Sugammadex

BRIDION ® is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adult and pediatric patients undergoing surgery. BRIDION is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adult and pediatric patients undergoing surgery. ( 1 )

BRIDION (sugammadex) injection is a sterile, clear, colorless to slightly yellow-brown, non-pyrogenic aqueous solution intended for intravenous infusion. BRIDION is available as follows: 200 mg/2 mL (100 mg/mL) in a single-dose vial for bolus injection 500 mg/5 mL (100 mg/mL), in a single-dose vial for bolus injection 200 mg/2 mL (100 mg/mL) in a single-dose vial for bolus injection ( 3 ) 500 mg/5 mL (100 mg/mL) in a single-dose vial for bolus injection ( 3 )

BRIDION is contraindicated in patients with known hypersensitivity to sugammadex or any of its components. Hypersensitivity reactions that occurred varied from isolated skin reactions to serious systemic reactions (i.e., anaphylaxis, anaphylactic shock) and have occurred in patients with no prior exposure to sugammadex [see Warnings and Precautions (5.1) , Adverse Reactions (6) ] . Known hypersensitivity to sugammadex or any of its components. ( 4 )

Anaphylaxis : Be prepared for hypersensitivity reactions (including anaphylactic reactions) and take necessary precautions. ( 5.1 ) Marked Bradycardia : Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after administration. Monitor for hemodynamic changes and administer anticholinergic agents such as atropine if clinically significant bradycardia is observed. ( 5.2 ) Respiratory Function Monitoring : Ventilatory support is mandatory until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Provide adequate ventilation if neuromuscular blockade persists after BRIDION or recurs following extubation. ( 5.3 , 5.4 ) Waiting Times for Re-Administration of Neuromuscular Blocking Agents : If re-administration of a neuromuscular blocking agent is required after reversal with BRIDION, waiting times should be based on the dose of BRIDION and the renal function of the patient. Consider use of a nonsteroidal neuromuscular blocking agent. ( 5.5 )

5.1 Anaphylaxis and Hypersensitivity Clinicians should be prepared for the possibility of drug hypersensitivity reactions (including anaphylactic reactions) and take the necessary precautions [see Contraindications (4) , Adverse Reactions (6.1) ] . Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with BRIDION. The nature and frequency of anaphylaxis and hypersensitivity associated with BRIDION administration were evaluated in a randomized, double-blind, placebo-controlled, parallel-group, repeat-dose study in which 375 subjects were randomized to receive 3 doses of BRIDION IV with a 5-week washout period: 151 subjects received 4 mg/kg, 148 received 16 mg/kg and 76 received placebo. The frequency of anaphylaxis for the 299 healthy volunteers treated with intravenous BRIDION was 0.3% (n=1 in the BRIDION 16 mg/kg group on the first dose). Signs and symptoms included conjunctival edema, urticaria, erythema, swelling of the uvula and reduction in peak expiratory flow within 5 minutes of dose administration. The most common hypersensitivity adverse reactions reported were nausea, pruritus and urticaria and showed a dose response relationship, occurring more frequently in the 16 mg/kg group compared to the 4 mg/kg and placebo groups. Anaphylaxis has also been reported in the post-marketing setting, including at doses less than 16 mg/kg. The most commonly described clinical features in reports of anaphylaxis were dermatologic symptoms (including urticaria, rash, erythema, flushing and skin eruption); and clinically important hypotension often requiring the use of vasopressors for circulatory support. In addition, prolonged hospitalization and/or the use of additional respiratory support until full recovery (re-intubation, prolonged intubation, manual or mechanical ventilation) have been noted in a number of the anaphylaxis reports.

5.2 Marked Bradycardia Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration of BRIDION [see Adverse Reactions (6.2) ] . Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. Treatment with anticholinergic agents, such as atropine, should be administered if clinically significant bradycardia is observed.

5.3 Respiratory Function Monitoring During Recovery Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Even if recovery from neuromuscular blockade is complete, other drugs used in the peri- and post-operative period could depress respiratory function and therefore ventilatory support might still be required. Should neuromuscular blockade persist after BRIDION administration or recur following extubation, take appropriate steps to provide adequate ventilation.

5.4 Risk of Prolonged Neuromuscular Blockade In clinical trials, a small number of patients experienced a delayed or minimal response to the administration of BRIDION [see Clinical Studies (14.1) ] . Thus, it is important to monitor ventilation until recovery occurs.

5.5 Waiting Times for Re-Administration of Neuromuscular Blocking Agents for Intubation Following Reversal with BRIDION A minimum waiting time is necessary before administration of a steroidal neuromuscular blocking agent after administration of BRIDION. Table 1: Re-administration of Rocuronium or Vecuronium after Reversal (up to 4 mg/kg BRIDION) Minimum Waiting Time NMBA and Dose to be Administered 5 minutes 1.2 mg/kg rocuronium 4 hours 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium When rocuronium 1.2 mg/kg is administered within 30 minutes after reversal with BRIDION, the onset of neuromuscular blockade may be delayed up to approximately 4 minutes and the duration of neuromuscular blockade may be shortened up to approximately 15 minutes. The recommended waiting time in patients with mild or moderate renal impairment for re-use of 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium after reversal with up to 4 mg/kg BRIDION should be 24 hours. If a shorter waiting time is required, the rocuronium dose for a new neuromuscular blockade should be 1.2 mg/kg. For re-administration of rocuronium or administration of vecuronium after reversal of rocuronium with 16 mg/kg BRIDION, a waiting time of 24 hours is suggested. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent . The onset of a depolarizing neuromuscular blocking agent might be slower than expected, because a substantial fraction of postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.

5.6 Interactions Potentially Affecting the Efficacy of Other Drugs Due to the administration of BRIDION, certain drugs, including hormonal contraceptives, could become less effective due to a lowering of the (free) plasma concentrations. In this situation, consider the re-administration of the other drug, the administration of a therapeutically equivalent drug (preferably from a different chemical class), and/or non-pharmacological interventions as appropriate [see Drug Interactions (7.3) ] .

5.7 Risk of Recurrence of Neuromuscular Blockade Due to Displacement Interactions Recurrence of neuromuscular blockade may occur due to displacement of rocuronium or vecuronium from BRIDION by other drugs [see Drug Interactions (7.2) ] . In this situation the patient may require mechanical ventilation. Administration of the drug which caused displacement should be stopped in case of an infusion. The risk of displacement reactions will be the highest in the time period equivalent to 3 times the half-life of BRIDION [see Clinical Pharmacology (12.3) ] .

5.8 Risk of Recurrence of Neuromuscular Blockade with Lower Than Recommended Dosing The use of lower than recommended doses of BRIDION may lead to an increased risk of recurrence of neuromuscular blockade after initial reversal and is not recommended [see Dosage and Administration (2.2) , Adverse Reactions (6.1) ] .

5.9 Risk of Recurrence of Neuromuscular Blockade Due to the Administration of Drugs that Potentiate Neuromuscular Blockade When drugs which potentiate neuromuscular blockade are used in the post-operative phase, special attention should be paid to the possibility of recurrence of neuromuscular blockade. Refer to the package insert for rocuronium or vecuronium for a list of the specific drugs which potentiate neuromuscular blockade. In case recurrence of neuromuscular blockade is observed, the patient may require mechanical ventilation. […]

The following serious adverse reactions are described elsewhere in the labeling: Anaphylaxis and Hypersensitivity [see Contraindications (4) , Warnings and Precautions (5.1) ] Marked Bradycardia [see Warnings and Precautions (5.2) ] Most common adverse reactions (reported in ≥10% of adult patients at a 2, 4, or 16 mg/kg BRIDION dose and higher than the placebo rate): vomiting, pain, nausea, hypotension, and headache. ( 6.1 ) Most common adverse reactions (reported in ≥10% of pediatric patients 2 to <17 years of age at BRIDION doses of 2 or 4 mg/kg) were pain, vomiting, and nausea. ( 6.1 ) Most common adverse reaction (reported in ≥10% of pediatric patients from birth to <2 years of age at BRIDION doses of 2 or 4 mg/kg) was procedural pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients The data described below reflect 2914 subjects exposed to 2, 4, or 16 mg/kg BRIDION and 544 to placebo in pooled Phase 1-3 studies. The population was 18 to 92 years old, 47% male and 53% female, 34% ASA (American Society of Anesthesiologists) Class 1, 51% ASA Class 2, and 14% ASA Class 3, and 82% Caucasian. Most subjects received a single dose of BRIDION 2 mg/kg or 4 mg/kg. Adverse reactions reported in ≥10% of patients at a 2, 4, or 16 mg/kg BRIDION dose with a rate higher than the placebo rate are: vomiting, pain, nausea, hypotension, and headache. All adverse reactions occurring in ≥2% of subjects treated with BRIDION and more often than placebo for adult subjects who received anesthesia and/or neuromuscular blocking agent in pooled Phase 1 to 3 studies are presented in Table 2. Table 2: Percent of Subject Exposures in Pooled Phase 1 to 3 Studies with Adverse Reactions Incidence ≥2% Sugammadex Placebo Body System Preferred Term 2 mg/kg (N=895) n (%) 4 mg/kg (N=1921) n (%) 16 mg/kg (N=98) n (%) (N=544) n (%) Injury, poisoning and procedural complications Incision site pain 58 (6) 106 (6) 4 (4) 6 (1) Procedural complication 13 (1) 27 (1) 8 (8) 3 (1) Airway complication of anesthesia 11 (1) 13 (1) 9 (9) 0 Anesthetic complication 8 (1) 14 (1) 9 (9) 1 (<1) Wound hemorrhage 5 (1) 38 (2) 0 8 (1) Recurrence of neuromuscular blockade 0 1 (<1) 2 (2) 0 Gastrointestinal disorders Nausea Combinations of preferred terms are as follows: Nausea includes preferred terms nausea and procedural nausea Vomiting includes preferred terms vomiting and procedural vomiting Abdominal pain includes preferred terms abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, and epigastric discomfort Pain includes preferred terms pain and procedural pain Red blood cell count decreased includes preferred terms red blood cell count decreased, hemoglobin decreased, and hematocrit decreased Electrocardiogram QT interval abnormal includes preferred terms electrocardiogram QT interval abnormal and electrocardiogram QT interval prolonged Hypertension includes preferred terms hypertension, procedural hypertension, and blood pressure increased Hypotension includes preferred terms hypotension, procedural hypotension, and blood pressure decreased Tachycardia includes preferred terms tachycardia and heart rate increased Bradycardia includes preferred terms bradycardia and heart rate decreased 208 (23) 503 (26) 23 (23) 127 (23) Vomiting 98 (11) 236 (12) 15 (15) 57 (10) Abdominal pain 48 (5) 68 (4) 6 (6) 17 (3) Flatulence 17 (2) 51 (3) 1 (1) 10 (2) Dry mouth 9 (1) 5 (<1) 2 (2) 0 General disorders and administration site conditions Pain 434 (48) 993 (52) 35 (36) 207 (38) Pyrexia 77 (9) 109 (6) 5 (5) 17 (3) Chills 30 (3) 61 (3) 7 (7) 27 (5) Nervous system disorders Headache 61 (7) 99 (5) 10 (10) 42 (8) Dizziness 44 (5) 67 (3) 6 (6) 13 (2) Hypoesthesia 12 (1) 24 (1) 3 (3) 9 (2) Respiratory, thoracic and mediastinal disorders Oropharyngeal pain 42 (5) 66 (3) 5 (5) 27 (5) Cough 13 (1) 49 (3) 8 (8) 11 (2) Musculoskeletal and connective tissue disorders Pain in extremity 13 (1) 35 (2) 6 (6) 15 (3) Musculoskeletal pain 16 (2) 33 (2) 1 (1) 6 (1) Myalgia 5 (1) 17 (1) 2 (2) 3 (1) Psychiatric disorders Insomnia 20 (2) 103 (5) 5 (5) 22 (4) Anxiety 14 (2) 19 (1) 3 (3) 1 (<1) Restlessness 3 (<1) 17 (1) 2 (2) 2 (<1) Depression 2 (<1) 5 (<1) 2 (2) 0 Investigations Red blood cell count decreased 13 (1) 34 (2) 1 (1) 2 (<1) Electrocardiogram QT interval abnormal 13 (1) 7 (<1) 6 (6) 4 (1) Blood creatine phosphokinase increased 9 (1) 14 (1) 2 (2) 1 (<1) Vascular disorders Hypertension 48 (5) 96 (5) 9 (9) 38 (7) Hypotension 33 (4) 102 (5) 13 (13) 20 (4) Skin and subcutaneous tissue disorders Pruritus 17 (2) 50 (3) 2 (2) 9 (2) Erythema 5 (1) 31 (2) 0 6 (1) Metabolism and nutrition disorders Hypocalcemia 15 (2) 12 (1) 0 4 (1) Cardiac disorders Tachycardia 17 (2) 29 (2) 5 (5) 4 (1) Bradycardia 9 (1) 21 (1) 5 (5) 6 (1) Surgical and medical procedures Hysterectomy 0 0 2 (2) 0 Pediatric Patients 2 to <17 years of age 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 ≥5% of pediatric patients are presented in Table 3. The safety profile was generally consistent with that observed in adults. Table 3: Pediatric Patients (2 to <17 years of age) with Adverse Events Incidence ≥5% in One or More Treatment Groups Up to 7 Days Post-Treatment Sugammadex 2 mg/kg Sugammadex 4 mg/kg n (%) n (%) Subjects in population 51 191 with one or more specific adverse events 40 (78) 143 (75) with no specific adverse events 11 (22) 48 (25) Cardiac disorders 5 (10) 16 (8) Bradycardia Combines preferred terms of bradycardia and sinus bradycardia Every subject is counted a single time for each applicable row and column. A system organ class or specific adverse event appears in this table only if its incidence in one or more of the columns meets the incidence criterion in the table title, after rounding. 5 (10) 13 (7) Eye disorders 3 (6) 1 (1) Gastrointestinal disorders 8 (16) 35 (18) Nausea 1 (2) 12 (6) Vomiting 4 (8) 20 (10) Injury, poisoning and procedural complications 34 (67) 121 (63) Incision site pain 3 (6) 6 (3) Procedural nausea 4 (8) 9 (5) Procedural pain 30 (59) 111 (58) Procedural vomiting 3 (6) 5 (3) Birth to <2 years of age The safety of BRIDION has been assessed in a randomized, double-blinded, active comparator-controlled study of pediatric patients from birth to <2 years of age, with 107 receiving treatment with BRIDION. Adverse events occurring in ≥5% of pediatric patients are presented in Table 4. The safety profile was generally consistent with that observed in pediatric patients from 2 to <17 years of age and adults. Table 4: Pediatric Participants (Birth to <2 Years) with Specific Adverse Events Incidence ≥ 5% in One or More Treatment Groups Up to 7 Days Post-Treatment Sugammadex 2 mg/kg Sugammadex 4 mg/kg n (%) n (%) Every participant is counted a single time for each applicable row and column. A system organ class or specific adverse event appears in this table only if its incidence in one or more of the columns meets the incidence criterion in the table title, after rounding. […]

Toremifene : Concomitant use can delay recovery. ( 7.2 ) Hormonal contraceptives : Patients must use an additional, non-hormonal method of contraception for 7 days following BRIDION administration. ( 5.6 , 7.3 )

7.1 Summary The information reported in sections 7.2 – 7.4 is based on binding affinity between BRIDION and other drugs, preclinical experiments, clinical studies and simulations of a pharmacokinetic-pharmacodynamic (PK-PD) model. Based on these considerations, no clinically significant pharmacodynamic interactions with other drugs are expected, with the exception of toremifene and hormonal contraceptives.

7.2 Interactions Potentially Affecting the Efficacy of BRIDION Toremifene For toremifene, which has a relatively high binding affinity for sugammadex and for which relatively high plasma concentrations might be present, some displacement of vecuronium or rocuronium from the complex with BRIDION could occur. The recovery to TOF ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of surgery.

7.3 Interaction Potentially Affecting the Efficacy of Hormonal Contraceptives In vitro binding studies indicate that BRIDION may bind to progestogen, thereby decreasing progestogen exposure. Therefore, the administration of a bolus dose of BRIDION is considered to be equivalent to missing dose(s) of oral contraceptives containing an estrogen or progestogen. If an oral contraceptive is taken on the same day that BRIDION is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception (such as condoms and spermicides) for the next 7 days. In the case of non-oral hormonal contraceptives, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception (such as condoms and spermicides) for the next 7 days.

7.4 Interference with Laboratory Tests BRIDION may interfere with the serum progesterone assay. Interference with this test was observed at sugammadex plasma concentrations of 100 mcg/mL, which may be observed for up to 30 minutes after a 16 mg/kg dose.

Severe Renal Impairment : Not recommended. ( 8.6 )

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. However, there was an increase in the incidence of incomplete ossification of the sternebra and reduced fetal body weights in the rabbit study at 8 times the MRHD, which is a dose level in which maternal toxicity was also observed. In a pre- and postnatal development study, sugammadex treatment resulted in an increase in early postnatal loss, which correlated with maternal behavior (increased incidence of pup cannibalism), at exposures equivalent to the MRHD and higher (see Data ) . The background risk of major birth defects and miscarriage for the indicated population are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. 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 [see Nonclinical Toxicology (13.2) ] , it is possible that these findings may be attributable to drug. There was no evidence of malformations at any dose. In a prenatal and postnatal development study, pregnant rats were administered sugammadex intravenously at 0, 30, 120, and 500 mg/kg (0.3, 1, and 6 times the MRHD, respectively, based on AUC comparison) from Gestational Day (GD) 6 to Postnatal Day (PND) 21 (corresponding to the beginning of organogenesis through parturition and subsequent pup weaning). Postnatal loss during PND 1-4 was noted across control litters and treated litters from dams receiving sugammadex as a result of pup cannibalization by dams. Overall incidence of affected litters was 2, 1, 4, and 3 litters, respectively, at 0, 30, 120, or 500 mg/kg/day. The reason for the increased cannibalization is not known. An effect of sugammadex on steroidal hormones and/or pheromones cannot be ruled out. In addition, there were no drug-related effects on parturition in rats during evaluations for prenatal or postnatal development.

8.2 Lactation Risk Summary No data are available regarding the presence of sugammadex in human milk, the effects of sugammadex on the breast fed infant, or the effects of sugammadex on milk production. However, sugammadex is present in rat milk (see Data ) . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BRIDION and any potential adverse effects on the breastfed infant from BRIDION or from the underlying maternal condition. Data In a milk excretion study in rat dams following single intravenous dose of 20 mg/kg sugammadex on Postnatal Day 9, the maximum drug level was achieved at about 30 minutes after dosing with a ratio of milk to plasma level approximately 1:1. The oral exposure via milk did not induce effects on survival, body weight and physical or the behavioral developmental parameters monitored in rats in the prenatal and postnatal development studies [see Use in Specific Populations (8.1) ] .

8.3 Females and Males of Reproductive Potential Contraception Upon administration of BRIDION, the efficacy of hormonal contraceptives may be reduced for up to 7 days. Advise female patients of reproductive potential using hormonal contraceptives to use an additional, non-hormonal contraceptive for the next 7 days following BRIDION administration [see Drug Interactions (7.3) ] .

8.4 Pediatric Use 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. Use of BRIDION in these age groups is supported by evidence from adequate and well-controlled studies of BRIDION [see Clinical Pharmacology (12.3) and Clinical Studies (14.1) ]. In pediatric patients, the safety profile is generally consistent with that observed in adults [see Adverse Reactions (6.1) ] . Juvenile Animal Studies In a bone deposition study, sugammadex concentrations were significantly higher in juvenile rats compared to adult rats (13% vs. 3% of the administered dose, respectively) following a single intravenous (IV) dose at 30 mg/kg (0.3 times the MRHD based on adult AUC comparison). In a juvenile animal bone toxicity study, 7-day old rats were dosed intravenously once daily for 28 days with 0, 30, 120, and 500 mg/kg sugammadex (approximately 0.1, 0.6, and 3 times the MRHD, respectively, by adult AUC comparison). Sugammadex at 120 and 500 mg/kg decreased ulna and femur bone lengths by approximately 3%, which did not recover after an 8-week treatment-free period. Reversible whitish discoloration and disturbance of enamel formation were also observed in the incisors at these dose levels. In molars, this effect was only observed at 500 mg/kg. The no-observed-effect-level (NOEL) was 30 mg/kg. In a second juvenile animal bone toxicity study, 7-day old rats were dosed once weekly for 8 weeks with 0, 7.5, 30, and 120 mg/kg (up to 1.2 times the MRHD of 16 mg/kg based on adult AUC comparison). No adverse effects on bone or teeth were noted.

8.5 Geriatric Use BRIDION has been administered in a dedicated clinical study to a total 102 geriatric patients that compared the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 mg/kg BRIDION given at the reappearance of T 2 in 65-74 year-olds (N=62) and ≥75 year-olds (N=40) compared with 18-64 year-olds (N=48). The median time to recovery of the TOF (T 4 /T 1 ) ratio to 0.9 in 18-64 year-olds was 2.2 minutes; in 65-74 year-olds it was 2.5 minutes, and in ≥75 year-olds it was 3.6 minutes. For time to recovery from neuromuscular blockade induced by rocuronium following administration of 4 mg/kg BRIDION given at 1-2 PTCs, results across clinical trials revealed a median recovery of 2.5 minutes for geriatric patients (≥65 years, N=63) versus 2.0 minutes, for adults aged 18-64 years (N=359). Hence no dose adjustment is necessary in geriatric patients with normal organ function [see Dosage and Administration (2.2) ] . This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . […]

BRIDION is a modified gamma cyclodextrin. It forms a complex with the neuromuscular blocking agents rocuronium and vecuronium, and it reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction. This results in the reversal of neuromuscular blockade induced by rocuronium and vecuronium.