Consumer medicine information

1 Name of Medicine

Ceftolozane sulfate/tazobactam sodium.

2 Qualitative and Quantitative Composition

Each vial contains 1000 mg of ceftolozane (as ceftolozane sulfate) and 500 mg tazobactam (as tazobactam sodium).
Ceftolozane sulfate is a white to off white hygroscopic powder that is freely soluble in water and 0.05 M sodium perchlorate, insoluble in isopropyl alcohol, acetonitrile, dichloromethane and methyl-tert-butyl ether and slightly soluble in N-methylpyrrolidone. The pH of a 20 mg/mL (2%) aqueous solution is 1.92. The pKa is 9.3, 3.2, and 1.9. Ceftolozane sulfate is a single stereoisomer with the 6R, 7R configuration.
Tazobactam sodium is a white to off-white, hygroscopic powder, that is freely soluble in water and slightly soluble in ethanol and acetone. The pH of an aqueous solution of the drug substance is 5.0-7.0. The specific optical rotation is between +138.0° and 152.0°.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Zerbaxa (ceftolozane sulfate/tazobactam sodium) is a white to yellow powder for solution.
Zerbaxa (ceftolozane/tazobactam) solutions range from clear, colourless solutions to solutions that are clear and slightly yellow.

4 Clinical Particulars

4.9 Overdose

In the event of overdose, Zerbaxa (ceftolozane/tazobactam) should be discontinued and general supportive treatment should be given. Zerbaxa (ceftolozane/tazobactam) can be removed by haemodialysis. Approximately 66% of ceftolozane, 56% of tazobactam, and 51% of the M1 metabolite of tazobactam were removed by approximately 3-4 hour period of haemodialysis. However, no information is available on the use of haemodialysis to treat overdosage.
The highest single dose of Zerbaxa (ceftolozane/tazobactam) received in clinical trials was 3.0 g/1.5 g of ceftolozane/tazobactam. At this dosage, no adverse pharmacological effects have been observed.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Zerbaxa (ceftolozane/tazobactam) was not genotoxic in vivo. Zerbaxa (ceftolozane/tazobactam) was negative for genotoxicity in an in vitro mouse lymphoma assay and an in vivo rat bone-marrow micronucleus assay. In an in vitro chromosomal aberration assay in Chinese hamster ovary cells, Zerbaxa (ceftolozane/tazobactam) was positive for structural aberrations, but only at highly toxic concentrations.
Ceftolozane was negative for genotoxicity in an in vitro microbial mutagenicity (Ames) assay, an in vitro chromosomal aberration assay in Chinese hamster lung fibroblast cells, an in vitro mouse lymphoma assay, an in vitro HPRT point mutation assay in Chinese hamster ovary cells, an in vivo mouse micronucleus assay, and an in vivo unscheduled DNA synthesis (UDS) assay.
Tazobactam was negative for genotoxicity in an in vitro microbial mutagenicity (Ames) assay, an in vitro chromosomal aberration assay in Chinese hamster lung cells, a HPRT point mutation assay in Chinese hamster ovary cells, an in vivo rat chromosomal aberration assay, an in vivo mouse bone-marrow micronucleus assay, and a UDS assay. Tazobactam was positive for genotoxicity in an in vitro mouse lymphoma assay at ≥ 3000 microgram/mL.
Carcinogenicity. Carcinogenicity studies with ceftolozane, tazobactam, or Zerbaxa (ceftolozane/tazobactam) have not been conducted.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Ceftolozane sulfate. Ceftolozane sulfate is a semisynthetic antibiotic and is described chemically as 1H-pyrazolium, 5-amino-4[[[(2-aminoethyl)amino]carbonyl] amino]-2-[[(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(1carboxy-1-methylethoxy)imino] acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0] oct-2-en-3yl] methyl]-1-methyl-,sulfate (1:1).
The empirical formula of ceftolozane sulfate is C₂₃H₃₁N₁₂O₈S₂⁺.HSO₄^- with a molecular weight of 764.77.
Tazobactam sodium. Tazobactam sodium is described chemically as Sodium(2S,3S,5R)-3-methyl-7-oxy-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo-[3.2.0] heptane-2- carboxylate-4,4-dioxide.
The empirical formula of tazobactam sodium is C₁₀H₁₁N₄NaO₅S with a molecular weight of 322.28.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSCFTSUL.gif https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSTAZSOD.gif CAS number. Ceftolozane sulfate: 936111-69-2.
Tazobactam sodium: 89785-84-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (S4).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/ZERBAXST.gif