Indications and Usage
Complicated Intra-Abdominal Infections (cIAI)
AVYCAZ, in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI)
caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis,
Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa in patients 18 years or older.
Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
AVYCAZ is indicated for the treatment of complicated urinary tract infections (cUTI) including
pyelonephritis caused by the following susceptible microorganisms:
Proteus spp., and
in patients 18 years or older.
In the treatment of cUTI, as only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use
in patients with cUTI who have limited or no alternative treatment options.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs,
AVYCAZ should be used to treat only indicated infections that are proven or strongly suspected to be caused by susceptible bacteria.
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, 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. Clinical cure rates 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 rates 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. 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. Monitor CrCl at least daily in 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, 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 creatinine clearance.
- 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 drug-resistant bacteria.
The most common adverse reactions in cIAI (incidence of ≥5% when used with metronidazole) were diarrhea (8%), nausea (7%),
and vomiting (5%). In cUTI, the most common adverse reactions (incidence of ≥10%) were constipation (10%) and anxiety (10%).
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