IMPORTANT SAFETY INFORMATION
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.
WARNINGS AND PRECAUTIONS
In a Phase 3 cIAI trial in adult patients, clinical cure rates were lower in a subgroup of patients with
baseline creatinine clearance (CrCl) of 30 to less than or equal to 50 mL/min compared to those with
CrCl greater than 50 mL/min. The reduction in clinical cure rates was more marked in patients treated
with AVYCAZ plus metronidazole compared to meropenem-treated patients. Within this subgroup, patients
treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with
CrCl of 30 to less than or equal to 50 mL/min. Clinical cure rate in patients with normal renal
function/mild renal impairment (CrCl greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus
metronidazole vs 86% (321/373) with meropenem, and clinical cure rate in patients with moderate
renal impairment (CrCl 30 to less than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus
metronidazole vs 74% (26/35) with meropenem. The decreased clinical response was not observed
for patients with moderate renal impairment at baseline (CrCl 30 to less than or equal to 50 mL/min)
in the Phase 3 cUTI trials or the Phase 3 HABP/VABP trial. Monitor CrCl at least daily in adult and
pediatric patients with changing renal function and adjust the dosage of AVYCAZ accordingly.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions
have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with
AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins,
penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a
penicillin or other beta-lactam-allergic patient because cross sensitivity among beta-lactam
antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs.
Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic
antibacterial drugs, including AVYCAZ, and may range in severity from mild diarrhea to fatal colitis.
Careful medical history is necessary because CDAD has been reported to occur more than 2 months after
the administration of antibacterial drugs. If CDAD is suspected or confirmed, antibacterials not
directed against C. difficile should be discontinued, if possible.
Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular
excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly
in the setting of renal impairment. Adjust dosing based on CrCl.
Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection is
unlikely to provide benefit to the patient and increases the risk of the development of
Adult cIAI, cUTI and HABP/VABP Patients:
The most common adverse reactions in adult patients with cIAI (≥ 5% when used with metronidazole)
were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in adult
patients with cUTI (3%) were diarrhea and nausea. The most common adverse reactions in adult
patients with HABP/VABP (≥ 5%) were diarrhea (15%) and vomiting (6%).
Pediatric cIAI and cUTI Patients:
The most common adverse reactions in pediatric patients with
cIAI and cUTI (>3%) were vomiting, diarrhea, rash, and infusion site phlebitis.
Please also see full Prescribing Information.