Piperacillin + Tazobactam: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Indonesia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Bacterial infection in neutropenic patients

Adult: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
For the treatment of neutropenic patients with signs of infection (e.g. fever): In combination with aminoglycosides: 4,000 mg/500 mg 6 hourly via IV infusion over 30 minutes. Usual treatment duration: 5-14 days. Dose and treatment duration must be based on the severity of infection, pathogen(s), and individual response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).
Child: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
For the treatment of neutropenic patients with signs of infection (e.g. fever): In combination with aminoglycosides: 2-12 years 80 mg/10 mg/kg 6 hourly via IV infusion over 30 minutes. Max: 4,000 mg/500 mg per dose; >12 years Same as adult dose.

Intravenous
Hospital-acquired pneumonia

Adult: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 3,000 mg and tazobactam 375 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
Usual dose: 4,000 mg/500 mg 6 hourly or 3,000 mg/375 mg 6 hourly via IV infusion over 30 minutes. Usual treatment duration: 5-14 days. Dose and treatment duration must be based on the severity of infection, pathogen(s), and individual response. Use in combination with aminoglycosides is recommended for cases caused by Pseudomonas aeruginosa. Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).
Child: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 3,000 mg and tazobactam 375 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
2-9 months 80 mg/10 mg/kg 6 hourly via IV infusion over 30 minutes; >9 months weighing ≤40 kg: 100 mg/12.5 mg/kg 6 hourly via IV infusion over 30 minutes; >40 kg: Same as adult dose. Dose and treatment duration must be based on the severity of infection, pathogen(s), and individual response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).

Intravenous
Complicated skin and skin structure infections, Complicated urinary tract infections, Uncomplicated skin and skin structure infections, Uncomplicated urinary tract infections

Intravenous
Complicated intra-abdominal infections

Adult: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 3,000 mg and tazobactam 375 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
Usual dose: 4,000 mg/500 mg 8 hourly or 3,000 mg/375 mg 6 hourly via IV infusion over 30 minutes. Usual treatment duration: 5-14 days. Dose and treatment duration must be based on the severity of infection, pathogen(s), and individual response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).
Child: Piperacillin 2,000 mg and tazobactam 250 mg powder for solution for infusion
Piperacillin 3,000 mg and tazobactam 375 mg powder for solution for infusion
Piperacillin 4,000 mg and tazobactam 500 mg powder for solution for infusion
2-9 months For appendicitis and/or peritonitis: 80 mg/10 mg/kg 8 hourly via IV infusion over 30 minutes; >9 months For appendicitis and/or peritonitis: ≤40 kg: 100 mg/12.5 mg/kg 8 hourly via IV infusion over 30 minutes; >40 kg: Same as adult dose. Alternatively, 2-12 years 100 mg/12.5 mg/kg 8 hourly via IV infusion over 30 minutes. Max: 4,000 mg/500 mg per dose; >12 years Same as adult dose. Dose and treatment duration must be based on the severity of infection, pathogen(s), and individual response. Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).

Renal Impairment

Hospital-acquired pneumonia:
Patients undergoing haemodialysis: One additional 2,000 mg/250 mg dose must be given after each dialysis session. Alternatively, Max of 2,000 mg/250 mg 8 hourly, an additional dose of 670 mg/80 mg should be given following each dialysis on haemodialysis days.

CrCl (mL/min)	Dosage
<20	2,000 mg/250 mg 6 hourly or 4,000 mg/500 mg 12 hourly.
20-40	3,000 mg/375 mg 6 hourly or 4,000 mg/500 mg 8 hourly.

Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).

Bacterial infection in neutropenic patients:
Patients undergoing haemodialysis: One additional 2,000 mg/250 mg dose must be given after each dialysis session.

CrCl (mL/min)	Dosage
<20	Max: 4,000 mg/500 mg 12 hourly.
20-40	Max: 4,000 mg/500 mg 8 hourly.

Complicated intra-abdominal infections; Complicated and uncomplicated skin and soft tissue infections; Complicated and uncomplicated urinary tract infections:
Patients undergoing haemodialysis: One additional 2,000 mg/250 mg dose must be given after each dialysis session. Alternatively, Max of 2,000 mg/250 mg 12 hourly, an additional dose of 670 mg/80 mg should be given following each dialysis on haemodialysis days.

CrCl (mL/min)	Dosage
<20	2,000 mg/250 mg 8 hourly. Max: 4,000 mg/500 mg 12 hourly.
20-40	2,000 mg/250 mg 6 hourly. Max: 4,000 mg/500 mg 8 hourly.

Dosage recommendations may vary among individual products and between countries (refer to detailed product guidelines).

Reconstitution

Powder for solution for infusion: Reconstitute a vial labelled as 2,000 mg/250 mg, 3,000 mg/375 mg and 4,000 mg/500 mg with 10 mL, 15 mL and 20 mL of diluent (e.g. sterile water for inj, dextrose 5% in water, NaCl 0.9% solution), respectively. Adult and children >40 kg: Further dilute the reconstituted solution with compatible IV solution (e.g. dextrose 5% in water, NaCl 0.9% solution) to a volume of 50-150 mL. Children ≤40 kg and neonates: Further dilute the reconstituted solution with a compatible IV solution to a final concentration of 20-80 mg/mL piperacillin and 2.5-10 mg/mL tazobactam. Reconstitute and dilute piperacillin + tazobactam and the aminoglycoside separately when concomitantly used.

Incompatibility

Incompatible with aminoglycosides (in the same syringe or IV fluid container), blood products or albumin hydrolysates, solutions containing Na bicarbonate and Lactated Ringer's solution. Only those piperacillin + tazobactam preparations formulated with edetate disodium dihydrate (EDTA) are compatible with Lactated Ringer's solution for coadministration via Y-site infusion.

Contraindications

Hypersensitivity to piperacillin, tazobactam, β-lactamase inhibitors and history of severe allergic reactions to β-lactams (e.g. cephalosporins, carbapenems, monobactams).

Special Precautions

Patient with cystic fibrosis, previous CNS disease, including history of seizure disorder. Neonates and children. Renal impairment, including haemodialysis patients. Pregnancy and lactation.

Adverse Reactions

Significant: Bone marrow suppression (e.g. neutropenia, leucopenia, agranulocytosis, pancytopenia), drug-induced thrombocytopenia, bleeding events, nephrotoxicity, piperacillin-induced encephalopathy, bacterial or fungal superinfection.
Gastrointestinal disorders: Diarrhoea, constipation, nausea, vomiting, dyspepsia, abdominal pain.
General disorders and administration site conditions: Inj site reactions, chills, fever.
Hepatobiliary disorders: Jaundice, hepatitis.
Infections and infestations: Candidiasis.
Investigations: Increased AST/ALT, blood alkaline phosphatase, blood creatinine, BUN; prolonged aPTT, decreased blood albumin and total protein.
Metabolism and nutrition disorders: Hypoglycaemia, hypokalaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Nervous system disorders: Headache.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Eosinophilic pneumonia. Rarely, epistaxis.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Hypotension, flushing, phlebitis, thrombophlebitis.
Potentially Fatal: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, and severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms); Clostridioides difficile-associated diarrhoea, Clostridioides difficile colitis; haemophagocytic lymphohistiocytosis.

Pregnancy Category (US FDA)

Parenteral: B

Monitoring Parameters

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Evaluate the patient's allergy history before treatment initiation. Monitor creatinine, BUN, urinalysis, LFTs, serum electrolytes, and haematologic parameters (e.g. CBC with differential, prothrombin time) periodically with prolonged therapy. Closely assess for signs of anaphylaxis (during initial dose), bleeding, skin rash, and CNS effects.

Overdosage

Symptoms: Nausea, vomiting, diarrhoea, neuromuscular excitability or convulsions dose. Management: Symptomatic and supportive treatment. Haemodialysis may reduce excessive serum concentrations.

Drug Interactions

Increased incidence of nephrotoxicity or acute kidney injury when given with vancomycin. Prolonged half-life and decreased renal clearance with probenecid.
Piperacillin: May prolong the neuromuscular blockade of vecuronium. May reduce the excretion and increase the serum levels of methotrexate. May enhance the anticoagulant effects of heparin and oral anticoagulants.

Lab Interference

May lead to a false-positive result with Platelia Aspergillus enzyme immunoassay (EIA) test.
Piperacillin: May cause a positive direct Coombs direct test. May cause false-positive results for urine glucose tests using the copper reduction method.

Action

Description:
Mechanism of Action: Piperacillin is a broad-spectrum ureidopenicillin that inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls by binding to 1 or more of the penicillin-binding proteins (PBPs), thereby inhibiting bacterial septum formation and cell wall biosynthesis.
Tazobactam is a penicillanic acid sulfone derivative that irreversibly inhibits certain bacterial β-lactamases, thereby protecting piperacillin from degradation. It enhances the piperacillin spectrum of activity to include some β-lactamase-producing bacteria.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: Immediate or in 1-2 hours after completion of 30-minute IV infusion.
Distribution: Widely distributed into body tissues and fluids, including the lungs, intestinal mucosa, uterus, ovary, fallopian tube, gallbladder, interstitial fluid, and bile. Poor penetration into the CSF (except when the meninges are inflamed).
Piperacillin: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.243 L/kg. Plasma protein binding: Approx 26-33%.
Tazobactam: Crosses the placenta. Plasma protein binding: 31-32%.
Metabolism: Piperacillin: Metabolised to form a desethyl metabolite (weak activity).
Tazobactam: Metabolised into an inactive metabolite.
Excretion: Piperacillin: Via urine (68% as unchanged drug); faeces (10-20%). Elimination half-life: 0.7-1.2 hours.
Tazobactam: Via urine (80% as unchanged drug, the remainder as inactive metabolite). Elimination half-life: 0.7-0.9 hours.

Chemical Structure

Storage

Intact vial: Store between 20-25°C. Reconstituted solution: Store between 20-25°C for up to 24 hours or 2-8°C for up to 48 hours. Do not freeze. Diluted solution: Stable for up to 24 hours when stored between 2-8°C. Premixed frozen solution: Store at or below -20°C. Thawed solution is stable between 2-8°C for 14 days or between 20-25°C for 24 hours. Do not refreeze. Storage and stability recommendations may vary between individual products or countries (refer to detailed product guidelines).

MIMS Class

Penicillins

ATC Classification

J01CR05 - piperacillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

References

Cohen-Wolkowiez M, Watt KM, Zhou C et al. Developmental Pharmacokinetics of Piperacillin and Tazobactam Using Plasma and Dried Blood Spots from Infants. Antimicrobial Agents and Chemotherapy. 2014 May;58(5):2856-2865. doi:10.1128/AAC.02139-13. Accessed 10/05/2023

Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. "Tables of Antibacterial Drug Dosages", Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics [online]. Accessed 10/05/2023.

AFT Pharmaceuticals Limited. PipTaz-AFT Powder for Injection data sheet September 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 10/05/2023.

Anon. Piperacillin and Tazobactam (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/05/2023.

Anon. Piperacillin and Tazobactam Sodium. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/05/2023.

Anon. Piperacillin/Tazobactam. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 10/05/2023.

Buckingham R (ed). Piperacillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/05/2023.

Buckingham R (ed). Tazobactam Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/05/2023.

Joint Formulary Committee. Piperacillin with Tazobactam. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/05/2023.

Paediatric Formulary Committee. Piperacillin with Tazobactam. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 10/05/2023.

Piperacillin and Tazobactam Injection, Powder for Solution (Shandong Anxin Pharmaceutical Co., Ltd). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/05/2023.

Piperacillin/Tazobactam 2 g/0.25 g Powder for Solution for Infusion (Genus Pharmaceuticals Ltd. [trading as STADA]). MHRA. https://products.mhra.gov.uk. Accessed 10/05/2023.

Piperacillin/Tazobactam 4 g/0.5 g Powder for Solution for Infusion (Noridem Enterprises Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 10/05/2023.

Piperacillin; Tazobactam. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 10/05/2023.

Tazocin EF (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 10/05/2023.

Zosyn Injection, Solution (Baxter Healthcare Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/05/2023.

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