Piperacillin + Tazobactam

Intravenous
Empiric therapy for febrile neutropenic patients

Intravenous
Nosocomial pneumonia

Intravenous
Complicated intra-abdominal infections

Intravenous
Complicated urinary tract infections, Skin and soft tissue infections

Nosocomial pneumonia:
Haemodialysis patients: 2.25 g 8 hrly; additional dose of 0.75 g after each dialysis session. CAPD: 2.25 g 8 hrly.

CrCl (mL/min)	Dosage
<20	2.25 g 6 hrly.
20-40	3.375 g 6 hrly.

Empiric therapy for febrile neutropenic patients; Complicated intra-abdominal infections; Complicated urinary tract infections; Skin and soft tissue infections:
Haemodialysis patients: 2.25 g 12 hrly; additional dose of 0.75 g after each dialysis session. CAPD: 2.25 g 12 hrly.

CrCl (mL/min)	Dosage
<20	2.25 g 8 hrly.
20-40	2.25 g 6 hrly.

Reconstitute initially (2.25 g in 10 mL, 4.5 g in 20 mL) w/ water for inj, glucose 5% or NaCl 0.9%, then further dilute to 50-150 mL w/ compatible infusion soln.

Y-site: Aciclovir, amiodarone, amphotericin B cholesteryl sulfate complex, amphotericin B, azithromycin, chlorpromazine, cisplatin, dacarbazine, daunorubicin, dobutamine, doxorubicin liposome, doxorubicin, EDTA formulated product (caspofungin, pantoprazole and tobramycin), doxycycline, droperidol, famotidine, ganciclovir, gemcitabine, haloperidol, hydroxyzine, idarubicin, minocycline, mitomycin, mitoxantrone, nalbuphine, prochlorperazine edisylate, promethazine, streptozocin.

Hypersensitivity to piperacillin, tazobactam or any other penicillin-antibacterial agent. History of acute severe allergic reaction to any other β-lactam active substances (e.g. cephalosporin, monobactam or carbapenem).

Patient w/ cystic fibrosis, history of seizure disorder. Renal impairment. Childn. Pregnancy and lactation.

GI effects (e.g. diarrhoea, nausea, constipation), rash (maculopapular, bullous, urticarial, eczemoid), pruritus, fever, headache, insomnia; adverse reactions at inj site (phlebitis, pain, inflammation, thrombophlebitis, oedema). Decreases in Hb and haematocrit, thrombocytopenia, increases in platelet count, transient eosinophilia, leucopenia, neutropenia; positive Coombs’ test results, prolonged prothrombin time and partial thromboplastin time. Increases in serum concentrations of creatinine and BUN, changes in serum electrolytes, transient increases in AST, ALT, alkaline phosphatase and bilirubin.
Potentially Fatal: Serious, anaphylactic reactions, antibiotic-induced pseudomembranous colitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Parenteral: B

Assess hematopoietic function periodically. Perform periodic electrolyte determinations in patients w/ low K reserves. Monitor creatinine, BUN, CBC w/ differential, prothrombin time, partial thromboplastin time, LFTs, urinalysis, signs of bleeding, signs of anaphylaxis during 1st dose.

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

Interacts w/ high doses of heparin, oral anticoagulants or other drugs that affect blood coagulation or thrombocyte function. Prolongs the neuromuscular blockade of vecuronium and non-depolarising muscle relaxants. Prolongs half-lives w/ probenecid. Increased risk of methotrexate toxicity.

May lead to false-positive results in Bio-Rad Laboratories Platelia Aspergillus EIA tests and also in urinary glucose determinations w/ tests that use copper reduction.

Description: Piperacillin inhibits bacterial septum formation and cell wall synthesis in susceptible bacteria. Tazobactam is a penicillanic acid sulfone derivative w/ β-lactamase inhibitory properties. In combination, tazobactam enhances the activity of piperacillin against β-lactamase-producing bacteria. Piperacillin and tazobactam has a wide range of activity and is active against gm+ve and gm-ve aerobic and anaerobic bacteria.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: Immediately after completion of IV infusion.
Distribution: Widely distributed into body tissues and fluids; both cross the placenta; distributed into milk (piperacillin). Plasma protein binding: Approx 30%.
Metabolism: Piperacillin: Metabolised to a desethyl metabolite. Tazobactam: Metabolised to a single metabolite that lacks pharmacological and antibacterial activities.
Excretion: Via kidney by glomerular filtration and tubular secretion as unchanged in urine, 68% (piperacillin) and 80% (tazobactam). Plasma half-life: 0.7-1.2 hr.

Source: National Center for Biotechnology Information. PubChem Database. Piperacillin, CID=43672, https://pubchem.ncbi.nlm.nih.gov/compound/Piperacillin (accessed on Jan. 22, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Tazobactam, CID=123630, https://pubchem.ncbi.nlm.nih.gov/compound/Tazobactam (accessed on Jan. 22, 2020)

Powd for inj: Store between 20-25°C. Reconstituted soln: Store between 2-8°C (for up to 48 hr) or 20-25°C (for up to 24 hr).

Penicillins

Anon. Piperacillin and Tazobactam Sodium. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 22/06/2015.

Joint Formulary Committee. Piperacillin with Tazobactam. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/06/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Piperacillin Sodium and Tazobactam Sodium. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 22/06/2015.

Piperacillin Sodium and Tazobactam Sodium Injection, Powder for Solution (Mylan Institutional LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/06/2015.