Efficacy for BRIDION^® (sugammadex)

Recovery in special patient populations

Following rocuronium-induced NMB, choose BRIDION^® (sugammadex) to achieve rapid recovery.

Clinically relevant recovery is defined as a TOF ratio ≥0.9¹

Median time from start of BRIDION or neostigmine administration to a recovery of a TOF ratio of 0.9 with moderate and deep block.

Median time from start of BRIDION or neostigmine administration to a recovery of a TOF ratio of 0.9 with moderate block.

Median time from start of BRIDION administration to a recovery of a TOF ratio of 0.9 with deep block.

^aThere were 7 censored observations in the rocuronium group.

Moderate block study design^2,3

Multicenter, randomized, parallel-group, active-controlled, safety-assessor-blinded study compared the efficacy of 2 mg/kg of BRIDION vs 50 μg/kg of neostigmine and 10 μg/kg of glycopyrrolate for reversal of rocuronium- or vecuronium-induced moderate NMB (reappearance of T₂) in 189 patients (87 women and 102 men, ASA majority class 1, 2). Patients underwent elective procedures that were mainly endocrine; ocular; ear, nose, and throat; abdominal (gynecological, colorectal, urological); orthopedic; vascular; or dermatological in nature. An objective monitoring device (TOF-Watch® SX) was used to evaluate neuromuscular function, to measure the depth of block based on responses to TOF stimulation (TOF count or twitches), and to calculate the degree of recovery using TOF ratio (which cannot be calculated without an objective monitoring device).^1,4 The primary endpoint was the time from start of BRIDION or neostigmine administration to a TOF ratio of 0.9, which generally correlates with recovery from NMB.

Deep block study design^5,6

Multicenter, randomized, parallel-group, active-controlled, safety-assessor-blinded study compared the efficacy of 4 mg/kg of BRIDION vs 70 μg/kg of neostigmine and 14 μg/kg of glycopyrrolate for reversal of rocuronium- or vecuronium-induced deep NMB (1-2 PTCs) in 157 patients (86 women and 71 men, American Society of Anesthesiologists class 1-3). Patients underwent elective surgical procedures that were mainly abdominal (gynecological, colorectal, urological), orthopedic, reconstructive, or neurological in nature. An objective monitoring device (TOF-Watch® SX) was used to evaluate neuromuscular function, to measure the depth of block based on responses to TOF or PTC stimulation, and to calculate the degree of recovery using TOF ratio (which cannot be calculated without an objective monitoring device).^1,7 The primary endpoint was the time from start of BRIDION or neostigmine administration to recovery of a TOF ratio of 0.9, which generally correlates with recovery from NMB.

BRIDION^® (sugammadex) demonstrated efficacy with no dose adjustments in these special patient populations:

Geriatric patients

Recovery in geriatric patients with moderate block

In a dedicated clinical study of geriatric patients (n=102) that compared the time to recovery from rocuronium-induced moderate neuromuscular blockade (NMB), BRIDION demonstrated time to recovery of the train-of-four (TOF) ratio to 0.9 comparable with other treatment groups.⁸

Median time from start of 2 mg/kg of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients.

Median time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients (aged: 18 to 64 years) with moderate block.

Median time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients (aged: 65 to 74 years and ≥75 years) with moderate block.

Study design⁸

Multicenter, parallel-group, open-label study compared the efficacy of 2 mg/kg of BRIDION for reversal of rocuronium-induced moderate NMB (reappearance of T₂) in 48 adult patients (18-64 years), 62 geriatric patients (65-74 years), and 40 older geriatric patients (≥75 years) (American Society of Anesthesiologists [ASA] class 1-3). The primary endpoint was the time from start of BRIDION administration to a TOF ratio (T₄/ T₁) of 0.9.

Recovery in geriatric patients with deep block

In an analysis of pooled clinical trial data, BRIDION demonstrated rapid reversal of rocuronium-induced deep NMB (TOF count of 0, 1-2 post-tetanic counts [PTCs]) to recovery of the TOF ratio to 0.9 in geriatric patients.

Median time from start of 4 mg/kg of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients.

Median Time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients (aged: 18 to 64 years) with deep block.

Median time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in geriatric patients (aged: 65 to 74 years and ≥75 years) with deep block.

No dose adjustment is necessary in geriatric patients with normal organ function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection.

Explore other special patient populations

Cardiac patients

Recovery in cardiac patients with moderate block

In a clinical study, BRIDION provided reversal of rocuronium-induced moderate NMB (reappearance of T₂) to recovery of the TOF ratio to 0.9 in patients diagnosed with or having a history of cardiac disease.⁹

Median time from start of BRIDION administration to a TOF Ratio of 0.9 in cardiac patients with moderate block.

Study design⁹

Multicenter, randomized, parallel-group, placebo-controlled, safety-assessor-blinded study compared the safety and efficacy of 2 mg/kg and 4 mg/kg of BRIDION for reversal of rocuronium-induced moderate NMB (reappearance of T₂) in 76 patients who were diagnosed with or have a history of cardiac disease (eg, patients with ischemic disease, chronic heart failure, or arrhythmia), primarily New York Heart Association (NYHA) Class II. The primary endpoint was to evaluate the safety of BRIDION 2 mg/kg and 4 mg/kg, with the time from start of BRIDION administration to a TOF ratio of 0.9 as a secondary endpoint.

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Pulmonary patients

Recovery in pulmonary patients with moderate block

In a clinical study, BRIDION achieved rapid reversal of rocuronium-induced moderate NMB (reappearance of T₂) to recovery of the TOF ratio to 0.9 in patients diagnosed with or having a history of pulmonary complications.¹⁰

Median time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in pulmonary patients for moderate block.

Study design¹⁰

Multicenter, randomized, parallel-group, comparative, safety-assessor-blinded study compared the safety and efficacy of 2 mg/kg and 4 mg/kg of BRIDION for reversal of rocuronium-induced moderate NMB (reappearance of T₂) in 77 patients who were diagnosed with or have a history of pulmonary complications (ASA class 2 and 3). The primary objective was to evaluate the safety of BRIDION 2 mg/kg and 4 mg/kg, with the time from start of BRIDION administration to a TOF ratio of 0.9 as a primary efficacy objective.

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Obese patients

Recovery in obese^a patients

In a study of obese patients (n=188), BRIDION demonstrated statistically significantly faster recovery in patients dosed by ABW compared to IBW pooled across NMB (moderate or deep) and neuromuscular blocking agent (rocuronium or vecuronium).¹¹

^aObese is defined as a BMI ≥40 kg/m²

Median time from start of BRIDION administration to recovery of a TOF ratio of 0.9 in obese patients dosed by ideal body weight vs actual body weight for moderate and deep block.

Study design¹¹

Exploratory endpoint: BRIDION and neostigmine in obese patients

Exploratory median times to a recovery (TOF ratio of ≥0.9) from moderate block pooled across NMBA

The study was not designed for a comparative analysis on this exploratory endpoint and the exploratory results must be interpreted with caution.

Study design¹¹

Randomized, double-blind trial in 188 obese patients investigated the time to recovery from moderate or deep neuromuscular blockade (NMB) 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 ABW or IBW. Pooled across depth of block and neuromuscular agent, the primary endpoint, ie, the median time to recover to a TOF ratio ≥0.9 in patients dosed by ABW (1.8 minutes), was statistically significantly faster compared to the patients dosed by IBW (3.3 minutes). An exploratory endpoint of the study was to understand the distributions of recovery times for BRIDION and neostigmine in moderate depth of block pooled across NMBA.

Explore other special patient populations

Abbreviations

ABW = actual body weight
ASA = American Society of Anesthesiologists
BMI = body mass index
CI = confidence interval
IBW = ideal body weight
NMB = neuromuscular blockade
NMBA = neuromuscular blocking agent
NYHA = New York Heart Association
PTC = post-tetanic count
TOF = train-of-four
T₂ = second twitch

References

Claudius C, Fuchs-Buder T. Neuromuscular monitoring. In: Gropper MA, ed. Miller’s Anesthesia. 9th ed. Elsevier; 2020:1354-1372.
Blobner M, Eriksson LI, Scholz J, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010;27(10):874-881.
Khuenl-Brady KS, Wattwil M, Vanacker BF, et al. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010;110(1):64-73.
Data available on request from Merck & Co., Inc. Professional Services-DAP, WPI-127, PO Box 4, West Point, PA 19486. Please specify information package US-XBR-02069.
Jones RK, Caldwell JE, Brull SJ, et al. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigimine. Anesthesiology. 2008:109(5):816-824.
Lemmens HJ, El-Orbany Ml, Berry J, et al. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC Anesthesiol. 2010;10:15.
Data available on request from Merck & Co., Inc., Professional Services-DAP, WPl-127, PO Box 4, West Point, PA 19486. Please specify information package US-XBR-02068.
McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy, safety, and pharmacokinetics of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology. 2011;114(2):318-329.
Dahl V, Pendeville PE, Hollmann MW, et al. Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in cardiac patients undergoing noncardiac surgery. Eur J Anaesthesiol. 2009;26(10):874-884.
Amao R, Zornow MH, Cowan RM, et al. Use of sugammadex in patients with a history of pulmonary disease. J Clin Anesth. 2012;24(4):289-297.
Horrow JC, Li W, Blobner M, et al. Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial. BMC Anesthesiol. 2021;21(1):62.

Selected Safety Information

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.
Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with BRIDION. In a clinical study, anaphylaxis occurred in 0.3% (n=1/299) of healthy volunteers treated with BRIDION. 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. Observe patients for an appropriate period of time after administration and take the necessary precautions. Anaphylaxis has also been reported in the post-marketing setting. Clinical features in anaphylaxis reports have included dermatologic symptoms; hypotension often requiring the use of vasopressors; and prolonged hospitalization and/or the use of additional respiratory support until full recovery.
Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration of BRIDION. Monitor for hemodynamic changes and treat with anticholinergic agents, such as atropine, if clinically significant bradycardia is observed.
Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Should neuromuscular blockade persist after BRIDION or recur following extubation, take appropriate steps to provide adequate ventilation.
In clinical trials, a small number of patients experienced a delayed or minimal response to BRIDION. Monitor ventilation until recovery occurs.
A minimum waiting time is necessary before re-administration of a steroidal neuromuscular blocking agent after administration of BRIDION.

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

If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent.

Due to the administration of BRIDION, certain drugs, including hormonal contraceptives, could become less effective due to a lowering of the (free) plasma concentrations. Consider re-administration of the other drug, administration of a therapeutic equivalent drug, and/or non-pharmacological interventions as appropriate. 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.
Recurrence of neuromuscular blockade may occur due to displacement of rocuronium or vecuronium from BRIDION by other drugs. Mechanical ventilation may be required. Stop the administration of the drug which caused displacement, if being administered by infusion.
The use of lower than recommended doses of BRIDION may lead to an increased risk of recurrence of neuromuscular blockade and is not recommended. Also, when drugs which potentiate neuromuscular blockade are used in the post-operative phase, recurrence of neuromuscular blockade is possible.
BRIDION doses of up to 16 mg/kg were associated with increases in activated partial thromboplastin time and prothrombin time/international normalized ratio. Carefully monitor coagulation parameters in patients with known coagulopathies; being treated with therapeutic anticoagulation; receiving thromboprophylaxis drugs other than heparin and low molecular weight heparin; or receiving thromboprophylaxis drugs and who then receive a dose of 16 mg/kg sugammadex.
BRIDION is not recommended for use in patients with severe renal impairment, including those requiring dialysis.
BRIDION has not been studied for reversal following rocuronium or vecuronium administration in the ICU.
Do not use BRIDION to reverse nonsteroidal neuromuscular blocking agents or steroidal neuromuscular blocking agents other than rocuronium or vecuronium.
The most common adverse reactions (reported in ≥ 10% of adult patients at a 2, 4, or 16 mg/kg BRIDION dose and higher than placebo rate) were vomiting (11%, 12%, or 15% versus placebo at 10%), pain (48%, 52%, or 36% versus placebo at 38%), nausea (23%, 26%, or 23% versus placebo at 23%), hypotension (4%, 5%, or 13% versus placebo at 4%), and headache (7%, 5%, or 10% versus placebo at 8%). The 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 (65% and 61%), vomiting (14% and 13%), and nausea (10% and 11%). The most common adverse reactions (reported in ≥ 10% of pediatric patients birth to < 2 years of age at BRIDION doses of 2 or 4 mg/kg) was procedural pain (40.9% and 58%).

Before administering BRIDION® (sugammadex), please read the Prescribing Information.

Indication Indication

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

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

Selected Safety Information Selected Safety Information

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.
Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with BRIDION. In a clinical study, anaphylaxis occurred in 0.3% (n=1/299) of healthy volunteers treated with BRIDION. 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. Observe patients for an appropriate period of time after administration and take the necessary precautions. Anaphylaxis has also been reported in the post-marketing setting. Clinical features in anaphylaxis reports have included dermatologic symptoms; hypotension often requiring the use of vasopressors; and prolonged hospitalization and/or the use of additional respiratory support until full recovery.
Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration of BRIDION. Monitor for hemodynamic changes and treat with anticholinergic agents, such as atropine, if clinically significant bradycardia is observed.
Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Should neuromuscular blockade persist after BRIDION or recur following extubation, take appropriate steps to provide adequate ventilation.
In clinical trials, a small number of patients experienced a delayed or minimal response to BRIDION. Monitor ventilation until recovery occurs.
A minimum waiting time is necessary before re-administration of a steroidal neuromuscular blocking agent after administration of BRIDION.

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

If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent.

Due to the administration of BRIDION, certain drugs, including hormonal contraceptives, could become less effective due to a lowering of the (free) plasma concentrations. Consider re-administration of the other drug, administration of a therapeutic equivalent drug, and/or non-pharmacological interventions as appropriate. 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.
Recurrence of neuromuscular blockade may occur due to displacement of rocuronium or vecuronium from BRIDION by other drugs. Mechanical ventilation may be required. Stop the administration of the drug which caused displacement, if being administered by infusion.
The use of lower than recommended doses of BRIDION may lead to an increased risk of recurrence of neuromuscular blockade and is not recommended. Also, when drugs which potentiate neuromuscular blockade are used in the post-operative phase, recurrence of neuromuscular blockade is possible.
BRIDION doses of up to 16 mg/kg were associated with increases in activated partial thromboplastin time and prothrombin time/international normalized ratio. Carefully monitor coagulation parameters in patients with known coagulopathies; being treated with therapeutic anticoagulation; receiving thromboprophylaxis drugs other than heparin and low molecular weight heparin; or receiving thromboprophylaxis drugs and who then receive a dose of 16 mg/kg sugammadex.
BRIDION is not recommended for use in patients with severe renal impairment, including those requiring dialysis.
BRIDION has not been studied for reversal following rocuronium or vecuronium administration in the ICU.
Do not use BRIDION to reverse nonsteroidal neuromuscular blocking agents or steroidal neuromuscular blocking agents other than rocuronium or vecuronium.
The most common adverse reactions (reported in ≥ 10% of adult patients at a 2, 4, or 16 mg/kg BRIDION dose and higher than placebo rate) were vomiting (11%, 12%, or 15% versus placebo at 10%), pain (48%, 52%, or 36% versus placebo at 38%), nausea (23%, 26%, or 23% versus placebo at 23%), hypotension (4%, 5%, or 13% versus placebo at 4%), and headache (7%, 5%, or 10% versus placebo at 8%). The 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 (65% and 61%), vomiting (14% and 13%), and nausea (10% and 11%). The most common adverse reactions (reported in ≥ 10% of pediatric patients birth to < 2 years of age at BRIDION doses of 2 or 4 mg/kg) was procedural pain (40.9% and 58%).

Before administering BRIDION® (sugammadex), please read the Prescribing Information.

BRIDION is contraindicated in patients with known

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.

Efficacy for BRIDION^® (sugammadex)