RECARBRIO

(imipenem, cilastatin, and relebactam) for injection 1.25 g

Dosing

Preparation, storage and handling

RECARBRIO™ (imipenem, cilastatin, and relebactam) 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.

Preparation of RECARBRIO solution for intravenous administration

To prepare the infusion solution, contents of the vial must be constituted with the appropriate diluent as instructed below.

Single Dose Vial With 1.25 g of RECARBRIO™ (imipenem, cilastatin, and relebactam)

Vial not actual size.

List of appropriate diluents:

  • 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 it is important to adhere to the following instructions, irrespective of the intended patient’s renal function:

Option 1: For Diluents in Prefilled 100-mL IV Bags, Proceed to Step 2. Option 2: For Diluents Not in Prefilled 100-mL IV Bags: Aseptically Withdraw 100 mL of Diluent. Transfer Diluent to Empty IV Bag

Option 1:

For diluents in prefilled 100-mL IV bags, proceed to step 2.

Option 2:

For diluents not in prefilled 100-mL IV bags:

  • Aseptically withdraw 100 mL of diluent
  • Transfer diluent to empty IV bag
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

Withdraw 20 mL (as two 10 mL aliquots) of diluent from IV bag

Constitute vial with one 10 mL aliquot of diluent

  • The constituted suspension is for intravenous infusion only after dilution in an appropriate infusion solution
Shake Vial Well After Constitution and Transfer Resulting Suspension Into the Remaining 80 mL of the Infusion Bag

Shake vial well after constitution

Transfer suspension into remaining 80 mL of IV bag

Add Second 10 mL Aliquot of Diluent to Vial. Shake Well, Transfer of Suspension to Infusion Solution. Agitate the Resulting Mixture in the Bag Until Clear

Add second 10 mL aliquot of diluent to vial

Shake well

Repeat transfer of suspension to infusion solution

Agitate the resulting mixture in the bag until clear

Preparation of RECARBRIO solution for intravenous administration in patients with renal impairment

For patients with renal impairment, prepare a reduced dose of RECARBRIO (1 g, 0.75 g, or 0.5 g) by preparing a 100 mL solution containing 1.25 g, then withdrawing and discarding the excess as shown below.

Preparation of reduced RECARBRIO doses for intravenous administration in patients with renal impairment

Creatinine Clearance (mL/min) Dosage of RECARBRIO (imipenem, cilastatin, and relebactam) After preparation as instructed above, remove from the 100 mL prepared bag the volume indicated below and discard Resulting volume that provides the indicated reduced dose
60 to 89 1 g (imipenem 400 mg, cilastatin 400 mg, and relebactam 200 mg) 20 mL 80 mL
30 to 59 0.75 g (imipenem 300 mg, cilastatin 300 mg, and relebactam 150 mg) 40 mL 60 mL
15 to 29 or End-Stage Renal Disease on Hemodialysis 0.5 g (imipenem 200 mg, cilastatin 200 mg, and relebactam 100 mg) 60 mL 40 mL

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. Constituted solutions of RECARBRIO range from colorless to yellow. Variations of color within this range do not affect the potency of the product.

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 drug products

The physical compatibility of RECARBRIO with selected injectable drug products was evaluated in 2 commonly available diluents. Compatible drugs with the corresponding compatible diluent (ie, 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP) are listed below.

RECARBRIO should not be co-administered through the same IV 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.

How RECARBRIO is supplied

RECARBRIO™ (imipenem, cilastatin, and relebactam) for injection, 1.25 grams is supplied as a white to light yellow sterile powder for constitution in a single-dose glass vial containing imipenem 500 mg (equivalent to 530 mg imipenem monohydrate), cilastatin 500 mg (equivalent to 531 mg cilastatin sodium), and relebactam 250 mg (equivalent to 263 mg relebactam monohydrate).

Storage and handling of vials

Store RECARBRIO vials at 20 °C to 25 °C (68 °F to 77 °F), excursions permitted between 15 °C to 30 °C (between 59 °F to 86 °F). Keep vials in the carton.

Download the Infusion and Billing Guide for RECARBRIO

Indications

RECARBRIO is indicated for the treatment of patients 18 years of age and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible gram-negative microorganisms: Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens.

RECARBRIO is indicated in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

RECARBRIO is indicated in patients 18 years of age and older who have limited or no alternative treatment options for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible gram-negative microorganisms: Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis, and Pseudomonas aeruginosa.

Approval of the cUTI and cIAI indications is based on limited clinical safety and efficacy data for RECARBRIO.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of RECARBRIO and other antibacterial drugs, RECARBRIO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Selected Safety Information

  • Hypersensitivity Reactions: RECARBRIO is contraindicated in patients with a history of known severe hypersensitivity (severe systemic allergic reaction such as anaphylaxis) to any component of RECARBRIO. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with RECARBRIO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta-lactams, and other allergens. If a hypersensitivity reaction to RECARBRIO occurs, discontinue the therapy immediately.
  • Seizures and Other Central Nervous System (CNS) Adverse Reactions: CNS adverse reactions, such as seizures, confusional states, and myoclonic activity, have been reported during treatment with imipenem/cilastatin, a component of RECARBRIO, especially when recommended dosages of imipenem were exceeded. These have been reported most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) and/or compromised renal function.
  • Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether RECARBRIO should be discontinued.
  • Increased Seizure Potential Due to Interaction with Valproic Acid: Concomitant use of RECARBRIO, with valproic acid or divalproex sodium may increase the risk of breakthrough seizures. Avoid concomitant use of RECARBRIO with valproic acid or divalproex sodium or consider alternative antibacterial drugs other than carbapenems.
  • Clostridioides difficile–Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including RECARBRIO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued.
  • Development of Drug-Resistant Bacteria: Prescribing RECARBRIO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
  • Adverse Reactions: The most frequently reported adverse reactions occurring in ≥2% of cUTI and cIAI patients treated with RECARBRIO were diarrhea (6%), nausea (6%), headache (4%), vomiting (3%), alanine aminotransferase increased (3%), aspartate aminotransferase increased (3%), phlebitis/infusion site reactions (2%), pyrexia (2%), and hypertension (2%). The most frequently reported adverse reactions occurring in ≥5% of HABP/VABP patients treated with RECARBRIO were aspartate aminotransferase increased (11.7%), anemia (10.5%), alanine aminotransferase increased (9.8%), diarrhea (7.9%), hypokalemia (7.9%), and hyponatremia (6.4%).
US-TIX-0010609/20