Drugs List

Therapeutic Indications

Uses

Bacterial infection in neutropenic adult/child given with an aminoglycoside
Complicated urinary tract infections
Infections intra-abdominal
Pneumonia
Septicaemia
Soft tissue infections
Treatment of skin and skin structure infections

Treatment is indicated for infections in adults and children over 2 years of age.

Severe pneumonia including hospital-acquired and ventilator-associated pneumonia.
Complicated urinary tract infections (including Pyelonephritis)
Complicated intra-abdominal infections
Complicated skin and soft tissue infections (including diabetic foot infections)
Bacterial infections in neutropenic patients.

Administration

For intravenous administration.

The dose should be given by intravenous infusion over 30 minutes.

Contraindications

Long QT syndrome
Torsade de pointes

Precautions and Warnings

Allergic disposition
Children under 2 years
Family history of long QT syndrome
Restricted sodium intake
Breastfeeding
Cystic fibrosis
Electrolyte imbalance
Haemodialysis
History of torsade de pointes
Hypokalaemia
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Sodium content of formulation may be significant
Advise patient ability to drive or operate machinery may be impaired
Before initiating therapy enquire about previous hypersensitivity reactions
Consult national/regional policy on the use of anti-infectives
Not all available products are licensed for all uses
Some brands contain EDTA which may deplete zinc stores after prolonged use
Do not mix with other drugs/substances unless compatibility known
Have adrenaline injection ready for use in case of anaphylaxis
Consider monitoring ECG in patients at risk of QT prolongation
Haematological monitoring required in long term use
Monitor hepatic function on long term therapy
Monitor potassium in patients with low potassium reserve
Monitor renal function on long term therapy
Monitor serum electrolytes
Monitor skin changes
Monitor toxicity - discontinue or modify dose if necessary
Consider pseudomembranous colitis if patient presents with diarrhoea
Superinfection may occur during therapy
May affect results of some laboratory tests
Discontinue at once if pseudomembranous colitis occurs
Discontinue drug if bleeding abnormalities occur
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if skin reactions persist

Bleeding abnormalities have occurred in some patients. These have 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 abnormalities occur, the antibiotic should be discontinued and appropriate therapy initiated.

Neuromuscular excitability or convulsions can occur if higher than recommended doses are given intravenously, especially in patients with impaired renal function.

Caution should be exercised in patients with low potassium reserves or those taking concurrent potassium lowering medications, as hypokalaemia may occur. In these patients, electrolyte levels should be monitored regularly. A modest rise in indices of hepatic function may be seen with therapy.

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

Pregnancy and Lactation

Pregnancy

Use piperacillin/tazobactam with caution in pregnancy.

Both piperacillin and tazobactam cross the human placenta. Piperacillin/tazobactam should only be used in pregnant women when the expected benefit outweighs the risk to the mother and foetus.

There have been no reports linking the use of piperacillin to congenital defects in humans, however, there are no adequate and well controlled studies available. Studies in animals have shown developmental toxicity. The combination of piperacillin/tazobactam is considered relatively safe for use during pregnancy.

Penicillins alone can be safely used (at usual doses) during pregnancy and are the antibiotics of choice in this indication. However, beta-lactamase inhibitors should only be used in pregnancy when strongly indicated e.g. where penicillins alone have been ineffective.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use piperacillin/tazobactam with caution in breastfeeding.

Piperacillin/tazobactam are excreted into the breast milk in low concentrations. Piperacillin/tazobactam should only be used in breastfeeding women when the expected benefit outweighs the risk to the mother and foetus.

Penicillins are the antibiotics of choice during breastfeeding. However, there is little information available on the use of piperacillin with tazobactam. The effects of these low concentrations are thought to present little complications to the infant. However, the clinician should anticipate disruptions of the infants gastrointestinal microflora, possibly leading to diarrhoea or thrush.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal bleeding
Agranulocytosis
Altered consciousness
Anaemia
Anaphylaxis
Antibiotic-associated colitis
Arthralgia
Bullous dermatoses
Coagulation disorders
Constipation
Convulsions
Diarrhoea
Dry mouth
Dyspepsia
Eczema
Encephalopathy
Eosinophilia
Epistaxis
Erythema
Erythema multiforme
Exanthema
Fever
Flushing
Gamma glutamyl transferase (GGT) increased
Haemolytic anaemia
Hallucinations
Headache
Hepatitis
Hypersensitivity reactions
Hypoalbuminaemia
Hypoglycaemia
Hypokalaemia
Hypoproteinaemia
Hypotension
Increase in alkaline phosphatase
Increase in ALT level
Increase in AST level
Increase in blood urea nitrogen
Increased partial thromboplastin time
Increased sweating
Injection site reactions
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Muscle weakness
Myalgia
Myoclonus
Nausea
Neutropenia
Oedema
Pancytopenia
Phlebitis
Positive Coombs test
Prolonged bleeding
Prothrombin time increased
Pruritus
Pseudomembranous colitis
Purpura
Rash
Renal failure
Rigors
Serum bilirubin increased
Serum creatinine increased
Shock
Stevens-Johnson syndrome
Stomatitis
Superinfections
Thrombocytopenia
Thrombocytosis
Thrombophlebitis
Tiredness
Toxic epidermal necrolysis
Urticaria
Vomiting

Presentation

Powder for solution for infusion containing piperacillin and tazobactam.

Drugs List

Therapeutic Indications

Uses

Bacterial infection in neutropenic adult/child given with an aminoglycoside
Complicated urinary tract infections
Infections intra-abdominal
Pneumonia
Septicaemia
Soft tissue infections
Treatment of skin and skin structure infections

Treatment is indicated for infections in adults and children over 2 years of age.

Severe pneumonia including hospital-acquired and ventilator-associated pneumonia.
Complicated urinary tract infections (including Pyelonephritis)
Complicated intra-abdominal infections
Complicated skin and soft tissue infections (including diabetic foot infections)
Bacterial infections in neutropenic patients.

Dosage

Adults

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For intravenous administration.

The dose should be given by intravenous infusion over 30 minutes.

Contraindications

Long QT syndrome
Torsade de pointes

Precautions and Warnings

Allergic disposition
Children under 2 years
Family history of long QT syndrome
Restricted sodium intake
Breastfeeding
Cystic fibrosis
Electrolyte imbalance
Haemodialysis
History of torsade de pointes
Hypokalaemia
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Sodium content of formulation may be significant
Advise patient ability to drive or operate machinery may be impaired
Before initiating therapy enquire about previous hypersensitivity reactions
Consult national/regional policy on the use of anti-infectives
Not all available products are licensed for all uses
Some brands contain EDTA which may deplete zinc stores after prolonged use
Do not mix with other drugs/substances unless compatibility known
Have adrenaline injection ready for use in case of anaphylaxis
Consider monitoring ECG in patients at risk of QT prolongation
Haematological monitoring required in long term use
Monitor hepatic function on long term therapy
Monitor potassium in patients with low potassium reserve
Monitor renal function on long term therapy
Monitor serum electrolytes
Monitor skin changes
Monitor toxicity - discontinue or modify dose if necessary
Consider pseudomembranous colitis if patient presents with diarrhoea
Superinfection may occur during therapy
May affect results of some laboratory tests
Discontinue at once if pseudomembranous colitis occurs
Discontinue drug if bleeding abnormalities occur
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if skin reactions persist

Bleeding abnormalities have occurred in some patients. These have 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 abnormalities occur, the antibiotic should be discontinued and appropriate therapy initiated.

Neuromuscular excitability or convulsions can occur if higher than recommended doses are given intravenously, especially in patients with impaired renal function.

Caution should be exercised in patients with low potassium reserves or those taking concurrent potassium lowering medications, as hypokalaemia may occur. In these patients, electrolyte levels should be monitored regularly. A modest rise in indices of hepatic function may be seen with therapy.

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

Pregnancy and Lactation

Pregnancy

Use piperacillin/tazobactam with caution in pregnancy.

Both piperacillin and tazobactam cross the human placenta. Piperacillin/tazobactam should only be used in pregnant women when the expected benefit outweighs the risk to the mother and foetus.

There have been no reports linking the use of piperacillin to congenital defects in humans, however, there are no adequate and well controlled studies available. Studies in animals have shown developmental toxicity. The combination of piperacillin/tazobactam is considered relatively safe for use during pregnancy.

Penicillins alone can be safely used (at usual doses) during pregnancy and are the antibiotics of choice in this indication. However, beta-lactamase inhibitors should only be used in pregnancy when strongly indicated e.g. where penicillins alone have been ineffective.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use piperacillin/tazobactam with caution in breastfeeding.

Piperacillin/tazobactam are excreted into the breast milk in low concentrations. Piperacillin/tazobactam should only be used in breastfeeding women when the expected benefit outweighs the risk to the mother and foetus.

Penicillins are the antibiotics of choice during breastfeeding. However, there is little information available on the use of piperacillin with tazobactam. The effects of these low concentrations are thought to present little complications to the infant. However, the clinician should anticipate disruptions of the infants gastrointestinal microflora, possibly leading to diarrhoea or thrush.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal bleeding
Agranulocytosis
Altered consciousness
Anaemia
Anaphylaxis
Antibiotic-associated colitis
Arthralgia
Bullous dermatoses
Coagulation disorders
Constipation
Convulsions
Diarrhoea
Dry mouth
Dyspepsia
Eczema
Encephalopathy
Eosinophilia
Epistaxis
Erythema
Erythema multiforme
Exanthema
Fever
Flushing
Gamma glutamyl transferase (GGT) increased
Haemolytic anaemia
Hallucinations
Headache
Hepatitis
Hypersensitivity reactions
Hypoalbuminaemia
Hypoglycaemia
Hypokalaemia
Hypoproteinaemia
Hypotension
Increase in alkaline phosphatase
Increase in ALT level
Increase in AST level
Increase in blood urea nitrogen
Increased partial thromboplastin time
Increased sweating
Injection site reactions
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Muscle weakness
Myalgia
Myoclonus
Nausea
Neutropenia
Oedema
Pancytopenia
Phlebitis
Positive Coombs test
Prolonged bleeding
Prothrombin time increased
Pruritus
Pseudomembranous colitis
Purpura
Rash
Renal failure
Rigors
Serum bilirubin increased
Serum creatinine increased
Shock
Stevens-Johnson syndrome
Stomatitis
Superinfections
Thrombocytopenia
Thrombocytosis
Thrombophlebitis
Tiredness
Toxic epidermal necrolysis
Urticaria
Vomiting

Effects on Laboratory Tests

False-positives have been seen in urine tests for glucose using a copper reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions should be used.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving piperacillin-tazobactam infusion 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 piperacillin-tazobactam should be interpreted cautiously and confirmed by other diagnostic methods.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2018.

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Piperacillin/Tazobactam 2g/0.25 g Powder for Solution for Infusion. Wockhardt UK Ltd. Revised July 2017.
Summary of Product Characteristics: Piperacillin/Tazobactam 4g/0.5 g Powder for Solution for Infusion. Wockhardt UK Ltd. Revised July 2017.
Summary of Product Characteristics: Tazocin 2g/0.25g and 4g/0.5g Powder for Solution for Infusion. Pfizer Limited. Revised August 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 September 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Piperacillin and Tazobactam Last revised: February 12, 2010
Last accessed: May 20, 2011.