Emblaveo (aztreonam/avibactam sodium)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Administer by IV infusion, after reconstitution and further dilution. See Full Prescribing Information for additional details on preparation and administration.

Recommended dosage is based on creatinine clearance (Clcr), calculated using the Cockcroft-Gault formula (see Table 1). Aztreonam/avibactam is a combination product in a fixed 3:1 ratio. A single loading dose is followed by maintenance doses beginning at the next dosing interval. The dosing interval is calculated from the start of one infusion to the start of the subsequent infusion.

Table 1: Recommended Dosage in Adults based on Estimated Creatinine Clearance (Clcr)

Estimated CLcr Loading Dose Maintenance Infusion Time Dosing (mL/min) Dose Interval Greater than Aztreonam/ Aztreonam/ 3 hours Every 6 hours 50 mL/min avibactam 2.67 avibactam 2 g g (aztreonam 2 (aztreonam 1.5 g and g and avibactam 0.67 avibactam 0.5 g) g) Greater than Aztreonam/avib Aztreonam/avib 3 hours Every 6 hours 30 to less actam 2.67 g actam 1 g than or equal (aztreonam 2 g (aztreonam to 50 mL/min and avibactam 0.75 g and 0.67 g) avibactam 0.25 g) Greater than Aztreonam/avib Aztreonam/avib 3 hours Every 8 hours 15 to less actam 1.8 g actam 0.9 g than or equal (aztreonam (aztreonam to 30 mL/min 1.35 g and 0.675 g and avibactam 0.45 avibactam g) 0.225 g) Less than or Aztreonam/avib Aztreonam and 3 hours Every 12 hours equal to 15 actam 1.33 g avibactam 0.9 mL/min, (aztreonam 1 g g (aztreonam including on and avibactam 0.675 g and hemodialysis 0.33 g) avibactam 0.225 g)

Both aztreonam and avibactam are hemodialyzable; thus, administer after hemodialysis on hemodialysis days.

For treatment of cIAI, administer metronidazole concurrently.

Recommended duration of treatment for cIAI is 5 to 14 days.

No dosing information is available for this tab.

No dosing information is available for this tab.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity to the components of aztreonam and avibactam.

There are no contraindication contraindications for this drug.

• 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

• 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)

The most common adverse reactions occurring at an incidence of greater than 5% were hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia.

There are no severe adverse reactions for this drug.

More Frequent

• Anemia
• Diarrhea
• Fever
• Hypokalemia

Less Frequent

• 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 or Very Rare

• Clostridioides difficile infection

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The safety and effectiveness of aztreonam and avibactam in pediatric patients less than 18 years of age have not been established.

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).