Imipenem, cilastatin, and relebactam

Recommended Dosage in Adult Patients with Renal Impairment Adult patients who have a CLcr less than 90 mL/min require dosage reduction of RECARBRIO. The recommended dosage of RECARBRIO in adult patients with renal impairment is shown in Table 2 . [See table below.] Do not administer RECARBRIO to adult patients with CLcr less than 15 mL/min unless hemodialysis is instituted within 48 hours after dose administration.

Imipenem, cilastatin, and relebactam are cleared from the circulation during hemodialysis. For adult patients maintained on hemodialysis, administer the recommended dose of RECARBRIO after hemodialysis and at intervals timed from the end of that hemodialysis session. There is inadequate information to recommend dosage of RECARBRIO for adults undergoing peritoneal dialysis.

Recommended Dosage in Pediatric Patients Weighing at Least 30 kg with Renal Impairment Pediatric patients weighing at least 30 kg who have an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73m 2 require dosage reduction of RECARBRIO. The recommended dosage of RECARBRIO in pediatric patients weighing at least 30 kg with renal impairment is shown in Table 3 .

There is insufficient information to recommend a dosage of RECARBRIO for pediatric patients weighing less than 30 kg with any degree of renal impairment. [See table below.] Do not administer RECARBRIO to pediatric patients weighing at least 30 kg with an eGFR less than 15 mL/min/1.73m 2 unless hemodialysis is instituted within 48 hours after dose administration.

Imipenem, cilastatin, and relebactam are cleared from the circulation during hemodialysis. For pediatric patients weighing at least 30 kg maintained on hemodialysis, administer the recommended dose of RECARBRIO after hemodialysis and at intervals timed from the end of that hemodialysis session. There is inadequate information to recommend a dosage of RECARBRIO for pediatric patients undergoing peritoneal dialysis.

Preparation of RECARBRIO Solution for Intravenous Administration 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. To prepare the infusion solution, contents of the vial must be constituted with the appropriate diluent as instructed below.

A list of appropriate diluents is as follows: 0.9% Sodium Chloride Injection, USP 5% Dextrose Injection, USP 5% Dextrose Injection, USP + 0.9% Sodium Chloride Injection, USP 5% Dextrose Injection, USP + 0.45% Sodium Chloride Injection, USP 5% Dextrose Injection, USP + 0.225% Sodium Chloride Injection, USP RECARBRIO has low aqueous solubility.

To ensure complete dissolution of RECARBRIO it is important to adhere to the following instructions: Step 1) For diluents available in 100 mL prefilled infusion bags, proceed to step 2. For diluents not available in 100 mL prefilled infusion bags, aseptically withdraw 100 mL of the desired diluent and transfer it to an empty infusion bag, then proceed to step 2.

Step 2) Withdraw 20 mL (as two 10 mL aliquots) of diluent from the appropriate infusion bag and constitute the vial with one 10 mL aliquot of the diluent. The constituted suspension is for intravenous infusion only after dilution in an appropriate infusion solution. Step 3) After constitution, shake vial well and transfer resulting suspension into the remaining 80 mL of the infusion bag.

Step 4) Add the second 10 mL aliquot 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. Parenteral drug 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. The above instructions for preparation of RECARBRIO solution for intravenous administration must be followed for all patients, irrespective of the intended patient’s renal function, age or weight.

The volume of this prepared RECARBRIO solution to be administered in adult and pediatric (weighing at least 30 kg) patients is determined based on estimated renal function [see Dosage and Administration ] . The volume of the prepared RECARBRIO solution to be administered to pediatric patients weighing 2 kg to less than 30 kg with normal renal function is calculated based on patient weight using the formula below [see Dosage and Administration ]: To achieve the appropriate infusion volume, withdraw and discard the excess (100 mL minus the infusion volume) from the prepared 100 mL solution.

The remaining volume is the appropriate infusion volume. Figure

Preparation of RECARBRIO Solution for Intravenous Administration in Adult and Pediatric Patients Weighing at Least 30 kg with Renal Impairment Prepare a reduced dose of RECARBRIO (1 gram, 0.75 grams, or 0.5 grams) [see Dosage and Administration (2.3 , 2.4) ] by preparing a 100 mL solution containing 1.25 grams as described above [see Dosage and Administration ] then withdrawing and discarding the excess according to Table 4 . [See table below.] 60 mL 15 to 29 not receiving hemodialysis RECARBRIO 0.5 grams Provides 200 mg imipenem, 200 mg cilastatin, and 100 mg relebactam 60 mL 40 mL Receiving hemodialysis RECARBRIO 0.5 grams 60 mL 40 mL

Storage of Constituted Solution RECARBRIO, as supplied in single-dose glass vials upon constitution with the appropriate diluent and following further dilution in the infusion bag, maintains satisfactory potency for at least 2 hours at room temperature (up to 30°C) or for at least 24 hours under refrigeration at 2°C to 8°C (36°F to 46°F).

Do not freeze solutions of RECARBRIO.

Compatible Injectable Drug Products Compatible Drug Products The physical compatibility of RECARBRIO with selected injectable drug products was evaluated in two commonly available diluents. Compatible drugs with the corresponding compatible diluent (i.e., 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP) are listed below.

RECARBRIO should not be co-administered through the same intravenous line (or cannula), with other drug products not listed below, as no compatibility data are available. Refer to the respective prescribing information of the co-administered drug(s) to confirm compatibility of simultaneous co-administration. List of Compatible Injectable Drugs for use with 5% Dextrose USP or 0.9% Sodium Chloride USP Injection as Diluents dexmedetomidine dopamine epinephrine fentanyl heparin midazolam norepinephrine phenylephrine

Incompatible Injectable Drug Products RECARBRIO for injection for intravenous infusion is physically incompatible with propofol in 5% Dextrose USP or 0.9% Sodium Chloride USP.