Piperacillin and tazobactam

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 for Injection and Sodium Chloride Injection should be reduced based on the degree of renal impairment.

The recommended daily dosage of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1. [See table below.] 2.25 g every 6 hours Hemodialysis 0.75 g (0.67 g piperacillin and 0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days 2.25 g every 12 hours 2.25 g every 8 hours CAPD 2.25 g every 12 hours 2.25 g every 8 hours For patients on hemodialysis, the maximum dose is 2.25 g every 12 hours for all indications other than nosocomial pneumonia and 2.25 g every 8 hours for nosocomial pneumonia.

Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam for injection should be administered following each dialysis period on hemodialysis days. No additional dosage of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is necessary for CAPD patients.

Hepatic Impairment Dosage adjustment of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is not warranted in patients with hepatic cirrhosis [see Clinical Pharmacology ].

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.

Preparation and Administration of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection in the DUPLEX ® Container Important Administration Instructions Do not use in series connections. Such use would result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. Do not introduce additives into the DUPLEX ® Container. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

Piperacillin and Tazobactam for Injection and Sodium Chloride Injection should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and container and seals are intact.

Administer Piperacillin and Tazobactam for Injection and Sodium Chloride Injection intravenously over 30 minutes. This reconstituted solution is for intravenous use only. DUPLEX ® Container Storage To avoid inadvertent activation, the DUPLEX ® Container should remain in the folded position until activation is intended. Patient Labeling and Drug Powder/Diluent Inspection Apply patient-specific label on foil side of container.

Use care to avoid activation. Do not cover any portion of foil strip with patient label. Peel sticker halfway off and unfold DUPLEX ® Container (see Diagram 1 ). Visually inspect diluent chamber for particulate matter. Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel foil strip from drug chamber (see Diagram 2 ).

Protect from light after removal of foil strip. Note: If foil strip is removed, the container should be re-folded and the sticker reapplied until ready to activate. The product must then be used within 7 days at room temperature at 20°C to 25°C (68°F to 77°F), but not beyond the labeled expiration date. Reconstitution (Activation) Do not use directly after storage by refrigeration, allow the product to equilibrate to room temperature before patient use.

Unfold the DUPLEX ® Container and point the set port in a downward direction. Starting at the hanger tab end, fold the DUPLEX ® Container just below the diluent meniscus trapping all air above the fold. To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber (see Diagram 3 ).

Agitate the liquid-powder mixture until the drug powder is completely dissolved. Note: Following reconstitution (activation), the reconstituted product must be used within 24 hours if stored at room temperature at 20°C to 25°C (68°F to 77°F) or within 7 days if stored under refrigeration at 2°C to 8°C (36°F to 46°F). Administration Visually inspect the reconstituted solution for particulate matter.

Point the set port in a downwards direction. Starting at the hanger tab end, fold the DUPLEX ® Container just below the solution meniscus trapping all air above the fold. Squeeze the folded DUPLEX ® Container until the seal between reconstituted drug solution and set port opens, releasing liquid to set port (see Diagram 4 ).

Prior to attaching the intravenous set, check for minute leaks by squeezing container firmly. If leaks are found, discard container and solution as sterility may be compromised. Using aseptic technique, peel foil cover from the set port and attach sterile administration set (see Diagram 5 ). Refer to directions for use accompanying the administration set.

Discard unused portion. Compatible Intravenous Solutions for Co-administration via a Y-site 0.9% sodium chloride for injection Sterile water for injection (Maximum recommended volume per dose of sterile water for injection is 50 mL) Dextrose 5% Lactated Ringer's Solution Piperacillin and Tazobactam for Injection and Sodium Chloride Injection should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

Piperacillin and Tazobactam for Injection and Sodium Chloride Injection for Pediatric Patients Weighing up to 40 kg The volume of reconstituted solution required to deliver the dose of Piperacillin and Tazobactam is dependent on the weight of the pediatric patient [see Dosage and Administration ]. 1. Calculate patient dose as described in Table 2 above [see Dosage and Administration ]. 2.

Piperacillin and Tazobactam for Injection and Sodium Chloride Injection in the DUPLEX ® Container should be used only in patients who require the entire 2.25 g, 3.375 g, or 4.5 g dose and not any fraction thereof. Stability of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection Following Reconstitution Stability studies after reconstitution in the DUPLEX ® Containers, have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature at 20°C to 25°C (68°F to 77°F) and up to 7 days at refrigerated temperature at 2°C to 8°C (36°F to 46°F).

Piperacillin and Tazobactam for Injection and Sodium Chloride Injection contains no preservatives. Appropriate consideration of aseptic technique should be used. Diagram 1 Diagram 2 Diagram 3 Diagram 4 Diagram 5

Compatibility With Aminoglycosides Due to the in vitro inactivation of aminoglycosides by piperacillin, Piperacillin and Tazobactam for Injection and Sodium Chloride Injection 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 [see Drug Interactions ].

In circumstances where co-administration via Y-site is necessary, Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is compatible for simultaneous co-administration via Y-site infusion only with the following aminoglycosides under the following conditions: [See table below.] Gentamicin 2.25 g 3.375 g 4.5 g 50 mL 50 mL 100 mL 0.7 mg/mL to 3.32 mg/mL 0.9% sodium chloride or 5% dextrose Only the concentration and diluents for amikacin or gentamicin with the dosages of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection listed above have been established as compatible for co-administration via Y-site infusion.

Simultaneous co-administration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by Piperacillin and Tazobactam for Injection and Sodium Chloride Injection. Piperacillin and Tazobactam for Injection and Sodium Chloride Injection is not compatible with tobramycin for simultaneous co-administration via Y-site infusion.

Compatibility of Piperacillin and Tazobactam for Injection and Sodium Chloride Injection with other aminoglycosides has not been established.