Sugammadex

Dosage Forms

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

Solution, Intravenous:

Bridion: 200 mg/2 mL (2 mL)

Solution, Intravenous [preservative free]:

Bridion: 500 mg/5 mL (5 mL)

Pharmacology

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/Pharmacodynamics

Distribution

V_d: 11 to 14 L

Metabolism

Not metabolized

Excretion

Urine (95% as unchanged drug)

Onset of Action

<3 minutes

Half-Life Elimination

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

Protein Binding

Negligible

Use: Labeled Indications

Reversal of rocuronium or vecuronium: Reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults undergoing surgery

Contraindications

Hypersensitivity to sugammadex or any component of the formulation

Dosage and Administration

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: IV:

Deep block (at least 1 to 2 post-tetanic counts but prior to appearance of T₂): 4 mg/kg as a single dose

Moderate block (after appearance of T₂): 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 may be required.

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 may be required.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Routine reversal of rocuronium-induced moderate blockade: Limited data available: Infants, Children, and Adolescents: For age <2 years, the data is very limited: IV: 2 mg/kg as a single dose (Bridion prescribing information [European Medicines Agency] 2015; Plaud 2009). Dosing based on multicenter, randomized, parallel-group, dose-finding study in pediatric (n=63; age range: 28 days to 17 years) and adult (n=28) surgical patients. Results showed sugammadex was well tolerated in all ages studied and a dose response relation was shown for children ≥2 years, adolescents, and adults when administered at reappearance of T₂ for reversal of rocuronium-induced moderate neuromuscular blockade. Although similar recovery times were seen in infants and children <2 years, a dose response relationship could not be determined due to the small number enrolled (n=8). Median time to recovery in all groups was 1.1 to 1.2 minutes after 2 mg/kg dose (Plaud 2009).

Administration

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.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. When not protected from light, use vial within 5 days.

Drug Interactions

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

Estrogen Derivatives (Contraceptive): Sugammadex may decrease the serum concentration of Estrogen Derivatives (Contraceptive). 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. Consider therapy modification

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

Progestins (Contraceptive): Sugammadex may decrease the serum concentration of Progestins (Contraceptive). 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. Consider therapy modification

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

Test Interactions

May interfere with the serum progesterone assay; interaction may be observed for up to 30 minutes after a 16 mg/kg dose of sugammadex.

Adverse Reactions

>10%:

Cardiovascular: Hypotension (5% to 13%)

Central nervous system: Headache (10%)

Gastrointestinal: Nausea (26%), vomiting (11% to 15%)

Local: Pain at injection site (48% to 52%)

1% to 10%:

Cardiovascular: Hypertension (9%), prolonged QT interval on ECG (6%), bradycardia (5%), tachycardia (2% to 5%)

Central nervous system: Anesthesia complication (1% to 9%), chills (7%), incisional pain (4% to 6%), dizziness (3% to 6%), insomnia (5%), hypoesthesia (3%), anxiety (1% to 3%), restlessness (1% to 2%), depression (≤2%)

Dermatologic: Pruritus (3%), erythema (2%)

Endocrine & metabolic: Hypocalcemia (2%)

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

Hematologic & oncologic: Wound hemorrhage (2%), decreased red blood cells (1% to 2%)

Neuromuscular & skeletal: Limb pain (6%), musculoskeletal pain (2%), myalgia (2%), increased creatine phosphokinase (1% to 2%), neuromuscular blockade (≤2%; reoccurrence)

Respiratory: Cough (3% to 8%)

Miscellaneous: Fever (5% to 9%), procedural complications (8%), hysterectomy (2%)

<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylactoid reaction, anaphylaxis, atrial fibrillation, atrioventricular block, bronchospasm, dyspnea, extrasystoles, hypersensitivity reaction, laryngospasm, pulmonary edema, ST segment changes on ECG, supraventricular extrasystole, supraventricular tachycardia, urticaria, ventricular fibrillation, ventricular tachycardia, wheezing

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

Neuromuscular stimulation (eg, post-tetanic counts [PTC] and train-of-four [TOF]); 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)

Pregnancy

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). 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.

Patient Education

What is this drug used for?

• It is used to reverse the effects of some drugs.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Abdominal pain
• Painful extremities
• Cough
• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop.
• Flushing
• Skin irritation
• Fast heartbeat
• Slow heartbeat
• Abnormal heartbeat
• Chest pain
• Severe dizziness
• Passing out
• Severe headache
• Sore throat
• Mouth irritation
• Vision changes
• Chills
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.