5NaO7S.
Molecular weight: 539.54.
Piperacillin sodium is derived from D(-)-α-aminobenzylpenicillin.

Tazobactam (as sodium).

Chemical name: sodium (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid 4,4-dioxide.
Structural formula:
Molecular formula: C10H11N4NaO5S.
Molecular weight: 322.28.
Tazobactam sodium, a derivative of the penicillin nucleus, is a penicillanic acid sulfone.

CAS number.

Piperacillin sodium.

CAS Registry no. 59703-84-3.

Tazobactam sodium.

CAS Registry no. 89785-84-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4: Prescription Only Medicine.

Summary Table of Changes