, through mating, and until gestation day (GD) 7.
Relebactam did notimpair fertility, reproductive performance or spermatogenesis in males or fertility, reproductiveperformance, or early embryonic development in females at doses up to 450 mg/kg/day corresponding toplasma AUC exposures of approximately 8 times in males and 7 times in females the plasma AUCexposure in humans at the MRHD.
13.2 Animal Toxicology and/or Pharmacology
Relebactam given as a single entity caused renal tubular degeneration in monkeys at AUC exposure7-fold the human AUC exposure at the MRHD. Renal tubular degeneration was shown to be reversibleafter dose discontinuation. There was no evidence of nephrotoxicity at AUC exposures less than or equalto 3-fold the human AUC exposure at the MRHD.
14 CLINICAL STUDIES
The determination of efficacy and safety of RECARBRIO was supported in part by the previous findingsof the efficacy and safety of imipenem/cilastatin for the treatment of cIAI and cUTI. The contribution ofrelebactam to RECARBRIO was primarily established in vitro and in animal models of infection [seeMicrobiology (12.4)]. Imipenem/cilastatin plus relebactam was studied in cIAI and cUTI includingpyelonephritis in randomized, blinded, active-controlled, multicenter trials. These trials provided onlylimited efficacy and safety information
16 HOW SUPPLIED/STORAGE AND HANDLING
RECARBRIO (imipenem, cilastatin, and relebactam) for injection, 1.25 grams is supplied as a white tolight 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 cilastatinsodium), and relebactam 250 mg (equivalent to 263 mg relebactam monohydrate).
The vials are supplied as a single-dose glass vial (NDC 0006-3856-01) and in cartons containing 25 vials(NDC 0006-3856-02).
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) [See USP Controlled Room Temperature]. Keep vials in the carton.
17 PATIENT COUNSELING INFORMATION
Serious Allergic Reactions
Advise patients, their families, or caregivers that allergic reactions, including serious allergic reactions,could occur that require immediate treatment. Ask them about any previous hypersensitivity reactions toRECARBRIO (imipenem, cilastatin, and relebactam), carbapenems, penicillins, cephalosporins, otherbeta lactams, or other allergens [see Warnings and Precautions (5.1)].
Seizures and Central Nervous System Reactions
Counsel patients, their families, or caregivers to inform a healthcare provider if they have central nervoussystem disorders, such as stroke or history of seizures. Seizures have been reported during treatmentwith imipenem especially when recommended dosages were exceeded and with closely relatedantibacterial drugs [see Warnings and Precautions (5.2)].
Drug Interaction with Valproic Acid
Counsel patients, their families, or caregivers to inform a healthcare provider if they are taking valproicacid or divalproex sodium. If treatment with RECARBRIO is necessary, supplemental anti-convulsantmedication to prevent and/or treat seizures may be needed [see Warnings and Precautions (5.3)].
Potentially Serious Diarrhea
Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterialdrugs, including RECARBRIO an |
