Avibactam and Ceftazidime

AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of the following infections caused by designated susceptible Gram-negative microorganisms in adult and pediatric patients (at least 31 weeks gestational age): Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole. Complicated Urinary Tract Infections (cUTI), including Pyelonephritis. Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP).

AVYCAZ is an antibacterial drug.

Dosage of AVYCAZ in Adult Patients with Creatinine Clearance (CrCl) greater than 50 mL/min. Infection Dose Frequency Infusion Time cIAI *, cUTI including Pyelonephritis, and HABP/VABP AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) Every 8 hours 2 hours * Used in conjunction with metronidazole 0.5 g intravenously every 8 hours in adult cIAI patients Dosage of AVYCAZ in Pediatric Patients aged 2 years to less than 18 years with Estimated Glomerular Filtration Rate (eGFR) greater than 50 mL/min/1.73 m 2 and in Pediatric Patients less than 2 years of age without Renal Impairment.

AVYCAZ is contraindicated in patients with known serious hypersensitivity to the components of AVYCAZ (ceftazidime and avibactam), avibactam containing products, or other members of the cephalosporin class.

Decreased Clinical Response in A dult cIAI P atients with B aseline CrC l of 30 to L ess T han or E qual to 50 mL/ min: Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage of AVYCAZ accordingly. Hypersensitivity R eactions: Includes anaphylaxis and serious skin reactions. Cross sensitivity may occur in patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue AVYCAZ. Clostrid io i des difficile -associated D iarrhea (CDAD): CDAD has been reported with nearly all systemic antibacterial agents, including AVYCAZ. Evaluate if diarrhea occurs. C entral Nervous System Reactions: Seizures and other neurologic events may occur, especially in patients with renal impairment. Adjust dose in patients with renal impairment.

The following adverse reactions are discussed in greater detail in the Warnings and Precautions section: Hypersensitivity Reactions Clostridi oid e s difficile -Associated Diarrhea Central Nervous System Reactions Adult Patients: The most common adverse reactions in cIAI (≥ 5%, when used with metronidazole) patients are diarrhea, nausea and vomiting. The most common adverse reactions (3%) in cUTI patients are diarrhea and nausea. The most common adverse reactions (≥ 5%) in HABP/VABP patients were diarrhea and vomiting. Pediatric Patients (aged 3 months to less than 18 years): The most common adverse reactions (≥ 3%) in pediatric patients aged 3 months and older were vomiting, diarrhea, rash, and infusion site phlebitis.

Probenecid In vitro, avibactam is a substrate of OAT1 and OAT3 transporters which might contribute to the active uptake from the blood compartment, and thereby its excretion. As a potent OAT inhibitor, probenecid inhibits OAT uptake of avibactam by 56% to 70% in vitro and, therefore, has the potential to decrease the elimination of avibactam when co-administered. Because a clinical interaction study of AVYCAZ or avibactam alone with probenecid has not been conducted, co-administration of AVYCAZ with probenecid is not recommended.

Store in carton until time of use. Storage conditions for constituted and diluted solutions of AVYCAZ for injection are described in another section of labeling.