RECARBRIO Powder for solution for infusion Ref.[10656] Active ingredients: Cilastatin Imipemide Imipenem, Cilastatin and Relebactam

It is recommended that Recarbrio 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

Table 1 shows the recommended intravenous dose for patients with a creatinine clearance (CrCl) ≥90 mL/min (see sections 4.4 and 5.1).

Table 1. Recommended intravenous dose for patients with a creatinine clearance (CrCl) ≥90 mL/min^1,2:

¹ As calculated using the Cockcroft-Gault formula.
² For HAP or VAP patients with CrCl ˃250 mL/min, and for patients with complicated intra-abdominal infections (cIAI) or complicated urinary tract infections (cUTI), including pyelonephritis with CrCl ˃150 mL/min, the recommended dose of Recarbrio may not be sufficient (see section 4.4).
³ Includes bacteraemia, in association with, or suspected to be associated with, HAP or VAP.
⁴ e.g., for cIAI and cUTI the recommended treatment duration is 5 to 10 days; treatment may continue up to 14 days.

Special populations

Renal impairment

Patients who have a CrCl less than 90 mL/min require dosage reduction of Recarbrio as indicated in Table 2. For patients with fluctuating renal function, CrCl should be monitored.

Table 2. Recommended intravenous doses for patients with a CrCl <90 mL/min:

^* CrCl calculated using the Cockcroft-Gault formula.
^† Administer intravenously over 30 minutes every 6 hours.
^‡ Administration should be timed to follow haemodialysis. Imipenem, cilastatin, and relebactam are cleared from the circulation during haemodialysis.
Recarbrio is provided as a single vial in a fixed-dose combination; the dose for each component will be adjusted equally during preparation (see section 6.6).

Patients with CrCl less than 15 mL/min should not receive Recarbrio unless haemodialysis is instituted within 48 hours. There is inadequate information to recommend usage of Recarbrio for patients undergoing peritoneal dialysis.

Hepatic impairment

No dose adjustment is required in patients with impaired hepatic function (see section 5.2).

Elderly population

No dose adjustment is required for elderly patients (see section 5.2).

Paediatric population

The safety and efficacy of imipenem/cilastatin/relebactam in children and adolescents below 18 years of age have not yet been established. No data are available.

Method of administration

Intravenous use.

Recarbrio is administered by intravenous infusion over 30 minutes.

Recarbrio must be reconstituted (see sections 6.2, 6.3, and 6.6) prior to intravenous infusion.

In the event of overdose, discontinue Recarbrio, treat based on symptoms, and institute general supportive treatment. Imipenem, cilastatin, and relebactam can be removed by haemodialysis. No clinical information is available on the use of haemodialysis to treat overdosage.

Dry powder: 30 months.

After constitution and dilution: Diluted solutions should be used immediately. The time interval between the beginning of reconstitution and the end of intravenous infusion should not exceed two hours.

This medicinal product does not require any special temperature storage conditions.

Keep vials in the outer carton in order to protect from light.

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

20 mL glass vial, with 20 mm rubber stopper and aluminium crimp cap seal.

This medicinal product is supplied in packs of 25 vials.

Recarbrio is supplied as a dry powder in a single-dose vial that must be constituted and further diluted using aseptic technique prior to intravenous infusion as outlined below:

• To prepare the infusion solution, contents of the vial must be transferred to 100 mL of an appropriate infusion solution (see sections 6.2 and 6.3): 9 mg/mL (0.9%) sodium chloride. In exceptional circumstances where 9 mg/mL (0.9%) sodium chloride cannot be used for clinical reasons 5% glucose may be used instead.
• Withdraw 20 mL (10 mL times 2) of diluent from the appropriate infusion bag and constitute the vial with 10 mL of the diluent. The constituted suspension must not be administered by direct intravenous infusion.
• After constitution, shake vial well and transfer resulting suspension into the remaining 80 mL of the infusion bag.
• Add the additional 10 mL of infusion diluent to the vial and shake well to ensure complete transfer of vial contents; repeat transfer of the resulting suspension to the infusion solution before administering. Agitate the resulting mixture until clear.
• Constituted solutions of Recarbrio range from colorless to yellow. Variations of color within this range do not affect the potency of the product.
• For patients with renal insufficiency, a reduced dose of Recarbrio will be administered according to the patient’s CrCl, as determined from Table 7. Prepare 100 mL of infusion solution as directed above. Select the volume (mL) of the final infusion solution needed for the appropriate dose of Recarbrio as shown in Table 7.

Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if discoloration or visible particles are observed.

Table 7. Preparation of Recarbrio doses:

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

Compatible medicinal products

The physical compatibility of Recarbrio with selected injectable medicinal products was evaluated in two commonly available diluents at a Y-infusion site. Compatible medicinal products with the corresponding compatible diluent (i.e., 5% Dextrose Injection or 0.9% Sodium chloride Injection) are listed below. Recarbrio should not be co-administered through the same intravenous line (or cannula), with other medicinal products not listed below, as no compatibility data are available. Refer to the respective prescribing information of the co-administered medicinal product(s) to confirm compatibility of simultaneous co-administration. This medicinal product must not be mixed with other medicinal products except those mentioned below.

List of Compatible Injectable Medicinal Products for use with 5% Dextrose or 0.9% Sodium chloride Injection as Diluents:

• dexmedetomidine
• dopamine
• epinephrine
• fentanyl
• heparin
• midazolam
• norepinephrine
• phenylephrine

Compatible intravenous bags and infusion set materials

Recarbrio is compatible with the following intravenous container bags and infusion set materials. Any intravenous bags or infusion set materials not listed below should not be used.

Intravenous Container Bag Materials: Polyvinyl chloride (PVC) and polyolefin (polypropylene and polyethylene)

Intravenous Infusion Set Materials: (with tubing) PVC + Di-(2-ethylhexyl)phthalate (DEHP) and polyethylene (PE)-lined PVC

Incompatible medicinal products

Recarbrio for solution for infusion is physically incompatible with propofol in 5% Dextrose (also named Glucose) or 0.9% Sodium chloride.