EMBLAVEO Powder for solution for infusion Ref.[110084] Active ingredients: Avibactam Aztreonam Aztreonam and Avibactam

It is recommended that Emblaveo should be used to treat infections due to aerobic Gram-negative organisms in adult patients with limited treatment options only after consultation with a physician with appropriate experience in the management of infectious diseases.

Posology

Dose in adults with estimated creatinine clearance (CrCL) >50 mL/min

Table 1 shows the recommended intravenous dose for patients with a creatinine clearance (CrCL) >50 mL/min. A single loading dose is followed by maintenance doses beginning at the next dosing interval.

Table 1. Recommended intravenous dose by type of infection in adult patients with CrCL^a >50 mL/min:

^a Calculated using the Cockcroft-Gault formula.
^b To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process.

Special populations

Elderly

No dosage adjustment is required in elderly patients based on age (see section 5.2).

Renal impairment

No dosage adjustment is required in patients with mild renal impairment (estimated CrCL >50 to ≤80 mL/min).

Table 2 shows the recommended dose adjustments for patients with estimated creatinine clearance ≤50 mL/min. A single loading dose is followed by maintenance doses beginning at the next dosing interval.

Table 2. Recommended doses for patients with estimated CrCL ≤50 mL/min:

^a Calculated using the Cockcroft-Gault formula.
^b Dose recommendations are based on PK modelling and simulation.
^c Both aztreonam and avibactam are removed by haemodialysis; on haemodialysis days Emblaveo should be administered after the haemodialysis session.
^d Aztreonam-avibactam should not be used in patients with CrCl ≤15 mL/min unless haemodialysis or another form of renal replacement therapy is initiated.

In patients with renal impairment, close monitoring of estimated creatinine clearance is advised (see sections 4.4 and 5.2).

There are insufficient data to make dosing adjustment recommendations for patients undergoing renal replacement therapy other than haemodialysis (e.g. continuous veno-venous hemofiltration or peritoneal dialysis). Patients receiving continuous renal replacement therapy (CRRT) need a higher dose than patients on haemodialysis. For patients receiving continuous renal replacement therapy, the dose should be adjusted guided by the CRRT clearance (CLCRRT in mL/min).

Hepatic impairment

No dosage adjustment is required in patients with hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Emblaveo in paediatric patients <18 years of age have not yet been established. No data are available.

Method of administration

Intravenous use.

Emblaveo is administered by intravenous infusion over 3 hours.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Overdose can cause encephalopathy, confusion, epilepsy, impaired consciousness, and movement disorders particularly in patients with renal impairment (see section 4.4).

If necessary, aztreonam and avibactam may be partially removed by haemodialysis.

During a 4-hour haemodialysis session, 38% of the aztreonam dose and 55% of the avibactam dose is removed.

Dry powder

2 years.

After reconstitution

The reconstituted vial should be used within 30 minutes for preparation of the infusion bag or stock solution that delivers the appropriate dose of ATM-AVI for intravenous infusion.

After dilution

Infusion bags:

If the intravenous solution is prepared with sodium chloride (0.9%) solution for injection or Lactated Ringer’s solution, the chemical and physical in-use stability has been demonstrated for 24 hours at 2°C–8°C followed by up to 12 hours at up to 30°C.

If the intravenous solution is prepared with glucose (5%) solution for injection, the chemical and physical in-use stability has been demonstrated for 24 hours at 2°C–8°C followed by up to 6 hours up to 30°C.

From a microbiological point of view, the medicinal product should be used immediately, unless reconstitution and dilution have taken place in controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and must not exceed those stated above.

Store in a refrigerator (2°C–8°C).

Store in the original package in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

30 mL glass vial (Type I) closed with a rubber (chlorobutyl) stopper and aluminium seal with flip-off cap.

The medicinal product is supplied in packs of 10 vials.

The powder must be reconstituted with sterile water for injections and the resulting concentrate must then be immediately diluted prior to use. The reconstituted solution is a clear, colourless to yellow solution and is free of visible particles.

Standard aseptic techniques should be used for solution preparation and administration. Doses must be prepared in an appropriately sized infusion bag.

Parenteral medicinal products should be inspected visually for particulate matter prior to administration.

Each vial is for single use only.

The total time interval between starting reconstitution and completing preparation of the intravenous infusion should not exceed 30 minutes.

Emblaveo (aztreonam/avibactam) is a combination product; each vial contains 1.5 g of aztreonam and 0.5 g of avibactam in a fixed 3:1 ratio.

Instructions for preparing adult doses in an INFUSION BAG:

NOTE: The following procedure describes the steps to prepare an infusion solution with a final concentration of 1.5-40 mg/mL of aztreonam and 0.50-13.3 mg/mL of avibactam. All calculations should be completed prior to initiating these steps.

1. Prepare the reconstituted solution (131.2 mg/mL of aztreonam and 43.7 mg/mL of avibactam):

a) Insert the needle through the vial closure and inject 10 mL of sterile water for injections.

b) Withdraw the needle and shake the vial gently to give a clear, colourless to yellow solution free of visible particles.

2. Prepare the final solution for infusion (final concentration must be 1.5-40 mg/mL of aztreonam and 0.50-13.3 mg/mL of avibactam):

Infusion bag: Further dilute the reconstituted solution by transferring an appropriately calculated volume of the reconstituted solution to an infusion bag containing any of the following: sodium chloride (0.9%) solution for injection, glucose (5%) solution for injection, or Lactated Ringer’s solution.

Refer to Table 4 below.

Table 4. Preparation of Emblaveo for adult doses in an INFUSION BAG:

^a Dilute to final aztreonam concentration of 1.5-40 mg/mL (final avibactam concentration of 0.50-13.3 mg/mL) for in-use stability up to 24 hours at 2°C–8°C, followed by up to 12 hours up to 30°C for infusion bags containing sodium chloride (0.9%) solution for injection or Lactated Ringer’s solution.
^b Dilute to final aztreonam concentration of 1.5-40 mg/mL (final avibactam concentration of 0.50-13.3 mg/mL) for in-use stability up to 24 hours at 2°C–8°C, followed by up to 6 hours up to 30°C for infusion bags containing glucose (5%) solution for injection.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.