Piperacillin and Tazobactam and Sodium Chloride

1 INDICATIONS AND USAGE Piperacillin and Tazobactam for Injection and Sodium Chloride Injection, is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of: Intra-abdominal infections in adult and pediatric patients 2 months of age and older ( 1.1 ) Nosocomial pneumonia in adult and pediatric patients 2 months of age and older ( 1.2 ) Skin and skin structure infections in adults ( 1.3 ) Female pelvic infections in adults ( 1.4 ) Community-acquired pneumonia in adults ( 1.5 ) Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and other antibacterial drugs, Piperacillin and Tazobactam for Injection and Sodium Chloride Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.6 ) 1.1 Intra-abdominal Infections Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus . 1.2 Nosocomial Pneumonia Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin and tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside) [see Dosage and Administration (2) ]. 1.3 Skin and Skin Structure Infections Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is indicated in adults for the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of Staphylococcus aureus . 1.4 Female Pelvic Infections Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli . 1.5 Community-acquired Pneumonia Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae . 1.6 Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and other antibacterial drugs, Piperacillin and Tazobactam for Injection and Sodium Chloride Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION If a dose of Piperacillin and Tazobactam for Injection and Sodium Chloride injection is required that is not equal to 2.25 g, 3.375 g, or 4.5 g, this product is not recommended for use and an alternative formulation of piperacillin and tazobactam for injection should be considered ( 2.1 ). Adult Patients With Indications Other Than Nosocomial Pneumonia; The usual daily dosage of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection, for intravenous use for adults is 3.375 g every 6 ( six ) hours. ( 2.2 ) Adult Patients with Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection, for intravenous use at a dosage of 4.5 g every 6 ( six ) hours plus an aminoglycoside. (2.3 ) Adult Patients with Renal Impairment: Dosage in patients with renal impairment (creatinine clearance ≤40 mL/min) and dialysis patients should be reduced, based on the degree of renal impairment. ( 2.4 ) Pediatric Patients by Indication and Age: See Table below ( 2.5 ) Recommended Dosage of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection for Pediatric Patients 2 months of Age and Older, Weighing up to 40 Kg and With Normal Renal Function Age Appendicitis and /or Peritonitis Nosocomial Pneumonia 2 months to 9 months 90 mg/kg (80 mg piperacillin and 10 mg tazobactam) every 8 ( eight ) hours 90 mg/kg (80 mg piperacillin and 10 mg tazobactam) every 6 ( six ) hours Older than 9 months 112.5 mg/kg (100 mg piperacillin and 12.5 mg tazobactam) every 8 ( eight) hours 112.5 mg/kg (100 mg piperacillin and 12.5 mg tazobactam) every 6 ( six) hours Administer Piperacillin and Tazobactam for Injection and Sodium Chloride Injection by intravenous infusion over 30 minutes to both adult and pediatric patients 2 months of age and older. ( 2.2 , 2.3 , 2.4 , 2.5 ) Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and aminoglycosides should be reconstituted and administered separately. Co-administration via Y-site can be done under certain conditions. ( 2.7 ) See the full prescribing information for the preparation and administration instructions for Piperacillin and Tazobactam for Injection and Sodium Chloride Injection single-dose DUPLEX ® Container. 2.1 Important Administration Instructions If a dose of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is required that does not equal 2.25 g, 3.375 g, or 4.5 g, this product is not recommended for use and an alternative formulation of piperacillin and tazobactam for injection should be considered. 2.2 Recommended Dosage in Adult Patients With Indications Other Than Nosocomial Pneumonia The usual total daily dosage of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection for adult patients with indications other than nosocomial pneumonia is 3.375 g every 6 ( six ) hours, to be administered by intravenous infusion over 30 minutes. The usual duration of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection treatment is from 7 to 10 days. 2.3 Recommended Dosage in Adult Patients With Nosocomial Pneumonia Initial presumptive treatment of adult patients with nosocomial pneumonia should start with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection at a dosage of 4.5 g every 6 ( six ) hours plus an aminoglycoside, administered by intravenous infusion over 30 minutes. The recommended duration of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated. 2.4 Recommended Dosage in Adult Patients With Renal Impairment In adult patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of Piperacillin and Tazobactam …

3 DOSAGE FORMS AND STRENGTHS Piperacillin and Tazobactam for Injection USP and Sodium Chloride Injection USP is supplied as a white to off-white powder and a clear, colorless solution in a single-dose DUPLEX ® Container consisting of: 2.25 g Piperacillin and Tazobactam for Injection USP (2 g of piperacillin and 0.25 g of tazobactam) and 50 mL of 0.45% Sodium Chloride Injection USP. 3.375 g Piperacillin and Tazobactam for Injection USP (3 g of piperacillin and 0.375 g of tazobactam) and 50 mL of 0.3% Sodium Chloride Injection USP. 4.5 g Piperacillin and Tazobactam for Injection USP (4 g of piperacillin and 0.5 g of tazobactam) and 100 mL of 0.45% Sodium Chloride Injection USP. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection in a single-dose DUPLEX ® Container consisting of: 2.25 g Piperacillin and Tazobactam for Injection USP and 50 mL of 0.45% Sodium Chloride Injection USP ( 3 ) 3.375 g Piperacillin and Tazobactam for Injection USP and 50 mL of 0.3% Sodium Chloride Injection USP ( 3 ) 4.5 g Piperacillin and Tazobactam for Injection USP and 100 mL of 0.45% Sodium Chloride Injection USP ( 3 )

4 CONTRAINDICATIONS Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or betalactamase inhibitors. Patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Adverse Reactions [see Warnings and Precautions (5.1) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2) ] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5.3) ] Rhabdomyolysis [see Warnings and Precautions (5.4) ] Hematologic Adverse Reactions [see Warnings and Precautions (5.5) ] Central Nervous System Adverse Reactions [see Warnings and Precautions (5.6) ] Nephrotoxicity in Critically Ill Patients [see Warnings and Precautions (5.7) ] High Sodium Load and Electrolyte Effects [see Warnings and Precautions (5.8) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.9) ] The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache, and insomnia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-833-425-1464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection has been established from adequate and well-controlled studies of piperacillin and tazobactam. Below is a display of the adverse reactions of piperacillin and tazobactam in these adequate and well controlled studies. Clinical Trials in Adult Patients During the initial clinical investigations, 2621 patients worldwide were treated with piperacillin and tazobactam in phase 3 trials. In the key North American monotherapy clinical trials (n=830 patients), 90% of the adverse events reported were mild to moderate in severity and transient in nature. However, in 3.2% of the patients treated worldwide, piperacillin and tazobactam was discontinued because of adverse events primarily involving the skin (1.3%), including rash and pruritus; the gastrointestinal system (0.9%), including diarrhea, nausea, and vomiting; and allergic reactions (0.5%). Table 4: Adverse Reactions from Piperacillin and Tazobactam Monotherapy Clinical Trials System Organ Class Adverse Reaction Gastrointestinal disorders Diarrhea (11.3%) Constipation (7.7%) Nausea (6.9%) Vomiting (3.3%) Dyspepsia (3.3%) Abdominal pain (1.3%) General disorders and administration site conditions Fever (2.4%) Injection site reaction (≤1%) Rigors (≤1%) Immune system disorders Anaphylaxis (≤1%) Infections and infestations Candidiasis (1.6%) Pseudomembranous colitis (≤1%) Metabolism and nutrition disorders Hypoglycemia (≤1%) Musculoskeletal and connective tissue disorders Myalgia (≤1%) Arthralgia (≤1%) Nervous system disorders Headache (7.7%) Psychiatric disorders Insomnia (6.6%) Skin and subcutaneous tissue disorders Rash (4.2%, including maculopapular, bullous, and urticarial) Pruritus (3.1%) Purpura (≤1%) Vascular disorders Phlebitis (1.3%) Thrombophlebitis (≤1%) Hypotension (≤1%) Flushing (≤1%) Respiratory, thoracic and mediastinal disorders Epistaxis (≤1%) Nosocomial Pneumonia Trials Two trials of nosocomial lower respiratory tract infections were conducted. In one study, 222 patients were treated with piperacillin and tazobactam in a dosing regimen of 4.5 g every 6 hours in combination with an aminoglycoside and 215 patients were treated with imipenem/cilastatin (500 mg/500 mg every 6 hours) in combination with an aminoglycoside. In this trial, treatment-emergent adverse events were reported by 402 patients, 204 (91.9%) in the piperacillin and tazobactam group and 198 (92.1%) in the imipenem/cilastatin group. Twenty-five (11.0%) patients in the piperacillin and tazobactam group and 14 (6.5%) in the imipenem/cilastatin group (p > 0.05) discontinued treatment due to an adverse event. The second t …

7 DRUG INTERACTIONS Piperacillin and Tazobactam for Injection and Sodium Chloride Injection administration can significantly reduce tobramycin concentrations in hemodialysis patients. Monitor tobramycin concentrations in these patients. ( 7.1 ) Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be co-administered with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection unless the benefit outweighs the risk. ( 7.2 ) Co-administration of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and vancomycin. ( 7.3 ) Monitor coagulation parameters in patients receiving Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and heparin or oral anticoagulants. ( 7.4 ) Piperacillin and Tazobactam for Injection and Sodium Chloride Injection may prolong the neuromuscular blockade of vecuronium and other non-depolarizing neuromuscular blockers. Monitor for adverse reactions related to neuromuscular blockade. ( 7.5 ) 7.1 Aminoglycosides Piperacillin may inactivate aminoglycosides by converting them to microbiologically inert amides. In vivo inactivation : When aminoglycosides are administered in conjunction with piperacillin to patients with end-stage renal disease requiring hemodialysis, the concentrations of the aminoglycosides (especially tobramycin) may be significantly reduced and should be monitored. Sequential administration of piperacillin and tazobactam and tobramycin to patients with either normal renal function or mild to moderate renal impairment has been shown to modestly decrease serum concentrations of tobramycin but no dosage adjustment is considered necessary. In vitro inactivation : Due to the in vitro inactivation of aminoglycosides by piperacillin, piperacillin and tazobactam and aminoglycosides are recommended for separate administration. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and aminoglycosides should be reconstituted, and administered separately when concomitant therapy with aminoglycosides is indicated. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection, which contains EDTA, is compatible with amikacin and gentamicin for simultaneous Y-site infusion in certain diluents and at specific concentrations. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is not compatible with tobramycin for simultaneous Y-site infusion [see Dosage and Administration (2.7) ]. 7.2 Probenecid Probenecid administered concomitantly with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection prolongs the half-life of piperacillin by 21% and that of tazobactam by 71% because probenecid inhibits tubular renal secretion of both piperacillin and tazobactam. Probenecid should not be co-administered with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection unless the benefit outweighs the risk. 7.3 Vancomycin Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin and tazobactam and vancomycin as compared to vancomycin alone [see Warnings and Precautions (5.7) ]. Monitor kidney function in patients concomitantly administered with Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and vancomycin. No pharmacokinetic interactions have been noted between piperacillin and tazobactam and vancomycin. 7.4 Anticoagulants Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function [see Warnings and Precautions (5.5) ]. 7.5 Vecuronium Piperacillin when used concomitantly with vecuronium has been implicated in the …

8 USE IN SPECIFIC POPULATIONS Dosage in patients with renal impairment (creatinine clearance ≤40 mL/min) should be reduced based on the degree of renal impairment. ( 2.4 , 8.6 ) 8.1 Pregnancy Risk Summary Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. No fetal structural abnormalities were observed in rats or mice when piperacillin and tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area (mg/m 2 ). However, fetotoxicity in the presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area (mg/m 2 ) (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies in mice and rats, pregnant animals received intravenous doses of piperacillin and tazobactam up to 3000/750 mg/kg/day during the period of organogenesis. There was no evidence of teratogenicity up to the highest dose evaluated, which is 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, in mice and rats respectively, based on body-surface area (mg/m 2 ). Fetal body weights were reduced in rats at maternally toxic doses at or above 500/62.5 mg/kg/day, minimally representing 0.4 times the human dose of both piperacillin and tazobactam based on body-surface area (mg/m 2 ). A fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin and tazobactam prior to mating and through the end of gestation, reported a decrease in litter size in the presence of maternal toxicity at 640 mg/kg/day tazobactam (4 times the human dose of tazobactam based on body-surface area), and decreased litter size and an increase in fetuses with ossification delays and variations of ribs, concurrent with maternal toxicity at ≥640/160 mg/kg/day piperacillin and tazobactam (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area). Peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses ≥320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin and tazobactam at doses ≥640/160 mg/kg/day (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area) from gestation day 17 through lactation day 21. 8.2 Lactation Risk Summary Piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied. No information is available on the effects of piperacillin and tazobactam on the breast- fed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Piperacillin and Tazobactam for Injection and Sodium Chloride Injection and any potential adverse effects on the breast-fed child from Piperacillin and Tazobactam for Injection and Sodium Chloride Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection for intra-abdominal infections, and no …

12.1 Mechanism of Action Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is an antibacterial drug [see Microbiology (12.4) ].

11 DESCRIPTION Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is an injectable antibacterial combination product consisting of the semisynthetic antibacterial piperacillin sodium and the beta-lactamase inhibitor tazobactam sodium for intravenous administration. Piperacillin sodium is derived from D(-)-α-aminobenzyl-penicillin. The chemical name of piperacillin sodium is sodium (2 S ,5 R ,6 R )-6-[( R )-2-(4-ethyl-2,3-dioxo-1-piperazine-carboxamido)-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. The chemical formula is C 23 H 26 N 5 NaO 7 S and the molecular weight is 539.5. The chemical structure of piperacillin sodium is: Tazobactam sodium, a derivative of the penicillin nucleus, is a penicillanic acid sulfone. Its chemical name is sodium (2 S, 3 S, 5 R )-3-methyl-7-oxo-3-(1 H -1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate-4,4-dioxide. The chemical formula is C 10 H 11 N 4 NaO 5 S and the molecular weight is 322.3. The chemical structure of tazobactam sodium is: Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is supplied as a sterile powder for injection and a sterile solution in a single-dose DUPLEX ® Container with a strength of 2.25 g, 3.375 g, or 4.5 g in the following presentations: 2.25 g: contains 2 grams of piperacillin (equivalent to 2.085 g of piperacillin sodium), 0.25 g of tazobactam (equivalent to 0.269 g of tazobactam sodium), 0.5 mg of edetate sodium dihydrate (EDTA), and 100 mg of sodium citrate dihydrate in the powder chamber. The diluent chamber contains 225 mg of sodium chloride and 50 mL of water for injection. 3.375 g: contains 3 grams of piperacillin (equivalent to 3.127 g of piperacillin sodium) and 0.375 g of tazobactam (equivalent to 0.402 g of tazobactam sodium), 0.75 mg of EDTA, and 150 mg of sodium citrate dihydrate in the powder chamber. The diluent chamber contains 150 mg of sodium chloride and 50 mL of water for injection. 4.5 g: contains 4 grams of piperacillin (equivalent to 4.170 g of piperacillin sodium), 0.5 g of tazobactam (equivalent to 0.538 g of tazobactam sodium), 1 mg of EDTA, and 200 mg of sodium citrate dihydrate. The diluent chamber contains 450 mg of sodium chloride and 100 mL of water for injection. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection contains a total of 9.6 mEq (220 mg), 11.1 mEq (256 mg), and 19.1 mEq (440 mg) of sodium (Na+) per 2.25 g, 3.375 g, and 4.5 g product, respectively [see Warnings and Precautions (5.8) and Use in Specific Populations (8.5) ] . The reconstituted solution has a pH between 5.0 and 7.0. The osmolality of the reconstituted solution of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is approximately 318 mOsmol/kg for the 2.25 g strength, approximately 348 mOsmol/kg for the 3.375 g strength, and approximately 318 mOsmol/kg for the 4.5 g strength. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection Meets USP Monograph Organic Impurities Procedure 3. The DUPLEX ® Container is a flexible dual chamber container. After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is hyperosmotic and is intended for single intravenous use. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene copolymer that contains no plasticizers. Not made with natural rubber latex, PVC or Di(2-ethylhexyl)phthalate (DEHP). Chemical Structure illustration of piperacillin sodium Chemical structure illustration of tazobactam sodium

10 OVERDOSAGE There have been postmarketing reports of overdose with piperacillin and tazobactam. The majority of those events experienced, including nausea, vomiting, and diarrhea, have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or seizures if higher than recommended doses are given intravenously (particularly in the presence of renal failure) [see Warnings and Precautions (5.6) ]. Treatment should be supportive and symptomatic according to the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis. Following a single 3.375 g dose of piperacillin and tazobactam, the percentage of the piperacillin and tazobactam dose removed by hemodialysis was approximately 31% and 39%, respectively [see Clinical Pharmacology (12) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Piperacillin and Tazobactam for Injection USP and Sodium Chloride Injection USP is a white to off-white powder and a clear, colorless solution supplied in a single-dose DUPLEX ® Container (packaged 24 single-dose units per case) in the following strengths described in Table 8 below: Table 8: Strengths, Volume of Diluent, National Drug Code (NDC), Total Sodium for Piperacillin and Tazobactam for Injection and Sodium Chloride Injection Strength (piperacillin and tazobactam) Piperacillin Tazobactam Volume of Diluent NDC Total Sodium REF 2.25 g 2 g 0.25 g 50 mL of 0.45% Sodium Chloride 0264- 3446-11 9.6 mEq (220 mg) 3446-11 3.375 g 3 g 0.375 g 50 mL of 0.3% Sodium Chloride 0264- 3448-11 11.1 mEq (256 mg) 3448-11 4.5 g 4 g 0.5 g 100 mL of 0.45% Sodium Chloride 0264- 3450-22 19.1 mEq (440 mg) 3450-22 Prior to reconstitution, store Piperacillin and Tazobactam for Injection USP and Sodium Chloride Injection USP at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Do not remove the foil strip until ready to use to protect from light. After removal of the foil strip, product must be used within 7 days, but not beyond the labeled expiration date. Protect from light after removal of foil strip. Storage conditions for reconstituted Piperacillin and Tazobactam for Injection are described in another section of labeling [see Dosage and Administration (2.5) ]. Do not freeze.