The fixed combination of ceftolozane sulfate-tazobactam sodium is available as a lyophilized powder for injection in single-use (preservative-free) vials containing 1.5 g (ceftolozane 1 g as the sulfate plus tazobactam 0.5 g as the sodium salt).2958 Each vial also contains sodium chloride 487 mg, citric acid 21 mg, and L-arginine approximately 600 mg.2958
Reconstitute each 1.5-g vial with 10 mL of sterile water for injection or sodium chloride 0.9% and gently shake to dissolve.2958 The reconstituted solution is not suitable for direct injection.2958
The manufacturer’s instructions for preparing various dosages of ceftolozane-tazobactam from the reconstituted solution are as follows:2958
For a 3-g dose (ceftolozane 2 g plus tazobactam 1 g), withdraw the entire contents of 2 vials (i.e., approximately 11.4 mL per vial).
For a 2.25-g dose (ceftolozane 1.5 g plus tazobactam 0.75 g), withdraw the entire contents of 1 vial (i.e., approximately 11.4 mL) and 5.7 mL from a second vial.
For a 1.5-g dose (ceftolozane 1 g plus tazobactam 0.5 g), withdraw the entire contents of 1 vial (i.e., approximately 11.4 mL).
For a 750-mg dose (ceftolozane 500 mg plus tazobactam 250 mg), withdraw 5.7 mL.
For a 450-mg dose (ceftolozane 300 mg plus tazobactam 150 mg), withdraw 3.5 mL.
For a 375-mg dose (ceftolozane 250 mg plus tazobactam 125 mg), withdraw 2.9 mL.
For a 150-mg dose (ceftolozane 100 mg plus tazobactam 50 mg), withdraw 1.2 mL.
All doses should be added to an infusion bag containing 100 mL of a compatible diluent.
Trade Name(s)
Zerbaxa
Ceftolozane sulfate-tazobactam sodium is administered by intravenous infusion over 1 hour after dilution in an infusion bag containing 100 mL of sodium chloride 0.9% or dextrose 5%.2958
Intact vials of ceftolozane sulfate-tazobactam sodium should be stored under refrigeration at 2 to 8°C and protected from light.2958 Ceftolozane sulfate-tazobactam sodium is a white to yellow lyophilized powder that forms a clear, colorless to slightly yellow solution for infusion; variations in color within this range do not affect the potency of the product.2958 The drug reconstituted as instructed with sterile water for injection or sodium chloride 0.9% may be stored for 1 hour prior to dilution.2958 Following dilution in sodium chloride 0.9% or dextrose 5%, the drug is stable for 24 hours when stored at room temperature or 7 days when stored under refrigeration at 2 to 8°C.2958 Neither the reconstituted nor the diluted solutions should be frozen.2958
Elastomeric Reservoir Pumps
Ceftolozane sulfate-tazobactam sodium (Merck Sharp & Dohme) in sodium chloride 0.9% at concentrations of 5 mg/mL (ceftolozane 3.33 mg/mL plus tazobactam 1.67 mg/mL) or 20 mg/mL (ceftolozane 13.33 mg/mL plus tazobactam 6.67 mg/mL) was prepared in FOLFusor (Baxter) and Easypump II (B Braun) elastomeric reservoir pumps and stored refrigerated at 2 to 8°C for 8 days followed by exposure to 32°C to simulate outpatient administration conditions.4023 After 8 days of refrigerated storage followed by 12 hours at 32°C, both concentrations of solutions in both pumps were physically stable (i.e., no change in appearance, pH, or particulate matter) with less than 5% loss of either component.4023 Although presence of particulate matter and pH were not tested after 12 hours at 32°C, losses of either component were less than 10% at 18 hours with ceftolozane losses exceeding 22% in 110 hours at 32°C.4023
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Peritoneal Dialysis Solutions
The fixed combination of ceftolozane sulfate-tazobactam sodium (Merck Sharpe & Dohme) was evaluated for stability in Dianeal with dextrose 1.5% (Baxter), Dianeal with dextrose 2.5% (Baxter), Dianeal with dextrose 4.25% (Baxter), and Extraneal with icodextrin 7.5% (Baxter) at ceftolozane and tazobactam concentrations of 20 and 10 mg/L, respectively, with bags stored at 25, 4, and 37°C.3565 The fixed combination also was evaluated for stability in 2-compartment pH-neutral Balance with dextrose 1.3% (Fresenius), pH-neutral Balance with dextrose 2.3% (Fresenius), Physioneal with 1.36% dextrose (Baxter), Physioneal with 2.27% dextrose (Fresenius), and Physioneal with 3.86% dextrose (Fresenius).3565 Bags of 2-compartment pH-neutral Balance contained ceftolozane and tazobactam at concentrations of 40 and 20 mg/L, respectively, in the non-dextrose compartment for storage at 25 and 4°C; for storage at 37°C, the 2 compartments were combined immediately prior to storage for final ceftolozane and tazobactam concentrations of 20 and 10 mg/L, respectively.3565 Bags of 2-compartment Physioneal contained ceftolozane and tazobactam at concentrations of 55.1 and 27.5 mg/L, respectively, in the dextrose compartment for storage at 25 and 4°C; for storage at 37°C, the 2 compartments were combined immediately prior to storage for final ceftolozane and tazobactam concentrations of 20 and 10 mg/L, respectively.3565 No color change or particle formation was noted on visual assessment and no meaningful pH changes occurred.3565 In all solutions, losses of both drugs were less than 3% in 6 hours at 25°C followed by 7 days at 4°C and an additional 12 hours at 37°C.3565
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