EMBLAVEO (aztreonam/avibactam sodium)

There are 0 contraindications.

There are 5 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Clostridioides difficile infection

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Child-pugh class A hepatic impairment
Child-pugh class B hepatic impairment
Child-pugh class C hepatic impairment
Disease of liver
Kidney disease with likely reduction in glomerular filtration rate (GFr)

There are 0 severe adverse reactions.

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Anemia Diarrhea Fever Hypokalemia	Abnormal hepatic function tests Acute abdominal pain Altered mental status Constipation Dizziness Eosinophilia Erythema Flushing General weakness Headache disorder Hypersensitivity drug reaction Hypotension Insomnia Leukocytosis Loss of taste Nausea Phlebitis Skin inflammation Skin rash Thrombocytopenic disorder Thrombocytosis Vomiting

Rare/Very Rare
Clostridioides difficile infection

There are no data on the effects of aztreonam/avibactam use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Available data from case reports over several decades with aztreonam and over approximately a decade with avibactam have not identified a drug-associated risk of major birth defects, miscarriage or other maternal or fetal outcomes. Developmental toxicity studies in pregnant rats and rabbits with daily doses of aztreonam revealed no evidence of embryotoxicity, fetotoxicity, or fetal malformations at doses 2.7-

and 3.6-fold greater, respectively, than the maximum recommended human dose (MRHD) for adults of 6.5 g per day.

In a peri/postnatal development (PPND) study in rats, no aztreonam-induced changes in any maternal, fetal, or neonatal parameters were observed at a dose 2.7-fold greater than the MRHD. Avibactam administered to pregnant rats was not associated with fetal malformations at doses 6 times the MRHD of 2.17

g per day. In pregnant rabbits, avibactam administered in doses greater than or equal to 5 times the MRHD was associated with increased post-implantation loss, lower mean fetal weights, delayed ossification of several bones and other anomalies. In a rat PPND study, there were no effects on pup growth and viability at doses up to 8 times the avibactam MRHD.

A dose-related increase in the incidence of renal pelvic and ureter dilatation was observed in female weaning pups with renal pelvic dilatation persisting into adulthood. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Aztreonam is present in human milk at concentrations that are less than 1% of those determined in simultaneously obtained maternal serum. There are no data on the presence of avibactam in human milk. Avibactam is present in the milk of rats.

When a drug is present in animal milk, it is likely that the drug will be present in human milk. There are no data on the effects of aztreonam or avibactam on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for aztreonam/avibactam and any potential adverse effects on the breast-fed infant from the combination drug or from the underlying maternal condition.

In the clinical development program for aztreonam/avibactam, there were 103 patients in the aztreonam/avibactam treatment arm who were 65 years of age and older. Of these patients, 60 (58%) were between 65-74 years of age and 43 (42%) patients were 75 years of age and older. In comparison, there were 202 patients in the aztreonam/avibactam treatment arm less than 65 years of age.

Clinical studies of aztreonam/avibactam did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Aztreonam and avibactam are known to be substantially excreted by the kidney, and the risk of adverse reactions to aztreonam/avibactam may be greater in patients with impaired 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. No dosage adjustment is required in elderly patients based on age; the dose should be selected based on renal function).