Your activity: 293 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Sugammadex: Drug information

Sugammadex: Drug information
(For additional information see "Sugammadex: Patient drug information" and see "Sugammadex: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Bridion
Brand Names: Canada
  • Bridion
Pharmacologic Category
  • Antidote;
  • Selective Relaxant Binding Agent
Dosing: Adult

Note: Dosing based on actual body weight. Doses and timing of administration based on monitoring for twitch responses and the extent of spontaneous recovery that has occurred.

Routine reversal of rocuronium- or vecuronium-induced blockade

Routine reversal of rocuronium- or vecuronium-induced blockade:

IV:

Deep block (at least 1 to 2 post-tetanic counts and prior to the second twitch following train-of-four [TOF] stimulation): 4 mg/kg as a single dose (Geldner 2012).

Moderate block (after appearance of the second twitch following TOF stimulation): 2 mg/kg as a single dose.

Readministration of rocuronium or vecuronium: Following sugammadex use for routine reversal, waiting times for readministration of rocuronium or vecuronium vary greatly (5 minutes to 24 hours) depending on agent, dose, and renal function (consult product labeling); if immediate neuromuscular blockade is needed, a nonsteroidal neuromuscular-blocking agent (eg, cisatracurium or atracurium) may be required.

Immediate reversal of rocuronium-induced blockade

Immediate reversal of rocuronium-induced blockade: IV: 16 mg/kg as a single dose administered soon (~3 minutes) after administration of a single dose of rocuronium 1.2 mg/kg. Note: This dose of sugammadex has not been evaluated following administration of vecuronium.

Readministration of rocuronium or administration of vecuronium: Following sugammadex use for immediate reversal of rocuronium, wait 24 hours before readministering rocuronium or administering vecuronium. If more immediate neuromuscular blockade is needed, a nonsteroidal neuromuscular-blocking agent (eg, cisatracurium or atracurium) may be required.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl 30 to 80 mL/minute: No dosage adjustment necessary. After administration of up to 4 mg/kg of sugammadex and at least 24 hours has elapsed, a neuromuscular blocking agent (ie, rocuronium 0.6 mg/kg or vecuronium 0.1 mg/kg) may be readministered if necessary. If sooner readministration of a neuromuscular blocking agent is required, rocuronium 1.2 mg/kg may be administered (no dosing recommended for vecuronium).

CrCl < 30 mL/minute: Use is not recommended.

Dialysis: Use is not recommended.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution, particularly if accompanied by coagulopathy or severe edema.

Dosing: Pediatric

(For additional information see "Sugammadex: Pediatric drug information")

Routine reversal of rocuronium-induced moderate blockade

Routine reversal of rocuronium-induced moderate blockade: Limited data available: Infants and Children <2 years: IV bolus: 2 mg/kg or 4 mg/kg as a single dose given over 10 seconds (Matsui 2019; Plaud 2009). Dosing based on a multicenter, randomized, parallel-group, dose-finding study in surgical patients (n=91 [63 pediatric patients]; age range: 28 days to 17 years) and a dose-response study in pediatric surgical patients (n=75; age range: 2 to 23 months) (Matsui 2019; Plaud 2009).

Routine reversal of rocuronium- or vecuronium-induced blockade

Routine reversal of rocuronium- or vecuronium-induced blockade:

Note: Dosing based on actual body weight. Doses and timing of administration based on monitoring for twitch responses and the extent of spontaneous recovery that has occurred.

Children ≥2 years and Adolescents:

Deep level of neuromuscular block (ie, spontaneous recovery of twitch response of 1 to 2 post-tetanic counts and zero twitch response following train-of-four [TOF] stimulation): IV bolus: 4 mg/kg as a single dose given over 10 seconds.

Moderate level of neuromuscular block (ie, after appearance of the second twitch following TOF stimulation): IV bolus: 2 mg/kg as a single dose given over 10 seconds.

Readministration of rocuronium or vecuronium: Following sugammadex use for routine reversal, waiting times for readministration of rocuronium or vecuronium vary greatly (5 minutes to 24 hours) depending on agent, dose, and renal function (consult product labeling); if immediate neuromuscular blockade is needed, a nonsteroidal neuromuscular-blocking agent (eg, cisatracurium, atracurium) may be required.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents:

CrCl 30 to 80 mL/minute/1.73 m2: There are no pediatric-specific recommendations in manufacturer's labeling; based on experience in adult patients, no dosage adjustment necessary.

CrCl <30 mL/minute/1.73 m2: Use is not recommended.

Dialysis: Use is not recommended.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution, particularly if accompanied by coagulopathy or severe edema.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

BMI ≥40 kg/m2:

IV: 2 or 4 mg/kg (based on moderate or deep level of block) using actual body weight (Monk 2017; manufacturer's labeling).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Bridion: 200 mg/2 mL (2 mL); 500 mg/5 mL (5 mL)

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Bridion: 100 mg/mL (2 mL, 5 mL)

Administration: Adult

IV: Administer as rapid IV push over 10 seconds (according to the manufacturer); however, some experts suggest administering slow IV push to reduce incidence of serious adverse events (eg, bradycardia or asystole) (Hunter 2018). If administered in same IV line as other products, flush with saline before and after administration of sugammadex.

Administration: Pediatric

IV:

Infants and Children <2 years: In one trial, a dilution was administered over 10 seconds (Plaud 2009); based on experience in older patients, some experts suggest administering slow IV push to reduce the incidence of serious adverse events (eg, bradycardia, asystole) (Hunter 2018).

Children ≥2 years and Adolescents: Administer diluted (10 mg/mL) or undiluted (100 mg/mL) over 10 seconds; however, some experts suggest administering slow IV push to reduce the incidence of serious adverse events (eg, bradycardia, asystole) (Hunter 2018). If administered in same IV line as other products, flush with saline before and after administration of sugammadex.

Use: Labeled Indications

Reversal of rocuronium or vecuronium: Reversal of neuromuscular blockade induced by rocuronium or vecuronium in pediatric patients ≥2 years of age and adults undergoing surgery.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults unless otherwise specified.

>10%:

Cardiovascular: Hypotension (5% to 13%)

Gastrointestinal: Nausea (adults: 26%; children and adolescents: 2% to 6%), vomiting (children, adolescents, and adults: 8% to 15%)

Nervous system: Pain (children, adolescents, and adults: 48% to 59%; includes procedural pain)

1% to 10%:

Cardiovascular: Bradycardia (children, adolescents, and adults: 5% to 10%), ECG abnormality (6%, including prolonged QT interval on ECG), hypertension (9%), tachycardia (2% to 5%)

Dermatologic: Erythema of skin (2%), pruritus (3%)

Endocrine & metabolic: Hypocalcemia (2%)

Gastrointestinal: Abdominal pain (4% to 6%), flatulence (3%), xerostomia (≤2%)

Hematologic & oncologic: Decreased red blood cells (1% to 2%)

Hypersensitivity: Hypersensitivity reaction (7% to 9%; including severe hypersensitivity reaction)

Nervous system: Anxiety (1% to 3%), chills (7%), depression (≤2%), dizziness (3% to 6%), headache (10%), hypoesthesia (3%), insomnia (5%), restlessness (1% to 2%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (1% to 2%), limb pain (6%), musculoskeletal pain (2%), myalgia (2%)

Respiratory: Cough (3% to 8%)

Miscellaneous: Fever (5% to 9%)

<1%:

Hypersensitivity: Anaphylactic shock, anaphylaxis (Ruetzler 2022)

Respiratory: Bronchospasm (Ruetzler 2022)

Frequency not defined: Hematologic & oncologic: Increased INR, prolonged partial thromboplastin time, prolonged prothrombin time

Postmarketing:

Cardiovascular: Atrial fibrillation, atrioventricular block, ST segment changes on ECG, supraventricular extrasystole, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia

Hypersensitivity: Nonimmune anaphylaxis, type I hypersensitivity reaction

Neuromuscular & skeletal: Laryngospasm

Respiratory: Dyspnea, pulmonary edema, wheezing

Contraindications

Hypersensitivity to sugammadex or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Bradycardia: Marked bradycardia and bradycardia with cardiac arrest have been reported, usually within minutes after administration. Monitor closely for hemodynamic changes during and after reversal of neuromuscular blockade; use appropriate pharmacologic treatment (eg, atropine) if significant bradycardia occurs.

• Hypersensitivity: Serious hypersensitivity reactions (including anaphylaxis and anaphylactic shock) have been reported (uncommonly). May occur in patients without prior exposure to sugammadex.

• Recurrence of neuromuscular blockade: Recurrence of neuromuscular blockade has occurred in controlled trials, usually associated with suboptimal dosing. After initial reversal with sugammadex, continue respiratory monitoring and ensure adequate ventilator support remains accessible following extubation. Potentiation of neuromuscular blockade by other drugs used in the post-operative period should also be considered for the possibility of recurrence.

Disease-related concerns:

• Cardiovascular disease: Use caution in patients with cardiovascular disease.

• Hepatic impairment: Use caution in patients with hepatic impairment, particularly if accompanied by coagulopathy or severe edema.

• Impaired hemostasis: Use caution in patients with or at risk for impaired hemostasis (eg, coagulopathies, severe liver impairment, or concurrent use of anticoagulants at therapeutic doses). Dose-dependent transient increases in activated partial thromboplastin time (aPTT) and normalized prothrombin time (PT [INR]) have been observed. In clinical trials, significant effects on bleeding were not observed with low-dose sugammadex alone or in conjunction with therapeutic anticoagulation; high risk patients and those receiving high-dose sugammadex were not adequately studied. Careful monitoring of hemostatic and coagulation parameters is recommended.

• Renal impairment: Use is not recommended in patients with severe renal impairment (CrCl <30 mL/minute) or on dialysis.

Special populations:

• Elderly patients: Use caution in elderly patients; reversal time may be delayed.

Other warnings/precautions:

• Appropriate use: Use in intensive care (ICU) setting has not been evaluated. Do not use sugammadex for neuromuscular blockade induced by nonsteroidal neuromuscular blocking agents (eg, succinylcholine or benzylisoquinolinium compounds) or steroidal agents other than rocuronium or vecuronium.

• Experienced personnel: Must be administered under supervision of experienced health care provider familiar with its use.

• Light anesthesia: Signs of light anesthesia (eg, coughing, grimacing, movement, or suckling of tracheal tube) may become apparent when neuromuscular blockade is reversed intentionally in the middle of anesthesia.

• Respiratory function monitoring: Since other drugs (eg, opioids) used in the peri- and post-operative period may depress respiratory function, ventilatory support is mandatory until adequate spontaneous respiration is restored and ability to maintain a patent airway is assured. In addition, some patients experience a delayed or minimal response to recommended doses of sugammadex.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Anticoagulants: Sugammadex may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Fusidic Acid (Systemic): May diminish the therapeutic effect of Sugammadex. Risk C: Monitor therapy

Hormonal Contraceptives: Sugammadex may diminish the therapeutic effect of Hormonal Contraceptives. Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Risk D: Consider therapy modification

Toremifene: May diminish the therapeutic effect of Sugammadex. Risk C: Monitor therapy

Reproductive Considerations

The effects of hormonal contraception may be decreased following sugammadex administration. An additional nonhormonal contraceptive (eg, condom, spermicide) should be used for 7 days after a dose of sugammadex in women using oral or nonoral hormonal contraception.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Limited information is available related to the use of sugammadex for the reversal of rocuronium-induced neuromuscular blockade after cesarean section (Pühringer 2010; Stourac 2013).

Breastfeeding Considerations

It is not known if sugammadex is excreted into breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Neuromuscular stimulation (eg, post-tetanic counts and train-of-four); ECG monitoring (for bradycardia) during and after administration (Hunter 2018); respiratory function during recovery; monitor for anaphylaxis for at least 5 minutes after administration (Hotta 2016; Nakanishi 2016; Tsur 2014; Ue 2016); hemostatic and coagulation parameters in select patients (clinically significant bleeding has not been reported) (Rahe-Meyer 2014)

Mechanism of Action

Sugammadex is a modified gamma cyclodextrin which is a selective relaxant binding agent. It forms a complex with the neuromuscular-blocking agents rocuronium or vecuronium in plasma, reducing the amount of neuromuscular-blocking agent available to bind to nicotinic receptors in the neuromuscular junction. This results in the reversal of neuromuscular blockade induced by rocuronium or vecuronium.

Pharmacokinetics

Onset: <3 minutes.

Distribution: Vd:

Children ≥2 and Adolescents <17 years: 3 to 10 L.

Adults: 11 to 14 L.

Protein binding: Negligible.

Metabolism: Not metabolized.

Half-life elimination:

Pediatric: ~1 to 2 hours.

Adult: Effective: ~2 hours; Prolonged in renal impairment: Mild renal impairment: 4 hours; Moderate renal impairment: 6 hours; Severe renal impairment: 19 hours.

Excretion: Urine (95% as unchanged drug).

Pharmacokinetics: Additional Considerations

Pediatric: Clearance and volume of distribution increase with increasing age.

Pricing: US

Solution (Bridion Intravenous)

200 mg/2 mL (per mL): $69.25

500 mg/5 mL (per mL): $50.74

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Bridion (AR, AT, AU, BE, BH, BR, CH, CL, CN, CO, CR, CY, CZ, DK, DO, EC, EE, EG, ES, FR, GB, GR, GT, HN, HR, HU, IE, IL, IS, KR, LB, LT, LU, MT, MY, NI, NL, NO, NZ, PA, PH, PL, PT, RO, RU, SE, SG, SI, SK, SV, TH, TR, UA, VN);
  • Inspiromadex (EG)


For country code abbreviations (show table)
  1. Bridion (sugammadex) injection [prescribing information]. Rahway, NJ: Merck Sharp & Dohme LLC: May 2022.
  2. Bridion solution for injection (sugammadex sodium) [product monograph]. Hertfordshire, UK; Merck Sharp & Dohme Limited: 2015.
  3. Bridion solution for injection (sugammadex sodium) [summary of product characteristics]. Haarlem, Netherlands; Merck Sharp & Dohme B.V.: June 2013.
  4. Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anaesthesia. Expert Opin Pharmacother. 2008;9(8):1375-1386. [PubMed 18473711]
  5. Geldner G, Niskanen M, Laurila P, et al. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery. Anaesthesia. 2012;67(9):991-998. doi:10.1111/j.1365-2044.2012.07197.x [PubMed 22698066]
  6. Hotta E, Tamagawa-Mineoka R, Masuda K, et al. Anaphylaxis caused by γ-cyclodextrin in sugammadex. Allergol Int. 2016;65(3):356-358. doi:10.1016/j.alit.2016.02.013. [PubMed 27062217]
  7. Hunter JM, Naguib M. Sugammadex-induced bradycardia and asystole: how great is the risk? Br J Anaesth. 2018;121(1):8-12. doi:10.1016/j.bja.2018.03.003. [PubMed 29935599]
  8. Matsui M, Konishi J, Suzuki T, Sekijima C, Miyazawa N, Yamamoto S. Reversibility of rocuronium-induced deep neuromuscular block with sugammadex in infants and children-a randomized study. Biol Pharm Bull. 2019;42(10):1637-1640. doi:10.1248/bpb.b19-00044 [PubMed 31406051]
  9. Monk TG, Rietbergen H, Woo T, Fennema H. Use of sugammadex in patients with obesity: a pooled analysis. Am J Ther. 2017;24(5):e507-e516. doi:10.1097/MJT.0000000000000305 [PubMed 26398716]
  10. Nakanishi T, Ishida K, Utada K, et al. Anaphylaxis to sugammadex diagnosed by skin prick testing using both sugammadex and a sugammadex-rocuronium mixture. Anaesth Intensive Care. 2016;44(1):122-124. [PubMed 26673602]
  11. Plaud B, Meretoja O, Hofmockel R, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009;110:284-294. [PubMed 19194156 ]
  12. Pühringer FK, Kristen P, Rex C. Sugammadex reversal of rocuronium-induced neuromuscular block in Caesarean section patients: a series of seven cases. Br J Anaesth. 2010;105(5):657-660. [PubMed 20736231]
  13. Rahe-Meyer N, Fennema H, Schulman S, et al. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology. 2014;121(5):969-977. doi: 10.1097/ALN.0000000000000424. [PubMed 25208233]
  14. Ruetzler K, Li K, Chhabada S, et al. Sugammadex versus neostigmine for reversal of residual neuromuscular blocks after surgery: a retrospective cohort analysis of postoperative side effects. Anesth Analg. 2022;134(5):1043-1053. doi:10.1213/ANE.0000000000005842 [PubMed 35020636]
  15. Stourac P, Krikava I, Seidlova J, et al. Sugammadex in a parturient with myotonic dystrophy. Br J Anaesth. 2013;110(4):657-658. [PubMed 23508494]
  16. Tsur A, Kalansky A. Hypersensitivity associated with sugammadex administration: a systematic review. Anaesthesia. 2014;69(11):1251-1257. doi:10.1111/anae.12736. [PubMed 24848211]
  17. Ue KL, Kasternow B, Wagner A, et al. Sugammadex: An emerging trigger of intraoperative anaphylaxis. Ann Allergy Asthma Immunol. 2016;117(6):714-716. doi:10.1016/j.anai.2016.09.428. [PubMed 27789121]
Topic 105866 Version 97.0