Piperacillin and tazobactam is a combination medicine containing piperacillin, a penicillin-class antibacterial, and tazobactam, a beta-lactamase inhibitor. It is indicated for the treatment of moderate to severe infections caused by susceptible bacteria in the following conditions:

Intra-abdominal infections: Including appendicitis complicated by rupture or abscess, and peritonitis caused by beta-lactamase-producing isolates of Escherichia coli or members of the Bacteroides fragilis group, such as B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus.

Skin and skin structure infections: Including uncomplicated and complicated skin and soft tissue infections such as cellulitis, cutaneous abscesses, and ischemic or diabetic foot infections caused by beta-lactamase-producing isolates of Staphylococcus aureus.

Female pelvic infections: Including postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase-producing isolates of Escherichia coli.

Community-acquired pneumonia: Moderate community-acquired pneumonia caused by beta-lactamase-producing isolates of Haemophilus influenzae.

Nosocomial pneumonia: Moderate to severe hospital-acquired pneumonia caused by beta-lactamase-producing isolates of Staphylococcus aureus and piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia caused by Pseudomonas aeruginosa should be treated in combination with an aminoglycoside.

Piperacillin is a broad-spectrum, semi-synthetic penicillin that is active against many gram-positive and gram-negative aerobic and anaerobic bacteria. It exerts its bactericidal effect by inhibiting septum formation and bacterial cell wall synthesis. Tazobactam is a potent inhibitor of many beta-lactamases, including both plasmid-mediated and chromosomally mediated enzymes that commonly cause resistance to penicillins. It enhances and broadens the antibacterial spectrum of piperacillin by enabling it to act against many beta-lactamase-producing bacteria that would otherwise be resistant. Therefore, this infusion combines the action of a broad-spectrum antibiotic with that of a beta-lactamase inhibitor.

Piperacillin and tazobactam should be administered by intravenous infusion over 30 minutes

Adult Patients: The usual total daily dose of Piperacillin and tazobactam for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam). The usual duration of treatment is from 7 to 10 days.

Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). The recommended duration of the treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeroginosa is isolated.

Pediatric Patients: For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended dosage based on Pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam dosage in pediatric patients with renal impairment.

Aminoglycosides: Piperacillin may inactivate aminoglycosides by converting them into microbiologically inactive amides. In patients with end-stage renal disease who require hemodialysis, concurrent use of aminoglycosides with piperacillin may significantly reduce aminoglycoside concentrations, especially tobramycin; therefore, monitoring is recommended.

Sequential administration of piperacillin and tazobactam with tobramycin in patients with normal renal function or mild to moderate renal impairment has been shown to cause a modest reduction in serum tobramycin levels; however, dosage adjustment is generally not considered necessary.

Probenecid: When given together with piperacillin and tazobactam, probenecid prolongs the half-life of piperacillin by 21% and that of tazobactam by 71%, due to inhibition of their tubular renal secretion. Probenecid should not be used concomitantly with piperacillin and tazobactam unless the expected benefit outweighs the potential risk.

Anticoagulants: During concurrent use of high doses of heparin, oral anticoagulants, or other drugs that may affect blood coagulation or platelet function, coagulation parameters should be checked more frequently and monitored regularly.

Vecuronium: Concomitant use of piperacillin with vecuronium has been associated with prolonged neuromuscular blockade of vecuronium. Piperacillin and tazobactam may produce a similar effect when administered together with vecuronium. Due to their similar mechanism of action, the neuromuscular blockade produced by any non-depolarizing muscle relaxant may be prolonged in the presence of piperacillin.

Methotrexate: Limited data suggest that co-administration of methotrexate and piperacillin may reduce methotrexate clearance because of competition for renal secretion. The effect of tazobactam on methotrexate elimination has not been established. If concurrent therapy is necessary, serum methotrexate levels and signs and symptoms of methotrexate toxicity should be monitored frequently.

Piperacillin and tazobactam is contraindicated in patients with a history of hypersensitivity or allergic reactions to any penicillins, cephalosporins, or beta-lactamase inhibitors.

Adverse reactions mainly involve the skin, including rash, itching (pruritus), and purpura. Gastrointestinal effects may include diarrhoea, constipation, nausea, vomiting, dyspepsia, and abdominal pain. General disorders and administration site reactions include fever, injection site reactions (≤1%), and rigors (≤1%). Immune system reactions may include hypersensitivity and anaphylactic or anaphylactoid reactions, including shock (≤1%). Infections such as candidiasis and pseudomembranous colitis (≤1%) have been reported. Metabolic and nutritional disorders may include hypoglycaemia (≤1%). Musculoskeletal and connective tissue disorders include muscle pain (myalgia) and joint pain (arthralgia) (≤1%). Psychiatric disorders such as insomnia may occur. Vascular disorders include phlebitis, thrombophlebitis (≤1%), hypotension (≤1%), and flushing (≤1%). Respiratory, thoracic, and mediastinal disorders may include epistaxis (≤1%).

Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data in pregnant women to determine the drug-associated risk of major birth defects or miscarriage. Piperacillin is excreted in human milk, but the presence of tazobactam in human milk has not been adequately studied. There is also no sufficient information on the effects of piperacillin and tazobactam on the breastfed infant or on milk production.

Serious hypersensitivity reactions, including anaphylactic and anaphylactoid reactions, have been reported in patients receiving piperacillin and tazobactam. If such a reaction occurs, treatment should be discontinued immediately.

Piperacillin and tazobactam may also cause severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The drug should be discontinued if progressive rash develops. Hematological effects, including bleeding, leukopenia, and neutropenia, have also been reported. Hematologic tests should be monitored during prolonged therapy.

Nephrotoxicity has been observed in critically ill patients. In such patients, piperacillin and tazobactam has been identified as an independent risk factor for renal failure and delayed recovery of renal function compared with other beta-lactam antibacterial agents. Therefore, alternative treatment options should be considered in critically ill patients when appropriate. If no suitable alternative is available, renal function should be monitored during treatment. Patients who develop diarrhoea during treatment should be evaluated for Clostridium difficile-associated diarrhoea.

Pediatric Use: The use of piperacillin and tazobactam in pediatric patients aged 2 months and older with appendicitis and/or peritonitis is supported by evidence from well-controlled clinical studies and pharmacokinetic data from both adults and children. However, appropriate dose adjustment in pediatric patients with renal impairment has not yet been established.

Geriatric Use: Patients over 65 years of age are not at increased risk of adverse effects solely due to age. However, dose adjustment may be necessary in the presence of renal impairment. This may be clinically important, particularly in conditions such as congestive heart failure.

Renal Impairment: In patients with creatinine clearance of 40 mL/min or less, and in patients undergoing dialysis (including hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam should be reduced according to the degree of renal impairment.

Hepatic Impairment: Dose adjustment of piperacillin and tazobactam is not required in patients with hepatic cirrhosis.

Patients with Cystic Fibrosis: As with other semisynthetic penicillins, treatment with piperacillin has been associated with an increased incidence of fever and rash in patients with cystic fibrosis.

Post-marketing reports of overdose with piperacillin/tazobactam have been documented. Most reported symptoms, including nausea, vomiting, and diarrhoea, have also been observed at the usual recommended doses. If higher than recommended intravenous doses are administered, especially in patients with renal failure, neuromuscular excitability or convulsions may occur. Management of overdose should be supportive and symptomatic, based on the patient’s clinical condition.

Broad-spectrum penicillins; other beta-lactam antibiotics.

Store below 30°C, protected from light and moisture. Keep out of the reach of children.