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The Food and Drug Administration (FDA) has approved the supplemental New Drug Applications (sNDAs) for Zerbaxa® (ceftolozane and tazobactam) to include treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI), including pyelonephritis, in pediatric patients (birth to less than 18 years old). Previously, the treatment was only approved for adults.
Zerbaxa is a combination of ceftolozane, a cephalosporin antibacterial, and tazobactam, a beta-lactamase inhibitor. Pediatric approval was based on data from randomized, active comparator-controlled, double-blind studies (cIAI; ClinicalTrials.gov Identifier: NCT03217136 and cUTI; ClinicalTrials.gov Identifier: NCT03230838). The primary endpoint for both trials was the safety and tolerability of Zerbaxa.
Findings showed that the safety profile in pediatric patients was similar to adults with cIAI and cUTI. The most common adverse reactions reported in pediatric patients were thrombocytosis, diarrhea, pyrexia, leukopenia, abdominal pain, vomiting, increased aspartate aminotransferase, and anemia.
In the pediatric cIAI trial, 80% (n=56/70) of patients in the modified intent-to-treat (MITT) population treated with Zerbaxa plus metronidazole achieved clinical response (defined as complete resolution or marked improvement in signs and symptoms of the cIAI or return to pre-infection signs and symptoms such that no further antibiotic therapy or surgical or drainage procedure was required at the test-of-cure [TOC] visit) compared with 100% (n=21/21) of patients treated with meropenem. In the clinically evaluable population, 89.7% (n=52/58) of patients treated with Zerbaxa plus metronidazole achieved clinical response vs 100% (n=19/19) of those treated with meropenem.
In the pediatric cUTI trial, 88.7% (n=63/71) of patients in the microbiologic MITT population treated with Zerbaxa achieved clinical response (defined as complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy was required) compared with 95.8% (n=23/24) of patients treated with meropenem. Moreover, 84.5% (n=60/71) of patients treated with Zerbaxa had a favorable microbiologic response (defined as eradication of baseline uropathogens from the urine culture at the TOC visit) vs 87.5% (n=21/24) of those treated with meropenem.
Zerbaxa is also indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years of age and older. Safety and effectiveness in pediatric patients for this indication have not been established.
References
- US Food and Drug Administration. NDA 206829/S-011 NDA 206829/S-012 supplement approval letter: fulfillment of postmarketing requirement. Accessed April 25, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/206829Orig1s011,%20s012ltr.pdf
- Zerbaxa. Package insert. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; 2022. Accessed April 25, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206829s011s012lbl.pdf
