Rocuronium Bromide (Page 7 of 7)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

Studies in animals have not been performed with rocuronium bromide to evaluate carcinogenic potential or impairment of fertility. Mutagenicity studies (Ames test, analysis of chromosomal aberrations in mammalian cells, and micronucleus test) conducted with rocuronium bromide did not suggest mutagenic potential.

14 CLINICAL STUDIES

In U.S. clinical studies, a total of 1137 patients received rocuronium bromide injection, including 176 pediatric, 140 geriatric, 55 obstetric, and 766 other adults. Most patients (90%) were ASA physical status I or II, about 9% were ASA III, and 10 patients (undergoing coronary artery bypass grafting or valvular surgery) were ASA IV. In European clinical studies, a total of 1394 patients received rocuronium bromide injection, including 52 pediatric, 128 geriatric (65 years or greater), and 1214 other adults.

14.1 Adult Patients

Intubation using doses of rocuronium bromide 0.6 to 0.85 mg/kg was evaluated in 203 adults in 11 clinical studies. Excellent to good intubating conditions were generally achieved within 2 minutes and maximum block occurred within 3 minutes in most patients. Doses within this range provide clinical relaxation for a median (range) time of 33 (14 to 85) minutes under opioid/nitrous oxide/oxygen anesthesia. Larger doses (0.9 and 1.2 mg/kg) were evaluated in 2 studies with 19 and 16 patients under opioid/nitrous oxide/oxygen anesthesia and provided 58 (27 to 111) and 67 (38 to 160) minutes of clinical relaxation, respectively.

Cardiovascular Disease: In 1 clinical study, 10 patients with clinically significant cardiovascular disease undergoing coronary artery bypass graft received an initial dose of 0.6 mg/kg rocuronium bromide. Neuromuscular block was maintained during surgery with bolus maintenance doses of 0.3 mg/kg. Following induction, continuous 8 mcg/kg/min infusion of rocuronium bromide produced relaxation sufficient to support mechanical ventilation for 6 to 12 hours in the surgical intensive care unit (SICU) while the patients were recovering from surgery.
Rapid Sequence Intubation: Intubation was assessed in patients in 6 clinical studies where anesthesia was induced with either thiopental (3 to 6 mg/kg) or propofol (1.5 to 2.5 mg/kg) in combination with either fentanyl (2 to 5 mcg/kg) or alfentanil (1 mg). Most of the patients also received a premedication such as midazolam or temazepam. Most patients had intubation attempted within 60 to 90 seconds of administration of rocuronium bromide 0.6 mg/kg or succinylcholine 1 to 1.5 mg/kg. Excellent or good intubating conditions were achieved in 119/120 (99% [95% confidence interval: 95% to 99.9%]) patients receiving rocuronium bromide and in 108/110 (98% [94% to 99.8%]) patients receiving succinylcholine. The duration of action of rocuronium bromide 0.6 mg/kg is longer than succinylcholine and at this dose is approximately equivalent to the duration of other intermediate-acting neuromuscular blocking drugs.
Obese Patients: Rocuronium bromide was dosed according to actual body weight (ABW) in most clinical studies. The administration of rocuronium bromide in the 47 of 330 (14%) patients who were at least 30% or more above their ideal body weight (IBW) was not associated with clinically significant differences in the onset, duration, recovery, or reversal of rocuronium bromide -induced neuromuscular block.

In 1 clinical study in obese patients, Rocuronium bromide 0.6 mg/kg was dosed according to ABW (n=12) or IBW (n=11). Obese patients dosed according to IBW had a longer time to maximum block, a shorter median (range) clinical duration of 25 (14 to 29) minutes, and did not achieve intubating conditions comparable to those dosed based on ABW. These results support the recommendation that obese patients be dosed based on actual body weight [see Dosage and Administration (2.6)].
Obstetric Patients: Rocuronium bromide 0.6 mg/kg was administered with thiopental, 3 to 4 mg/kg (n=13) or 4 to 6 mg/kg (n=42), for rapid sequence induction of anesthesia for Cesarean section. No neonate had APGAR scores greater than 7 at 5 minutes. The umbilical venous plasma concentrations were 18% of maternal concentrations at delivery. Intubating conditions were poor or inadequate in 5 of 13 women receiving 3 to 4 mg/kg thiopental when intubation was attempted 60 seconds after drug injection. Therefore, Rocuronium bromide is not recommended for rapid sequence induction in Cesarean section patients.

14.2 Geriatric Patients

Rocuronium bromide was evaluated in 55 geriatric patients (ages 65 to 80 years) in 6 clinical studies. Doses of 0.6 mg/kg provided excellent to good intubating conditions in a median (range) time of 2.3 (1 to 8) minutes. Recovery times from 25% to 75% after these doses were not prolonged in geriatric patients compared to other adult patients [see Dosage and Administration (2.6) and Use in Specific Populations (8.5)].

14.3 Pediatric Patients

Rocuronium bromide 0.45, 0.6, or 1 mg/kg was evaluated under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anesthesia for intubation in 326 patients in 2 studies. In 1 of these studies maintenance bolus and infusion requirements were evaluated in 137 patients. In all age groups, doses of 0.6 mg/kg provided time to maximum block in about 1 minute. Across all age groups, median (range) time to reappearance of T3 for doses of 0.6 mg/kg was shortest in the children [36.7 (20.1 to 65.9) minutes] and longest in infants [59.8 (32.3 to 87.8) minutes]. For pediatric patients older than 3 months, the time to recovery was shorter after stopping infusion maintenance when compared with bolus maintenance [see Dosage and Administration (2.6) and Use in Specific Populations (8.4)]. Rocuronium bromide 0.6 or 0.8 mg/kg was evaluated for intubation in 75 pediatric patients (n=28; age 3 to 12 months, n=47; age 1 to 12 years) in 3 studies using halothane (1% to 5%) and nitrous oxide (60% to 70%) in oxygen. Doses of 0.6 mg/kg provided a median (range) time to maximum block of 1 (0.5 to 3.3) minute(s). This dose provided a median (range) time of clinical relaxation of 41 (24 to 68) minutes in 3- month to 1-year-old infants and 26 (17 to 39) minutes in 1- to 12-year-old pediatric patients [see Dosage and Administration (2.6) and Use in Specific Populations (8.4)] .

16 HOW SUPPLIED/STORAGE AND HANDLING

Rocuronium Bromide Injection is supplied as follows:

NDC Rocuronium Bromide Injection (10 mg/mL) Package Factor
68083-364-10 50 mg/5 mL Multiple Dose Vial 10 vials per carton
68083-365-10 100 mg/10 mL Multiple Dose Vial 10 vials per carton

Storage Conditions

Rocuronium bromide Injection should be stored in a refrigerator, 2° to 8°C (36° to 46°F). DO NOT FREEZE. Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use rocuronium bromide within 60 days. Use opened vials of rocuronium bromide within 30 days.

Safety and Handling

17 PATIENT COUNSELING INFORMATION

Obtain information about your patient’s medical history, current medications, any history of hypersensitivity to rocuronium bromide or other neuromuscular blocking agents. If applicable, inform your patients that certain medical conditions and medications might influence how rocuronium bromide works.
In addition, inform your patient that severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium bromide, have been reported. Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents.
Manufactured by:
Gland Pharma Limited
Hyderabad-500 043, INDIA
September 2018

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Rocuronium Bromide Injection,
50 mg/5 mL,
5 mL Multiple dose vial
5 mL Vial label

Rocuronium-vial-label1
(click image for full-size original)

Rocuronium Bromide Injection,
50 mg/5 mL,
5 mL Multiple dose vial
5 mL Carton label

Rocuronium-carton1
(click image for full-size original)

Rocuronium Bromide Injection,
100 mg/10 mL,
10 mL Multiple dose vial
10 mL Vial label
Rocuronium-vial-label2
(click image for full-size original)

Rocuronium Bromide Injection,
100 mg/10 mL,
10 mL Multiple dose vial
10mL Carton Label
Rocuronium-carton2
(click image for full-size original)

ROCURONIUM BROMIDE rocuronium bromide injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68083-364
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROCURONIUM BROMIDE (ROCURONIUM) ROCURONIUM BROMIDE 10 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
ACETIC ACID
SODIUM HYDROXIDE
SODIUM CHLORIDE 3.10 mg in 1 mL
SODIUM ACETATE 2 mg in 1 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:68083-364-10 10 VIAL, MULTI-DOSE in 1 CARTON contains a VIAL, MULTI-DOSE (68083-364-01)
1 NDC:68083-364-01 5 mL in 1 VIAL, MULTI-DOSE This package is contained within the CARTON (68083-364-10)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205656 05/18/2018
ROCURONIUM BROMIDE rocuronium bromide injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68083-365
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ROCURONIUM BROMIDE (ROCURONIUM) ROCURONIUM BROMIDE 10 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
ACETIC ACID
SODIUM HYDROXIDE
SODIUM CHLORIDE 3.10 mg in 1 mL
SODIUM ACETATE 2 mg in 1 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:68083-365-10 10 VIAL, MULTI-DOSE in 1 CARTON contains a VIAL, MULTI-DOSE (68083-365-01)
1 NDC:68083-365-01 10 mL in 1 VIAL, MULTI-DOSE This package is contained within the CARTON (68083-365-10)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA205656 05/18/2018
Labeler — Gland Pharma Limited (918601238)
Establishment
Name Address ID/FEI Operations
GLAND PHARMA LIMITED 918601238 ANALYSIS (68083-364), ANALYSIS (68083-365), MANUFACTURE (68083-364), MANUFACTURE (68083-365), PACK (68083-364), PACK (68083-365)

Revised: 04/2019 Gland Pharma Limited

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