Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

BRIDION (NDA-022225)

(SUGAMMADEX SODIUM)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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12/12/2024 (SUPPL-14)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes to add information from a study of pediatric patients from birth to <2 years of age; please refer to label

8 Use in Specific Populations

8.4 Pediatric Use

Additions and revisions underlined:

The safety and effectiveness of BRIDION for reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide have been established in pediatric patients from birth and older.

06/25/2021 (SUPPL-8)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions underlined

…

Pediatric Patients

The safety of BRIDION has been assessed in a randomized, active-controlled study of pediatric patients 2 to <17 years of age, with 242 receiving treatment with BRIDION. Adverse events occurring in greater than or equal to 5% of pediatric patients are presented in Table 3. The safety profile was generally consistent with that observed in adults.

Table 3: Pediatric Patients with Adverse Events Incidence ?5% in One or More Treatment Groups Up to 7 Days Post-Treatment

Please refer to label to view Table 3

…

8 Use in Specific Populations

8.4 Pediatric Use

Subsection revised; additions underlined

The safety and effectiveness of BRIDION for reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide have been established in pediatric patients aged 2 years and older. Use of BRIDION in these age groups is supported by evidence from an adequate and well-controlled study of BRIDION [see Clinical Pharmacology (12.3) and Clinical Studies (14.1)]. In pediatric patients aged 2 years and older, the safety profile is generally consistent with that observed in adults [see Adverse Reactions (6.1)].

Safety and effectiveness in patients younger than 2 years of age have not been established.

…

01/22/2021 (SUPPL-7)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.11 American Society of Anesthesiologists Class 3 or 4 Patients

(Newly added subsection)

One trial of 331 patients who were assessed as ASA Class 3 or 4 investigated the incidence of treatment- emergent arrhythmias (sinus bradycardia, sinus tachycardia, or other cardiac arrhythmias) after administration of sugammadex.

In patients receiving sugammadex (2 mg/kg, 4 mg/kg, or 16 mg/kg), the number (%) of patients with treatment-emergent sinus bradycardia (up to 35 minutes post-administration of sugammadex) was 1/105 (1.0%) in the 2 mg/kg sugammadex treatment group, 2/107 (1.9%) in the 4 mg/kg sugammadex treatment group, and 5/68 (7.4%) in the 16 mg/kg sugammadex treatment group, compared to 4/51 (7.8%) in the neostigmine (50 µg/kg up to 5 mg maximum dose) + glycopyrrolate (10 µg/kg up to 1 mg maximum dose) treatment group. The number of patients with treatment-emergent sinus tachycardia (up to 35 minutes post- administration of sugammadex) was 7/105 (6.7%) in the 2 mg/kg sugammadex treatment group, 10/107 (9.3%) in the 4 mg/kg sugammadex treatment group, and 6/68 (8.8%) in the 16 mg/kg sugammadex treatment group, compared to 11/51 (21.6%) in the neostigmine + glycopyrrolate treatment group. The number of other treatment-emergent arrhythmias (up to 35 minutes post administration of sugammadex) was 1/105 (1.0%) in the 2 mg/kg sugammadex treatment group, 0/107 (0%) in the 4 mg/kg sugammadex treatment group, and 1/68 (1.5%) in the 16 mg/kg sugammadex treatment group, compared to 1/51 (2.0%) in the neostigmine + glycopyrrolate treatment group. The adverse reaction profiles in ASA Class 3 and 4 patients were generally similar to those in adult patients in pooled Phase 1 to 3 studies; therefore, no dosage adjustment is necessary [see Dosage and Administration (2.1), Adverse Reactions (6.1)].

01/22/2021 (SUPPL-9)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of BRIDION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders: Cases of marked bradycardia and bradycardia with cardiac arrest have been observed within minutes after administration of sugammadex [see Warnings and Precautions (5.2)]. Other cardiac rhythm abnormalities have included atrial fibrillation, atrioventricular block, cardiac/cardiorespiratory arrest, electrocardiographic (ECG) ST segment changes, supraventricular tachycardia/extrasystoles, tachycardia,

ventricular fibrillation, and ventricular tachycardia. Anaphylaxis associated with ECG ST segment changes (elevation or depression) consistent with myocardial ischemia or coronary spasm has also been reported.

General Disorders and Administration Site Conditions: Cases of BRIDION not having the intended effect.

Immune System Disorders: Hypersensitivity events including anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, and Type 1 hypersensitivity have been reported [see Warnings and Precautions (5.1)].

Respiratory, Thoracic, and Mediastinal Disorders: Events of laryngospasm, dyspnea, wheezing, pulmonary edema, and respiratory arrest have been reported.

06/09/2020 (SUPPL-6)

Approved Drug Label (PDF)

8 Use in Specific Populations

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no clinical trial data on BRIDION use in pregnant women to inform any drug-associated risks. The available data from the pharmacovigilance safety database and published literature on BRIDION use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of malformations following daily intravenous administration of sugammadex to rats and rabbits during organogenesis at exposures of up to 6 and 8 times, respectively, the maximum recommended human dose (MRHD) of 16 mg/kg…

Data

Animal Data

In an embryofetal development study in rats, pregnant animals received daily intravenous administration of sugammadex at 0, 20, 100, and 500 mg/kg (0.2, 1, and 6 -times the MRHD of 16 mg/kg/day, respectively, based on AUC comparison) during organogenesis (Gestational Days 6-17). No treatment-related maternal and embryofetal changes were observed.

In another embryofetal development study, pregnant New Zealand white rabbits received daily intravenous administration of sugammadex at 0, 20, 65, 200 mg/kg (0.6, 2, and 8 times the MRHD, respectively, based on AUC comparison) during organogenesis (Gestational Days 6-18). Fetal body weight decreases (10 and 14%, respectively) were observed in the offspring at maternal doses of 65 mg/kg and 200 mg/kg. In addition, incomplete ossification of sternebra, and unossified 1st metacarpal were noted at a maternal dose of 200 mg/kg/day. Maternal toxicity was also observed at 200 mg/kg. Considering the observed effects of sugammadex on bone, it is possible that these findings may be attributable to drug. There was no evidence of malformations at any dose.

8.9 Obese Patients with a BMI greater than or equal to 40 kg/m2

(Newly added subsection)

A trial of 188 obese patients, with a body mass index greater than or equal to 40 kg/m2, investigated the time to recovery from moderate or deep neuromuscular blockade induced by rocuronium or vecuronium. Patients received 2 mg/kg or 4 mg/kg BRIDION, as appropriate for level of block, dosed according to either actual body weight (ABW) or ideal body weight (IBW) in random, double-blinded fashion. Pooled across depth of block and neuromuscular blocking agent, the median time to recover to a train-of-four (TOF) ratio greater than or equal to 0.9 in patients dosed by ABW (1.8 minutes) was statistically significantly faster compared to patients dosed by IBW (3.3 minutes).

The adverse reaction profile was generally similar to the profile in adult patients in pooled Phase 1 to 3 studies. No dosage adjustment is necessary.

10/24/2016 (SUPPL-1)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.5 Geriatric Use

All instances of greater than 75 years have been revised to read greater than or equal to 75 years.

8.6 Renal Impairment

This drug is known to be substantially excreted by the kidney. Effect of mild or moderate renal impairment (creatine clearance greater than or equal to 30 and less than or equal to 80 mL/min) on sugammadex PK and PD was obtained from a study in elderly patients… BRIDION is not recommended for use in patients with severe renal impairment (creatine clearance less than 30 mL/min) due to insufficient … (additions underlined)