useful to monitorrenal function. No dosage adjustment is required based on age. Dosage adjustment for elderly patientsshould be based on renal function [see Dosage and Administration (2.2) and Clinical Pharmacology(12.3)].
8.6 Renal Impairment
Reduce RECARBRIO dosage in patients with a CLcr less than 90 mL/min [see Dosage andAdministration (2.2) and Clinical Pharmacology (12.3)].
10 OVERDOSAGE
In the event of overdose, discontinue RECARBRIO, treat symptomatically, and institute generalsupportive treatment. Imipenem, cilastatin, and relebactam can be removed by hemodialysis [see ClinicalPharmacology (12.3)]. No clinical information is available on the use of hemodialysis to treat overdosage.
11 DESCRIPTION
RECARBRIO (imipenem, cilastatin, and relebactam) for injection is an antibacterial combination productconsisting of imipenem, a carbapenem antibacterial drug, cilastatin, a renal dehydropeptidase inhibitor,and relebactam, a diazabicyclooctane beta lactamase inhibitor, for intravenous administration.
ImipenemImipenem is a beta lactam antibacterial drug. Imipenem (N-formimidoylthienamycin monohydrate) is acrystalline derivative of thienamycin, which is produced by Streptomyces cattleya. The chemical name is(5R,6S)-3-[[2-(formimidoylamino)ethyl]thio]-6-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-
carboxylic acid monohydrate. It is an off-white, nonhygroscopic crystalline compound, sparingly soluble inwater. The empirical formula is C12H17N3O4S.H2O and the molecular weight is 317.37.
Figure 1: Chemical structure of imipenem
Cilastatin
Cilastatin sodium is the sodium salt of a derivatized heptenoic acid. The chemical name is sodium (Z)-7-[[(R)-2-amino-2-carboxyethyl]thio]-2-[(S)-2,2-dimethylcyclopropanecarboxamido]-2-heptenoate. It is anoff-white to white, hygroscopic, amorphous compound, very soluble in water. The empirical formula is
C16H25N2NaO5S and the molecular weight is 380.44.
Figure 2: Chemical structure of cilastatin sodium
Relebactam
Relebactam is a beta lactamase inhibitor. It is a crystalline monohydrate. The chemical name is(1R,2S,5R)-7-oxo-2-(piperidin-1-ium-4-ylcarbamoyl)-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate hydrate. It isa white to off-white powder, soluble in water. The empirical formula is C12H20N4O6S.H2O and themolecular weight is 366.39.
Figure 3: Chemical structure of relebactam
RECARBRIO is supplied as a white to light yellow sterile powder for constitution in a single-dose vialcontaining 500 mg imipenem (equivalent to 530 mg imipenem monohydrate), 500 mg cilastatin(equivalent to 531 mg cilastatin sodium), and 250 mg relebactam (equivalent to 263 mg relebactammonohydrate). Each vial of RECARBRIO is buffered with 20 mg sodium bicarbonate to provide solutionsin the pH range of 6.5 to 7.6. The total sodium content of the mixture in the vial is 37.5 mg (1.6 mEq).
Solutions of RECARBRIO range from colorless to yellow. Variations of color within this range do not affectthe potency of the product.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
RECARBRIO is an antibacterial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
For imipenem, the % time of dosing interval that unbound plasma concentrations of imipenem exceed theimipenem/relebactam minimum inhibitory concentration (MIC) (% fT > MIC) against the infecting organismbest correlates with antibacterial activity in animal a |
