Piperacillin and Tazobactam interacts in the following cases:
The intravenous dose should be adjusted to the degree of actual renal impairment (each patient must be monitored closely for signs of substance toxicity; medicinal product dose and interval should be adjusted accordingly):
| Creatinine clearance (ml/min) | Piperacillin/Tazobactam (recommended dose) |
| >40 | No dose adjustment necessary |
| 20-40 | Maximum dose suggested: 4 g/0.5 g every eight hours |
| <20 | Maximum dose suggested: 4 g/0.5 g every 12 hours |
For patients on haemodialysis, one additional dose of Piperacillin/Tazobactam 2g/0.25g should be administered following each dialysis period, because haemodialysis removes 30%-50% of piperacillin in four hours.
The intravenous dose should be adjusted to the degree of actual renal impairment as follows (each patient must be monitored closely for signs of substance toxicity; medicinal product dose and interval should be adjusted accordingly):
| Creatinine clearance (ml/min) | Piperacillin/Tazobactam (recommended dose) |
| >50 | No dose adjustment needed. |
| ≤50 | 70 mg piperacillin/8.75 mg tazobactam/kg every eight hours. |
For children on haemodialysis, one additional dose of 40 mg piperacillin/5 mg tazobactam/kg should be administered following each dialysis period.
During simultaneous administration of heparin, oral anticoagulants and other drugs that may affect the blood coagulation system including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly.
As with other penicillins, concurrent administration of probenecid and piperacillin/tazobactam produces a longer half-life and lower renal clearance for both piperacillin and tazobactam; however, peak plasma concentrations of either substances are unaffected.
No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin.
However, a limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/tazobactam and vancomycin as compared to vancomycin alone.
Non-enzymatic methods of measuring urinary glucose may lead to false-positive results, as with other penicillins. Therefore, enzymatic urinary glucose measurement is required under piperacillin/tazobactam therapy.
A number of chemical urine protein measurement methods may lead to false-positive results. Protein measurement with dip sticks is not affected.
The direct Coombs test may be positive.
Bio-Rad Laboratories Platelia Aspergillus EIA tests may lead to false-positive results for patients receiving piperacillin/tazobactam. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported.
Positive test results for the assays listed above in patients receiving piperacillin/tazobactam should be confirmed by other diagnostic methods.
There are no or a limited amount of data from the use of piperacillin/tazobactam in pregnant women. Studies in animals have shown developmental toxicity, but no evidence of teratogenicity, at doses that are maternally toxic. Piperacillin and tazobactam cross the placenta. Piperacillin/tazobactam should only be used during pregnancy if clearly indicated, i.e. only if the expected benefit outweighs the possible risks to the pregnant woman and foetus.
Piperacillin is excreted in low concentrations in breast milk; tazobactam concentrations in human milk have not been studied. Women who are breast-feeding should be treated only if the expected benefit outweighs the possible risks to the woman and child.
A fertility study in rats showed no effect on fertility and mating after intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam.
No studies on the effects on the ability to drive and use machines have been performed.
The most commonly reported adverse reaction is diarrhoea (occurring in 1 patient out of 10) are diarrhoea, nausea, vomiting and rash.
Among the most serious adverse reactions pseudo-membranous colitis and toxic epidermal necrolysis occur in 1 to 10 patients in 10,000. The frequencies for pancytopenia, anaphylactic shock and Stevens-Johnson syndrome cannot be estimated from the currently available data.
In the following table, adverse reactions are listed by system organ class and MedDRA-preferred term. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
| System Organ Class | Very common ≥1/10 | Common ≥1/100 to <1/10 | Uncommon ≥1/1,000 to <1/100 | Rare ≥1/10,000 to <1/1,000 | Frequency not known (cannot be estimated from available data) |
| Infections and infestations | candidiasis* | pseudomembranous colitis | |||
| Blood and lymphatic system disorders | thrombocytopenia, anaemia* | leukopenia | agranulocytosis | pancytopenia*, neutropenia, haemolytic anaemia*, eosinophilia*, thrombocytosis* | |
| Immune system disorders | anaphylactoid reaction*, anaphylactic reaction*, anaphylactoid shock*, anaphylactic shock*, hypersensitivity* | ||||
| Metabolism and nutrition disorders | hypokalaemia | ||||
| Psychiatric disorders | insomnia | delirium* | |||
| Nervous system disorders | headache, insomnia | ||||
| Vascular disorders | hypotension, thrombophlebitis, phlebitis, flushing | ||||
| Respiratory, thoracic and mediastinal disorders | epistaxis | eosinophilic pneumonia | |||
| Gastrointestinal disorders | diarrhoea | abdominal pain, vomiting, nausea, constipation, dyspepsia | stomatitis | ||
| Hepatobiliary disorders | hepatitis*, jaundice | ||||
| Skin and subcutaneous tissue disorders | rash, pruritus | erythema multiforme*, urticaria, rash maculopapular* | toxic epidermal necrolysis* | Stevens-Johnson syndrome*, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms (DRESS)*, acute generalised exanthematous pustulosis (AGEP)*, dermatitis bullous purpura | |
| Musculoskeletal and connective tissue disorders | arthralgia, myalgia | ||||
| Renal and urinary disorders | renal failure, tubulointerstitial nephritis* | ||||
| General disorders and administration site conditions | pyrexia, injection site reaction | chills | |||
| Investigations | alanine aminotransferase increased, aspartate aminotransferase increased, protein total decreased, blood albumin decreased, Coombs direct test positive, blood creatinine increased, blood alkaline phosphatase increased, blood urea increased, activated partial thromboplastin time prolonged | blood glucose decreased, blood bilirubin increased, prothrombin time prolonged | bleeding time prolonged, gamma- glutamyltransferase increased |
* ADR identified post marketing
Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
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