Clinical medicine profile
Sugammadex sodium
Therapeutic agent (verify pharmacological class)
- Route
- INTRAVENOUS
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- 4 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.
Precautions
- 5 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.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
• 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 Pre-filled syringe of sugammadex injection 2-mL single-dose pre-filled syringe 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 pre-filled Syringe. 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. 2.4 Instructions for the Use of Pre-filled Syringe CAUTION: Assure that the needle or Needleless Luer Access Device (NLAD) is securely attached before beginning the injection. Visually inspect the syringe-needle or syringe-NLAD connection before and during drug administration. Administration Technique 1. Remove glass syringe barrel from blister pack and check that it is not damaged. 2. Inspect visually for particulate matter and discoloration prior to administration. Do not use the solution if it is colored or cloudy, or if it contains particulate matter. Figure 1 3. Hold the syringe upright on the ribbed part (C). With the other hand, take hold of the cap (A) and carefully TWIST THE SYRINGE TIP CAP COUNTER-CLOCKWISE until the cap disconnects for removal (see Figure 2). Figure 2 4. Pull the cap (A) off in a straight upward direction. DO NOT TOUCH THE STERILE SYRINGE TIP (Luer-Lok) (B) (see Figure 3). Figure 3 5. Connect the syringe to an appropriate injection connection depending on the route of administration. 6. Depress plunger rod to deliver the required dose of medication. Ensure that pressure is maintained on the plunger rod during the entire administration. 7. Discard unused portion. NOTES: • All steps must be performed sequentially. • This product is for single dose only; discard unused portion. • Store the pre-filled syringe at room temperature and keep it away from light and heat. image description image description image description
See label paediatric section if present; otherwise use paediatric formulary — do not extrapolate adult doses.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- 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.
Adverse effects
- 6 ADVERSE REACTIONS 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 Steriscience at 1-888-278-1784 or www.steri-science.com 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 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.
- Table 3: Pediatric Patients with (2 to < 17 years of age) Adverse Events Incidence ≥5% in One or More Treatment Groups Up to 7 Days Post-Treatment Sugammadex 2 mg/kg Sugammadex 4 mg/kg n (%) n (%) Subjects in population 51 191 with one or more specific adverse events 40 (78) 143 (75) with no specific adverse events 11 (22) 48 (25) Cardiac disorders 5 (10) 16 (8) Bradycardia* 5 (10) 13 (7) Eye disorders 3 (6) 1 (1) Gastrointestinal disorders 8 (16) 35 (18) Nausea 1 (2) 12 (6) Vomiting 4 (8) 20 (10) Injury, poisoning and procedural complications 34 (67) 121 (63) Incision site pain 3 (6) 6 (3) Procedural nausea 4 (8) 9 (5) Procedural pain 30 (59) 111 (58) Procedural vomiting 3 (6) 5 (3) * Combines preferred terms of bradycardia and sinus bradycardia Every subject is counted a single time for each applicable row and column.
- A system organ class or specific adverse event appears in this table only if its incidence in one or more of the columns meets the incidence criterion in the table title, after rounding.
- Anaphylaxis and Hypersensitivity Hypersensitivity reactions, including anaphylaxis, have occurred in both premarketing clinical trials and in post-marketing spontaneous reports.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
Sugammadex injection is a modified gamma cyclodextrin.
Read complete mechanism
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.
Product-specific
Product-specific
INTRAVENOUS
are assumed to be the same for non-complex-bound and complex-bound sugammadex in anesthetized patients. Distribution The observed steady-state volume of distribution of sugammadex is approximately 11 to 14 liters in adult patients with normal renal function (based on conventional...
In clinical studies, no metabolites of sugammadex have been observed and only renal
of the unchanged product was observed as the route of elimination. Elimination In adult anesthetized patients with normal renal function, the elimination
of 172 and 8 days, respectively [see Use in Specific Populations (8.4), Nonclinical Toxicology (13.2)] .
Pregnancy, lactation & diet
• Severe Renal Impairment : Not recommended. (8.6) See 17 for PATIENT COUNSELING INFORMATION 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. 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. 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)] . 8.6 Renal Impairment This drug is known to be substantially excreted by the kidney. Effect of mild or moderate renal impairment (creatinine clearance ≥30 and ≤80 mL/min) on sugammadex PK and PD was obtained from a study in elderly patients [see Use in Specific Populations (8.5)] . Although clearance of drug decreased in elderly subjects with mild and moderate renal impairment, there was no significant difference in the ability of sugammadex to reverse the pharmacodynamic effect of rocuronium. Hence, no dosage adjustment is necessary for mild and moderate renal impairment. Sugammadex injection is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min) due to insufficient safety information combined with the prolonged and increased overall exposure in these patients [see Warnings and Precautions (5.11), Clinical Pharmacology (12.3)] . 8.7 Hepatic Impairment Sugammadex injection is not metabolized nor excreted by the liver; therefore, dedicated trials in patients with hepatic impairment have not been conducted. Exercise caution when administering Sugammadex injection to patients with hepatic impairment accompanied by coagulopathy or severe edema [see Warnings and Precautions (5.10, 5.14)] . 8.8 Cardiac Patients One trial of 76 patients who were diagnosed with or have a history of cardiac disease (e.g., patients with ischemic heart disease, chronic heart failure, or arrhythmia) of primarily NYHA (New York Heart Association) Class II investigated time to recovery from neuromuscular blockade induced by rocuronium 0.6 mg/kg following administration of 2 mg/kg or 4 mg/kg sugammadex injection given at the reappearance of T 2 . The trial showed that the median time to recovery of the T 4 /T 1 ratio to 0.9 was 1.7 minutes and 1.3 minutes, respectively, in the 2 mg/kg and 4 mg/kg sugammadex injection dose groups. This is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary [see Dosage and Administration (2.2)] . 8.9 Pulmonary Patients One trial of 77 patients who were diagnosed with or have a history of pulmonary complications investigated the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 mg/kg or 4 mg/kg sugammadex injection given at the first signs of recovery (reappearance of T 2 ). The trial showed that for these patients the median time to recovery of the T 4 /T 1 ratio to 0.9 was 2.1 minutes after a dose of 2 mg/kg sugammadex injection and 1.9 minutes after a dose of 4 mg/kg sugammadex injection. This is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary. [See Dosage and Administration (2.2), Adverse Reactions (6.1).] 8.10 Obese Patients with a BMI ≥ 40 kg/m 2 A trial of 188 obese patients, with a body mass index ≥40 kg/m 2 , investigated the time to recovery from moderate or deep neuromuscular blockade induced by rocuronium or vecuronium. Patients received 2 mg/kg or 4 mg/kg sugammadex injection, as appropriate for level of block, dosed according to either actual body weight (ABW) or ideal body weight (IBW) in random, double-blinded fashion. Pooled across depth of block and neuromuscular blocking agent, the median time to recover to a train-of-four (TOF) ratio ≥0.9 in patients dosed by…
• Severe Renal Impairment : Not recommended. (8.6) See 17 for PATIENT COUNSELING INFORMATION 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. 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. 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)] . 8.6 Renal Impairment This drug is known to be substantially excreted by the kidney. Effect of mild or moderate renal impairment (creatinine clearance ≥30 and ≤80 mL/min) on sugammadex PK and PD was obtained from a study in elderly patients [see Use in Specific Populations (8.5)] . Although clearance of drug decreased in elderly subjects with mild and moderate renal impairment, there was no significant difference in the ability of sugammadex to reverse the pharmacodynamic effect of rocuronium. Hence, no dosage adjustment is necessary for mild and moderate renal impairment. Sugammadex injection is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min) due to insufficient safety information combined with the prolonged and increased overall exposure in these patients [see Warnings and Precautions (5.11), Clinical Pharmacology (12.3)] . 8.7 Hepatic Impairment Sugammadex injection is not metabolized nor excreted by the liver; therefore, dedicated trials in patients with hepatic impairment have not been conducted. Exercise caution when administering Sugammadex injection to patients with hepatic impairment accompanied by coagulopathy or severe edema [see Warnings and Precautions (5.10, 5.14)] . 8.8 Cardiac Patients One trial of 76 patients who were diagnosed with or have a history of cardiac disease (e.g., patients with ischemic heart disease, chronic heart failure, or arrhythmia) of primarily NYHA (New York Heart Association) Class II investigated time to recovery from neuromuscular blockade induced by rocuronium 0.6 mg/kg following administration of 2 mg/kg or 4 mg/kg sugammadex injection given at the reappearance of T 2 . The trial showed that the median time to recovery of the T 4 /T 1 ratio to 0.9 was 1.7 minutes and 1.3 minutes, respectively, in the 2 mg/kg and 4 mg/kg sugammadex injection dose groups. This is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary [see Dosage and Administration (2.2)] . 8.9 Pulmonary Patients One trial of 77 patients who were diagnosed with or have a history of pulmonary complications investigated the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 mg/kg or 4 mg/kg sugammadex injection given at the first signs of recovery (reappearance of T 2 ). The trial showed that for these patients the median time to recovery of the T 4 /T 1 ratio to 0.9 was 2.1 minutes after a dose of 2 mg/kg sugammadex injection and 1.9 minutes after a dose of 4 mg/kg sugammadex injection. This is similar to the median values observed in the other trials; therefore, no dosage adjustment is necessary. [See Dosage and Administration (2.2), Adverse Reactions (6.1).] 8.10 Obese Patients with a BMI ≥ 40 kg/m 2 A trial of 188 obese patients, with a body mass index ≥40 kg/m 2 , investigated the time to recovery from moderate or deep neuromuscular blockade induced by rocuronium or vecuronium. Patients received 2 mg/kg or 4 mg/kg sugammadex injection, as appropriate for level of block, dosed according to either actual body weight (ABW) or ideal body weight (IBW) in random, double-blinded fashion. Pooled across depth of block and neuromuscular blocking agent, the median time to recover to a train-of-four (TOF) ratio ≥0.9 in patients dosed by…
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| No reviewed brand listings are linked yet. | |||
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.