AVYCAZ- ceftazidime, avibactam powder, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CEFTAZIDIME (UNII: 9M416Z9QNR) (CEFTAZIDIME ANHYDROUS - UNII:DZR1ENT301), AVIBACTAM SODIUM (UNII: 9V824P8TAI) (AVIBACTAM - UNII:7352665165)

Available from:

Allergan, Inc.

INN (International Name):

ceftazidime

Composition:

ceftazidime anhydrous 2 g

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

AVYCAZ (ceftazidime and avibactam) in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli ,   Klebsiella pneumoniae ,   Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa . AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli ,   Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis , and Pseudomonas aeruginosa . AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae . To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 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 [see Warnings and Precautions ( 5.2)] . Risk Summary There are no adequate and well-controlled studies of AVYCAZ, ceftazidime, or avibactam in pregnant women. Neither ceftazidime nor avibactam were teratogenic in rats at doses 40 and 9 times the recommended human clinical dose. In the rabbit, at twice the exposure as seen at the human clinical dose, there were no effects on embryofetal development with avibactam. The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies within the general population. Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed. Data Animal Data Ceftazidime Reproduction studies have been performed in mice and rats at doses up to 40 times the human dose and showed no evidence of harm to the fetus due to ceftazidime. Avibactam Avibactam was not teratogenic in rats or rabbits. In the rat, intravenous studies with 0, 250, 500 and 1000 mg/kg/day avibactam during gestation days 6-17 showed no embryofetal toxicity at doses up to 1000 mg/kg/day, approximately 9 times the human dose based on exposure (AUC). In a rat pre- and post-natal study at up to 825 mg/kg/day intravenously (11 times the human exposure based on AUC), there were no effects on pup growth and viability. A dose-related increase in the incidence of renal pelvic and ureter dilatation was observed in female weaning pups that was not associated with pathological changes to renal parenchyma or renal function, with renal pelvic dilatation persisting after female weaning pups became adults. Rabbits administered intravenous avibactam on gestation days 6-19 at 0, 100, 300 and 1000 mg/kg/day showed no effects on embryofetal development at a dose of 100 mg/kg, twice the human exposure (AUC). At higher doses, increased post-implantation loss, lower mean fetal weights, delayed ossification of several bones and other anomalies were observed. Risk Summary Ceftazidime is excreted in human milk in low concentrations. It is not known whether avibactam is excreted into human milk, although avibactam was shown to be excreted in the milk of rats. No information is available on the effects of ceftazidime and avibactam on the breast-fed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AVYCAZ and any potential adverse effects on the breastfed child from AVYCAZ or from the underlying maternal conditions. Data In a rat pre- and post-natal study at doses up to 825 mg/kg/day intravenously (11 times the human exposure based on AUC), the exposure to avibactam was minimal in the pups in comparison to the dams. Exposure to avibactam was observed in both pups and milk on PND 7. The safety and effectiveness of AVYCAZ in the treatment of cUTI, cIAI, and HABP/VABP have been established in pediatric patients at least 31 weeks gestational age and older. Use of AVYCAZ is supported by evidence from adequate and well-controlled studies of AVYCAZ in adults with cUTI, cIAI, and HABP/VABP and additional pharmacokinetic and safety data from pediatric trials [see Clinical Pharmacology ( 12.3), Clinical Studies ( 14.1 and  14.2)] . The safety profile of AVYCAZ in pediatric patients was similar to adults with cIAI, cUTI, and HABP/VABP treated with AVYCAZ [see Adverse Reactions ( 6.1) ] . The safety and effectiveness of AVYCAZ in the treatment of cUTI, cIAI, and HABP/VABP have not been established in pediatric patients less than 31 weeks gestational age. Of the 1809 patients treated with AVYCAZ in the Phase 2 and Phase 3 clinical trials 621 (34.5%) were 65 years of age and older, including 302 (16.7 %) patients 75 years of age and older. In the pooled Phase 2 and Phase 3 cIAI AVYCAZ clinical trials, 20% (126/630) of patients treated with AVYCAZ were 65 years of age and older, including 49 (7.8%) patients 75 years of age and older. The incidence of adverse reactions in both treatment groups was higher in older patients (≥ 65 years of age) and similar in both treatment groups; clinical cure rates for patients 65 years of age or older were 73.0% (73/100) in the AVYCAZ plus metronidazole arm and 78.6% (77/98) in the meropenem arm. In the Phase 3 cUTI trial, 30.7% (157/511) of patients treated with AVYCAZ were 65 years of age or older, including 78 (15.3%) patients 75 years of age or older. The incidence of adverse reactions in both treatment groups was lower in older patients (≥ 65 years of age) and similar between treatment groups. Among patients 65 years of age or older in the Phase 3 cUTI trial, 66.1% (82/124) of patients treated with AVYCAZ had symptomatic resolution at Day 5 compared with 56.6% (77/136) of patients treated with doripenem. The combined response (microbiological cure and symptomatic response) observed at the test-of-cure (TOC) visit for patients 65 years of age or older were 58.1% (72/124) in the AVYCAZ arm and 58.8% (80/136) in the doripenem arm. In the Phase 3 HABP/VABP trial, 54.1% (236/436) of patients treated with AVYCAZ were 65 years of age or older, including 129 (29.6%) patients 75 years of age or older. The incidence of adverse reactions in patients ≥ 65 years of age was similar to patients < 65 years of age. The 28-day all-cause mortality was similar between treatment groups for patients 65 years of age or older (12.7% [29/229] for patients in the AVYCAZ arm and 11.3% [26/230] for patients in the meropenem arm). Ceftazidime and avibactam are known to be substantially excreted by the kidney; therefore, the risk of adverse reactions to ceftazidime and avibactam may be greater in patients with decreased renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. Healthy elderly subjects had 17% greater exposure relative to healthy young subjects when administered the same single dose of avibactam, which may have been related to decreased renal function in the elderly subjects. Dosage adjustment for elderly patients should be based on renal function [ see Dosage and Administration ( 2.2) and Clinical Pharmacology ( 12.3) ]. Dosage adjustment is required in adult patients with moderately or severely impaired renal function (CrCl 50 mL/min or less). For patients with changing renal function, CrCl should be monitored at least daily, particularly early in treatment, and dosage of AVYCAZ adjusted accordingly. Both ceftazidime and avibactam are hemodialyzable; thus, AVYCAZ should be administered after hemodialysis on hemodialysis days [ see Dosage and Administration ( 2.2) and Clinical Pharmacology ( 12.3) ] . Dosage adjustment is also required in pediatric patients with renal impairment from 2 years to less than 18 years of age with eGFR 50 mL/min/1.73 m2 or less. There is insufficient information to recommend a dosing regimen for pediatric patients younger than 2 years of age with renal impairment [see Dosage and Administration ( 2.3) and Clinical Pharmacology ( 12.3)] .

Product summary:

AVYCAZ 2.5 grams (ceftazidime and avibactam) for injection is supplied in single-dose, clear glass vial containing: ceftazidime 2 grams (equivalent to 2.635 grams of ceftazidime pentahydrate/sodium carbonate) and avibactam 0.5 grams (equivalent to 0.551 grams of avibactam sodium). Vials are supplied as individual vial (NDC#   0456-2700-01) and in cartons containing 10 vials (NDC# 0456-2700-10). AVYCAZ vials should be stored at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Protect from light. 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 [see Dosage and Administration ( 2.4, 2.6)] .

Authorization status:

New Drug Application

Summary of Product characteristics

AVYCAZ- CEFTAZIDIME, AVIBACTAM POWDER, FOR SOLUTION
ALLERGAN, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
AVYCAZ SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR AVYCAZ.
AVYCAZ (CEFTAZIDIME AND AVIBACTAM) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2015
RECENT MAJOR CHANGES
Indications and Usage (1.1_, _1.2_,_ 1.3)1/2024
Dosage and Administration
(2.2)
1/2024
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 AND IN
PEDIATRIC PATIENTS
LESS THAN 2 YEARS OF AGE WITHOUT RENAL IMPAIRMENT (2.2)
Infection
Age Range
Dose
Infusion
Time/Frequency
cIAI , cUTI
including
Pyelonephritis,
HABP/VABP
2 years to less
than 18 years
AVYCAZ 62.5 mg/kg to a maximum of 2.5 grams
(ceftazidime 50 mg/kg and avibactam 12.5 mg/kg to a
maximum dose of ceftazidime 2 grams and
avibactam 0.5 grams)
2 hours/
Every 8 hours
6 months to less
than 2 years
AVYCAZ 62.5 mg/kg (ceftazidime 50 mg/kg and
avibactam 12.5 mg/kg)
3 months to less
than 6 months
AVYCAZ 50 mg/kg (ceftazidime 40 mg/kg and
avibactam 10 mg/kg)
Greater than 28
days to less than
3 months
AVYCAZ 37.5 mg/kg
(ceftazidime 30 mg/kg and avibactam 7.5 mg/kg)
Less than or equal
to 28 days with
GA 31 weeks and
older
AVYCAZ 25 mg/kg (ceftazidime 20 mg/kg and
avibactam 5 mg/kg)
INDICATIONS AND USAGE
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 (1.1)
Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
(1.2)
Hospital-acquired Bacterial Pneumonia and Ventilator-associated
Bacterial Pneumonia (HABP/VABP)
(1.3)
To reduce the development of drug-resistant bac