Avibactam

EMBLAVEO is a combination of aztreonam, a monobactam antibacterial, and avibactam, a beta-lactamase inhibitor, that when used in combination with metronidazole, is indicated in patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI) including those caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens . Approval of this indication is based on limited clinical safety and efficacy data for EMBLAVEO. …

• Recommended Dosage
• In Adults based on Estimated Creatinine Clearance (C Lcr ) Estimated C Lcr (mL/min) a Dose b Infusion Time Dosing Interval c Loading Maintenance Greater than 50 mL/min EMBLAVEO 2.67 g (aztreonam 2 grams and avibactam 0.67 grams) EMBLAVEO 2 g (aztreonam 1.5 grams and avibactam 0.5 grams) 3 hours Every 6 hours Greater than 30 to less than or equal to 50 mL/min EMBLAVEO 2.67 g (aztreonam 2 grams and avibactam 0.67 grams) EMBLAVEO 1 g (aztreonam 0.75 grams and avibactam 0.25 grams) 3 hours Every 6 hours Greater than 15 to less than or equal to 30 mL/min EMBLAVEO 1.8 g (aztreonam 1.35 grams and avibactam 0.45 grams) EMBLAVEO 0.9 g (aztreonam 0.675 grams and avibactam 0.225 grams) 3 hours Every 8 hours Less than or equal to 15 mL/min, including on hemodialysis d EMBLAVEO 1.33 g (aztreonam 1 gram and avibactam 0.33 grams) EMBLAVEO 0.9 g (aztreonam 0.675 grams and avibactam 0.225 grams) 3 hours Every 12 hours a Calculated using the Cockcroft-Gault formula. b 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. c Dosing interval is calculated from the start of one infusion to the start of the subsequent infusion. d Both aztreonam and avibactam are removed by hemodialysis; thus, administer EMBLAVEO after hemodialysis, on hemodialysis days
• For treatment of cIAI, administer metronidazole concurrently
• Recommended duration of treatment for cIAI: 5 to 14 days. …

EMBLAVEO (aztreonam and avibactam) for injection is supplied as a white to slightly yellow sterile lyophilized powder for reconstitution in a single-dose, sterile, clear glass vial containing: 2 g aztreonam and avibactam (1.5 grams aztreonam and 0.5 grams avibactam (equivalent to 0.542 grams of avibactam sodium)). …

• The safety and effectiveness of EMBLAVEO
• In pediatric patients less than 18 years of age have not been established

In Trials 1, 2, and 3, there were 103 patients in the EMBLAVEO treatment arm 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 EMBLAVEO treatment arm less than 65 years of age. …

• Serious Allergic Reactions Advise patients, their families, or caregivers that allergic reactions, including serious allergic reactions, could occur that require immediate treatment
• Ask them about any previous hypersensitivity reactions to EMBLAVEO, other beta-lactams, or other allergens [see Warnings and Precautions ]
• Serious Skin Reactions Advise patients about the signs and symptoms of serious skin manifestations such as sudden onset of a severe rash or blistering or peeling skin, possibly accompanied by a high fever or joint pain (these may be signs of more serious medical conditions such as toxic epidermal necrolysis) [see Warnings and Precautions ] . …

• EMBLAVEO is contraindicated in patients with known hypersensitivity to the components of EMBLAVEO (aztreonam and avibactam) [see Warnings and Precautions ]
• Known hypersensitivity to the components of EMBLAVEO (aztreonam and avibactam)

7.1 OAT 1 and 3 Transport Inhibitors Concomitant use of organic anion transporter (OAT) 1 and OAT 3 transporter inhibitors (e.g., probenecid) with EMBLAVEO is not recommended. There is insufficient information to characterize the effect of concomitant use of OAT 1/3 transport inhibitors with EMBLAVEO [see Clinical Pharmacology ( 12.3 )].

Hypersensitivity Reactions : Hypersensitivity reactions were noted in patients treated with EMBLAVEO including rash, flushing, and bronchospasm. In case of hypersensitivity reactions, immediately discontinue EMBLAVEO and initiate appropriate medications and/or supportive care. ( 5.1 ) Serious Skin Disorders: Cases of toxic epidermal necrolysis have been reported in association with aztreonam (a component of EMBLAVEO) in patients undergoing bone marrow transplant with multiple risk factors. Discontinue EMBLAVEO if serious skin reaction occurs. ( 5.2 ) Hepatic Adverse Reactions: Elevations in hepatic transaminases have been observed during treatment with EMBLAVEO. …

The following adverse reactions are discussed in greater detail in the Warnings and Precautions section: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Serious Skin Disorders [see Warnings and Precautions ( 5.2 )] Hepatic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Clostridioides Difficile -Associated Diarrhea [see Warnings and Precautions ( 5.4 )] The most common adverse reactions occurring at an incidence of greater than 5% were hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary There are no data on the effects of EMBLAVEO 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. …

There is no information on the clinical signs and symptoms associated with an overdose of EMBLAVEO. Aztreonam and avibactam can be partially removed by hemodialysis [see Clinical Pharmacology ( 12.3 )] . No clinical information is available on the use of hemodialysis to treat EMBLAVEO overdosage.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.