sugammadex
Injection, Solution · Intravenous
Uses
Sugammadex Injection is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adult and pediatric patients aged 2 years and older undergoing surgery. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's BRIDION ® (sugammadex) injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that information. Sugammadex Injection is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adult and pediatric patients aged 2 years and older undergoing surgery. (1)
Dosage and administration
Dosing is based on actual body weight (2.1) Monitor for twitch responses to determine the timing and dose for Sugammadex Injection administration. (2.1) Administer as a single bolus injection. (2.1) For rocuronium and vecuronium: 4 mg/kg is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to train-of-four (TOF) stimulation. (2.2) 2 mg/kg is recommended if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation. (2.2) For rocuronium only: 16 mg/kg is recommended if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single dose of 1.2 mg/kg of rocuronium. Immediate reversal in pediatric patients has not been studied. (2.2) 2.1 Important Dosing and Administration Information Sugammadex Injection dosing is based on actual body weight. Sugammadex Injection, for intravenous use, should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents. Doses and timing of Sugammadex Injection administration should be based on monitoring for twitch responses and the extent of spontaneous recovery that has occurred. Administer Sugammadex Injection intravenously as a single bolus injection. The bolus injection may be given over 10 seconds, into an existing intravenous line. Sugammadex Injection has only been administered as a single bolus injection in clinical trials. From the time of Sugammadex Injection administration until complete recovery of neuromuscular function, monitor the patient to assure adequate ventilation and maintenance of a patent airway. Satisfactory recovery should be determined through assessment of skeletal muscle tone and respiratory measurements in addition to the response to peripheral nerve stimulation. The recommended dose of Sugammadex Injection does not depend on the anesthetic regimen. Preparation of dilution for pediatric use: Sugammadex Injection 100 mg/mL may be diluted to a concentration of 10 mg/mL, using 0.9% sodium chloride injection, USP, to increase the accuracy of dosing in the pediatric population. To prepare the required dose, aseptically transfer all the contents of the 2 mL vial of Sugammadex Injection 2-mL single-dose vials containing 200 mg sugammadex (100 mg/mL) to a bottle (or intravenous bag) containing 18 mL of 0.9% sodium chloride injection, to achieve a final concentration of 10 mg/mL sugammadex. The diluted solution should be used immediately. Sugammadex Injection is a single-dose sterile solution without preservatives. Discard any unused portion from the vial. 2.2 Recommended Dosing Sugammadex Injection can be used to reverse different levels of rocuronium- or vecuronium-induced neuromuscular blockade. For rocuronium and vecuronium: A dose of 4 mg/kg Sugammadex Injection is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to train-of-four (TOF) stimulation following rocuronium-or vecuronium-induced neuromuscular blockade [see Warnings and Precautions (5.8)]. A dose of 2 mg/kg Sugammadex Injection is recommended if spontaneous recovery has reached the reappearance of the second twitch (T 2 ) in response to TOF stimulation following rocuronium-or vecuronium-induced neuromuscular blockade [see Warnings and Precautions (5.8)]. For rocuronium only: A dose of 16 mg/kg Sugammadex Injection is recommended if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single dose of 1.2 mg/kg of rocuronium. The efficacy of the 16 mg/kg dose of Sugammadex Injection following administration of vecuronium has not been studied. Immediate reversal in pediatric patients has not been studied [see Clinical Studies (14.1)]. 2.3 Drug Compatibility May inject Sugammadex Injection into the intravenous line of a running infusion with the following intravenous solutions: 0.9% sodium chloride 5% dextrose 0.45% sodium chloride and 2.5% dextrose 5% dextrose in 0.9% sodium chloride isolyte P with 5% dextrose Ringer's lactate solution Ringer's solution Ensure the infusion line is adequately flushed (e.g., with 0.9% sodium chloride) between administration of Sugammadex Injection and other drugs. Do not mix Sugammadex Injection with other products except those listed above. Sugammadex Injection is physically incompatible with verapamil, ondansetron, and ranitidine. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever the solution and container permit.
Dosage forms and strengths
Sugammadex Injection is a sterile, clear, colorless to slightly yellow-brown, non-pyrogenic aqueous solution intended for intravenous infusion. Sugammadex Injection 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)
Contraindications
Sugammadex Injection 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)
Warnings and precautions
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 Sugammadex Injection 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 Sugammadex Injection, waiting times should be based on the dose of Sugammadex Injection 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 Sugammadex Injection. The nature and frequency of anaphylaxis and hypersensitivity associated with Sugammadex Injection 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 Sugammadex Injection 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 Sugammadex Injection was 0.3% (n=1 in the Sugammadex Injection 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 Sugammadex Injection [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 Sugammadex Injection 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 Sugammadex Injection [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 Sugammadex Injection A minimum waiting time is necessary before administration of a steroidal neuromuscular blocking agent after administration of Sugammadex Injection. Table 1: Re-administration of Rocuronium or Vecuronium after Reversal (up to 4 mg/kg Sugammadex Injection) 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 Sugammadex Injection, 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 Sugammadex Injection 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 Sugammadex Injection, 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 .
Side effects
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 Sugammadex Injection 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 Sugammadex Injection doses of 2 or 4 mg/kg) were pain, vomiting, and nausea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 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 Sugammadex Injection 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 Sugammadex Injection 2 mg/kg or 4 mg/kg. Adverse reactions reported in ≥10% of patients at a 2, 4, or 16 mg/kg Sugammadex Injection 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 Sugammadex Injection 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* 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 * 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 Pediatric Patients 2 to <17 years of age The safety of Sugammadex Injection has been assessed in a randomized, active-controlled study of pediatric patients 2 to <17 years of age, with 242 receiving treatment with Sugammadex Injection. Adverse events occurring in ≥5% of pediatric patients are presented in Table 3. The safety profile was generally consistent with that observed in adults.
Drug interactions
Toremifene : Concomitant use can delay recovery. (7.2) Hormonal contraceptives : Patients must use an additional, non-hormonal method of contraception for 7 days following Sugammadex Injection administration. (5.6, 7.3) 7.1 Summary The information reported in sections 7.2 – 7.4 is based on binding affinity between Sugammadex Injection 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 Sugammadex Injection 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 Sugammadex Injection 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 Sugammadex Injection may bind to progestogen, thereby decreasing progestogen exposure. Therefore, the administration of a bolus dose of Sugammadex Injection 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 Sugammadex Injection 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 Sugammadex Injection 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.
Use in specific populations
Severe Renal Impairment : Not recommended. (8.6) Additional pediatric use information is approved for Merck Sharp & Dohme LLC's BRIDION ® (sugammadex) injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that information. 8.1 Pregnancy Risk Summary There are no clinical trial data on Sugammadex Injection use in pregnant women to inform any drug-associated risks. The available data from the pharmacovigilance safety database and published literature on Sugammadex Injection 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 Sugammadex Injection and any potential adverse effects on the breastfed infant from Sugammadex Injection 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 Sugammadex Injection, 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 Sugammadex Injection administration [see Drug Interactions (7.3)] . 8.4 Pediatric Use The safety and effectiveness of Sugammadex Injection 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 Sugammadex Injection in these age groups is supported by evidence from adequate and well-controlled studies of Sugammadex Injection [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.
Pregnancy
8.1 Pregnancy Risk Summary There are no clinical trial data on Sugammadex Injection use in pregnant women to inform any drug-associated risks. The available data from the pharmacovigilance safety database and published literature on Sugammadex Injection 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.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Sugammadex Injection 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 Sugammadex Injection in these age groups is supported by evidence from adequate and well-controlled studies of Sugammadex Injection [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. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's BRIDION® (sugammadex) injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that information.
Geriatric use
8.5 Geriatric Use Sugammadex Injection 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 Sugammadex Injection 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 Sugammadex Injection 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)] .
Overdosage
In premarketing clinical trials, one case of accidental overdose with 40 mg/kg Sugammadex Injection was reported without significant effects. Sugammadex Injection can be removed using hemodialysis with a high-flux filter, but not with a low-flux filter. Based upon clinical studies, Sugammadex Injection concentrations in plasma are reduced with a high-flux filter by about 70% after a 3- to 6-hour dialysis session.
Description
Sugammadex Injection, for intravenous use, contains sugammadex sodium, a modified gamma cyclodextrin chemically designated as 6 A ,6 B ,6 C ,6 D ,6 E ,6 F ,6 G ,6 H -Octakis-S-(2-carboxyethyl)- 6 A ,6 B ,6 C ,6 D ,6 E ,6 F ,6 G ,6 H -octathio-γ-cyclodextrin sodium salt (1:8) with a molecular weight of 2178.01. The structural formula is: Sugammadex Injection is supplied as a sterile, non-pyrogenic aqueous solution that is clear, colorless to slightly yellow-brown for intravenous injection only. Each mL contains 100 mg sugammadex, which is equivalent to 108.8 mg sugammadex sodium. The aqueous solution is adjusted to a pH of between 7 and 8 with hydrochloric acid and/or sodium hydroxide. The osmolality of the product is between 300 and 500 mOsmol/kg. Sugammadex Injection may contain up to 7 mg/mL of the mono OH-derivative of sugammadex [see Clinical Pharmacology (12.2)] . This derivative is chemically designated as 6 A ,6 B ,6 C ,6 D ,6 E ,6 F ,6 G -Heptakis-S-(2- carboxyethyl)-6 A ,6 B ,6 C ,6 D ,6 E ,6 F ,6 G -heptathio-γ-cyclodextrin sodium salt (1:7) with a molecular weight of 2067.90. The structural formula is: Image Image
Mechanism of action
12.1 Mechanism of Action Sugammadex Injection 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.
How supplied
Sugammadex Injection is a clear, colorless to slightly yellow-brown, non-pyrogenic aqueous solution intended for intravenous infusion. Sugammadex Injection is available in the following presentations: Sugammadex Injection 2-mL single-dose vials containing 200 mg sugammadex (100 mg/mL) Box of 10 NDC 70069-892-10 Sugammadex Injection 5-mL single-dose vials containing 500 mg sugammadex (100 mg/mL) Box of 10 NDC 70069-893-10 The packaging of this product is not made with natural rubber latex. Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). Protect from light. When not protected from light, the vial should be used within 5 days. Discard unused portion.
Patient information
Advise females of reproductive potential using hormonal contraceptives that Sugammadex Injection may reduce the contraceptive effect . Instruct females to use an additional, non-hormonal method of contraception for the next 7 days following Sugammadex Injection administration [see Drug Interactions (7.3)].
Label text from the FDA structured product label by Solupharm Pharmazeutische Erzeugnisse GmbH (revised Aug 20, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Sugammadex Sodium in 34 products
sugammadex NDC products (34)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 16729-726 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Accord Healthcare Inc. | ANDA |
| 16729-727 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Accord Healthcare Inc. | ANDA |
| 0264-8200 | Sugammadex Sodium 200 mg/2mL Injection | B. Braun Medical Inc. | ANDA |
| 31722-254 | Sugammadex Sodium 100 mg/mL Injection | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-255 | Sugammadex Sodium 100 mg/mL Injection, Solution | Camber Pharmaceuticals, Inc. | ANDA |
| 43598-924 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Dr. Reddy's Laboratories Inc. | ANDA |
| 43598-925 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Dr. Reddy's Laboratories Inc. | ANDA |
| 72266-269 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Fosun Pharma USA Inc. | ANDA |
| 72266-268 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Fosun Pharma USA Inc. | ANDA |
| 76045-219 | Sugammadex Sodium 100 mg/mL Injection, Solution | Fresenius Kabi USA, LLC | ANDA |
| 68083-442 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Gland Pharma Limited | ANDA |
| 68083-441 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Gland Pharma Limited | ANDA |
| 68462-695 | Sugammadex Sodium 200 mg/2mL Injection, Solution | GLENMARK PHARMACEUTICALS INC., USA | ANDA |
| 68462-696 | Sugammadex Sodium 500 mg/5mL Injection, Solution | GLENMARK PHARMACEUTICALS INC., USA | ANDA |
| 0641-6270 | Sugammadex Sodium 100 mg/mL Injection | Hikma Pharmaceuticals USA Inc. | ANDA |
| 70748-370 | Sugammadex Sodium 100 mg/mL Injection, Solution | Lupin Pharmaceuticals, Inc. | ANDA |
| 70748-371 | Sugammadex Sodium 100 mg/mL Injection, Solution | Lupin Pharmaceuticals, Inc. | ANDA |
| 71872-7382 | Sugammadex Sodium 100 mg/mL Injection, Solution | Medical Purchasing Solutions, LLC | ANDA |
| 67457-969 | Sugammadex Sodium 100 mg/mL Injection, Solution | Mylan Institutional LLC | ANDA |
| 67457-970 | Sugammadex Sodium 100 mg/mL Injection, Solution | Mylan Institutional LLC | ANDA |
| 72205-478 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-479 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Novadoz Pharmaceuticals LLC | ANDA |
| 25021-619 | Sugammadex Sodium 100 mg/mL Injection, Solution | Sagent Pharmaceuticals | ANDA |
| 0781-3469 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Sandoz Inc | ANDA |
| 0781-3468 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Sandoz Inc | ANDA |
| 55579-893 | Sugammadex Sodium 100 mg/mL Injection, Solution | Solupharm Pharmazeutische Erzeugnisse GmbH | ANDA |
| 55579-892 | Sugammadex Sodium 100 mg/mL Injection, Solution | Solupharm Pharmazeutische Erzeugnisse GmbH | ANDA |
| 70069-893 | Sugammadex Sodium 100 mg/mL Injection, Solution | Somerset Therapeutics, LLC | ANDA |
| 70069-892 | Sugammadex Sodium 100 mg/mL Injection, Solution | Somerset Therapeutics, LLC | ANDA |
| 62756-079 | Sugammadex Sodium 100 mg/mL Injection, Solution | Sun Pharmaceutical Industries, Inc. | ANDA |
| 70771-1857 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Zydus Lifesciences Limited | ANDA |
| 70771-1856 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Zydus Lifesciences Limited | ANDA |
| 70710-1651 | Sugammadex Sodium 500 mg/5mL Injection, Solution | Zydus Pharmaceuticals USA Inc. | ANDA |
| 70710-1650 | Sugammadex Sodium 200 mg/2mL Injection, Solution | Zydus Pharmaceuticals USA Inc. | ANDA |
Frequently asked questions
What is sugammadex used for?
Sugammadex Injection is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adult and pediatric patients aged 2 years and older undergoing surgery. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's BRIDION ® (sugammadex) injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug…
What are the side effects of sugammadex?
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 Sugammadex Injection dose and higher than the placebo rate): vomiting, pain,… See the full label for the complete list.
Who makes sugammadex?
sugammadex is listed by 20 labelers in the FDA NDC directory, including Accord Healthcare Inc., B. Braun Medical Inc., Camber Pharmaceuticals, Inc., Dr. Reddy's Laboratories Inc..