Sugammadex is a modified gamma cyclodextrin for the reversal of neuromuscular blockade effects of rocuronium and vecuronium in adults and pediatric patients 2 years and older undergoing surgery. Sugammadex use for reversal of neuromuscular blockade in the intensive care unit or for reversal of nonsteroidal neuromuscular blocking agents or steroidal neuromuscular blocking agents other than rocuronium and vecuronium has not been studied. Cases of marked bradycardia, some resulting in cardiac arrest, have been observed within minutes of sugammadex administration; monitor hemodynamic parameters for changes during and after sugammadex receipt.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Sugammadex is a clear, colorless to slightly yellow-brown solution.
-Sugammadex should be administered by health care providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents and drugs that reverse neuromuscular blockade.
-Do not mix sugammadex with any other medications.
-Sugammadex is physically incompatible with verapamil, ondansetron, and ranitidine.
Intravenous Administration
Preparation in Adult patients
-May administer undiluted solution; no further dilution is necessary.
Preparation in Pediatric patients
-May administer undiluted solution; no further dilution is necessary.
-To increase the accuracy of dosing in the pediatric population, sugammadex 100 mg/mL may be diluted to a concentration of 10 mg/mL using 0.9% Sodium Chloride Injection.
--To prepare the required dose, aseptically transfer all the contents of the 2 mL single-dose vial containing 200 mg sugammadex (100 mg/mL) to a bottle (or IV bag) containing 18 mL of 0.9% Sodium Chloride Injection to achieve a final concentration of 10 mg/mL sugammadex.
-Sugammadex injection is a single-dose sterile solution without preservatives; discard any unused portion from the vial.
-Storage: Use diluted solution immediately.
IV Push
-Infuse over 10 seconds as a single bolus injection into an existing intravenous line.
-Sugammadex may be injected into intravenous lines of a running infusion of 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 0.45% Sodium Chloride and 2.5% Dextrose Injection, 5% Dextrose in 0.9% Sodium Chloride Injection, Isolyte P with 5% Dextrose Injection, Lactated Ringer's Injection, or Ringer's Injection.
-Flush the infusion line between administration of sugammadex and other drugs.
-Monitor the patient to assure adequate ventilation and maintenance of patent airway from time of sugammadex administration until complete recovery of neuromuscular function. Satisfactory recovery should be determined by response to peripheral nerve stimulation and assessment of skeletal muscle tone and respiratory measurements.
Overall, procedural complications were reported in 1%, 1%, 8%, and 1% of sugammadex 2 mg/kg, 4 mg/kg, 16 mg/kg, and placebo groups, respectively, in adult clinical trials. Airway complication of anesthesia and anesthetic complication were reported in 9% of those receiving sugammadex 16 mg/kg compared to 1% of those in the 2 mg/kg and 4 mg/kg groups and in less than 1% of those receiving placebo. Incision site pain was reported in 4% to 6% of sugammadex patients vs. 1% in the placebo group. General pain and/or procedural pain was reported in 36% to 52% of those receiving sugammadex and in 38% of those in the placebo group. Recurrence of neuromuscular blockade was reported in no patients receiving sugammadex 2 mg/kg or placebo, in less than 1% of patients receiving sugammadex 4 mg/kg, and in 2% of those receiving sugammadex 16 mg/kg.
Hypersensitivity reactions, including anaphylactoid reactions, were reported in adult clinical trials and in postmarketing reports and have occurred in patients with no previous exposure to sugammadex. Symptoms associated with hypersensitivity include flushing, urticaria, erythematous rash, severe low blood pressure, fast heart rate, angioedema, pharyngeal edema, bronchospasm, and pulmonary obstructive events. Serious hypersensitivity reactions can be fatal. Among 375 healthy volunteers who received placebo or sugammadex (4 mg/kg IV or 16 mg/kg IV) in a trial evaluating hypersensitivity reactions, hypersensitivity was reported in 1%, 7%, and 9% in the placebo, sugammadex 4 mg/kg, and sugammadex 16 mg/kg groups, respectively. Anaphylaxis was not reported in the placebo or lower dose sugammadex group but was reported in 1 patient (0.3%) receiving sugammadex 16 mg/kg. There was no evidence of increased frequency or severity of hypersensitivity with repeat dosing. Among 298 healthy subjects in a similar trial, anaphylaxis was reported in 1% of patients receiving sugammadex 16 mg/kg. Pruritus was reported in 2% to 3% of patients receiving sugammadex compared to 2% of those receiving placebo. Erythema was reported in 0% to 2% of patients receiving sugammadex compared to 1% of those in the placebo group. Bronchospasm has been reported as a possibly related adverse reaction in a clinical trial and postmarketing data in patients with a history of pulmonary complications.
Monitor patients closely for hemodynamic changes during and after sugammadex administration. Bradycardia was reported in 1% of sugammadex-treated patients receiving 2 mg/kg and 4 mg/kg and in 5% of those in the 16 mg/kg group in adult clinical trials. Bradycardia was reported in 7% to 10% of pediatric patients receiving sugammadex during clinical trials (n = 242). Cases of marked bradycardia, some resulting in cardiac arrest, have been observed within minutes of sugammadex administration. Administer anticholinergic agents (e.g., atropine) if clinically significant bradycardia occurs. Sinus tachycardia was also reported in 2% to 5% of sugammadex-treated adult patients in clinical trials. Both hypertension and hypotension can also occur with the administration of sugammadex. In adult clinical trials, hypertension (5% to 9%) and hypotension (4% to 13%) were reported in sugammadex-treated patients. Atrial fibrillation, AV block, cardiac arrest, ST segment changes, supraventricular tachycardia (SVT) and/or extrasystoles, ventricular tachycardia, and ventricular fibrillation have been reported with the postmarketing use of sugammadex. Anaphylaxis associated with ECG ST segment changes (elevation or depression) consistent with acute myocardial ischemia or coronary spasm has also been reported.
Psychiatric adverse reactions have been reported with the use of sugammadex. In adult clinical trials, anxiety was reported in 1% to 3% of sugammadex patients compared to less than 1% of those in the placebo group. Restlessness was reported in 2% or less of patients receiving sugammadex vs. less than 1% of patients in the placebo group. Depression was reported in 2% or less in the sugammadex groups compared to no patients receiving placebo. Insomnia was reported in 2% to 5% of patients receiving sugammadex compared to 4% of those in the placebo group.
During adult clinical trials, hypocalcemia was reported in 1% to 2% of patients receiving sugammadex compared to 1% of patients receiving placebo.
Musculoskeletal pain and myalgia were reported in 1% to 2% of patients receiving sugammadex and in 1% receiving placebo in adult clinical trials. Pain in the extremity was reported in 1%, 2%, 6%, and 3% in the sugammadex 2 mg/kg, 4 mg/kg, 16 mg/kg, and placebo groups respectively. Increased blood creatinine phosphokinase was reported in 1% to 2% of sugammadex patients vs. less than 1% of patients receiving placebo.
In adult clinical trials, cough was reported in 1% of those receiving 2 mg/kg sugammadex, 3% of those in the 4 mg/kg group, and in 8% of those receiving 16 mg/kg compared to 2% of those in the placebo group. Oropharyngeal pain (throat irritation) was reported in 5% of those in the 2 mg/kg and 16 mg/kg groups, 3% of those receiving 4 mg/kg, and in 5% of those in the placebo group.
Gastrointestinal adverse reactions, including nausea (23% to 26%), vomiting (11% to 15%), abdominal pain (4% to 6%), flatulence (1% to 3%), and xerostomia (dry mouth; 2% or less), were reported during sugammadex adult clinical trials. Nausea (2% to 8%) and vomiting (3% to 10%) were reported in pediatric patients receiving sugammadex during clinical trials (n = 242).
In adult clinical trials, fever was reported in 9% of patients receiving sugammadex 2 mg/kg, 6% of those receiving 4 mg/kg, and in 5% of those in the 16 mg/kg group compared to 3% of those receiving placebo. Chills were reported in 3% of those receiving 2 mg/kg and 4 mg/kg and in 7% of those in the 16 mg/kg group compared to 5% of those receiving placebo.
Sugammadex is associated with increases in coagulation parameters. In adult patients undergoing major orthopedic surgery of lower extremity who were also receiving heparin or low molecular weight heparin for thromboprophylaxis, increases in activated partial thromboplastin time (aPTT) and prothrombin time/international normalized ratio (PT[INR]) of 5.5% and 3%, respectively, were reported in the hour after sugammadex 4 mg/kg administration. An increase in blood loss or anemia was not reported. The rate of bleeding events within 24 hours was 2.9% for those receiving sugammadex and 4.1% for those receiving usual care. Post-operative anemia was reported in 21% of those who received sugammadex compared to 22% of those receiving usual care. The mean 24-hour drainage volume (0.46 L sugammadex vs. 0.48 L usual care) and post-operative transfusion rates (37% sugammadex vs. 39% usual care) were similar between the sugammadex group and those receiving usual care. In sugammadex adult clinical trials, wound bleeding was reported in 0% to 2% of those receiving sugammadex and 1% of those in the placebo group. Decreases in red blood cell count, hemoglobin, or hematocrit were reported in 1% to 2% of sugammadex patients compared to less than 1% of those receiving placebo.
Abnormalities in the QT interval, including QT prolongation, were reported in sugammadex adult clinical trials. Among those receiving sugammadex 2 mg/kg, 4 mg/kg, and 16 mg/kg, QT abnormalities were reported in 1%, less than 1%, and 6% of patients, respectively, compared to 1% of those receiving placebo.
Laryngospasm, dyspnea, wheezing, pulmonary edema, and respiratory arrest have been reported with the postmarketing use of sugammadex.
Adverse reactions affecting the central nervous system have been reported with the use of sugammadex. During adult clinical trials, headache was reported in 7% of those receiving sugammadex 2 mg/kg, 5% receiving 4 mg/kg, and 10% receiving 16 mg/kg as compared to 8% of those receiving placebo. Dizziness was reported in 5% of patients receiving sugammadex 2 mg/kg, 3% receiving 4 mg/kg, 6% receiving 16 mg/kg and in 2% of those in the placebo group. Hypoesthesia was reported in 1% to 3% of sugammadex patients compared to 2% of those receiving placebo. In pediatric clinical trials, nonspecific eye disorders were reported in 1% to 6% of patients receiving sugammadex 2 mg/kg or 4 mg/kg doses (n = 242).
During clinical trials where neuromuscular blockade was reversed with sugammadex intentionally in the middle of anesthesia, signs of light anesthesia (e.g., movement, coughing, grimacing, and suckling of the endotracheal tube) were observed.
Cases of marked bradycardia, some resulting in cardiac arrest, have been observed within minutes of sugammadex administration. Monitor patients closely for hemodynamic changes during and after neuromuscular blockade reversal. Consider administering atropine if clinically significant bradycardia occurs.
Ventilatory support is mandatory for all patients until spontaneous respiration is restored and the the ability to maintain a patent airway is assured. Other drugs used in the peri- and post-operative setting could cause respiratory depression; therefore, ventilatory support may be required even after recovery from neuromuscular blockade is complete. In clinical trials, a delayed or minimal response to sugammadex was reported in a small number of patients. Take appropriate actions to provide adequate ventilation if neuromuscular blockade persists after sugammadex administration or following extubation.
Sugammadex doses of up to 16 mg/kg have been associated with increases in activated partial thromboplastin time (aPTT) and prothrombin time/international normalized ratio [PT(INR)] of up to 25% for up to 1 hour in healthy volunteers. In patients receiving heparin and low molecular weight heparin and undergoing major orthopedic surgery of lower extremity, aPTT and PT(INR) were increased by 5.5% and 3%, respectively, in the hour following sugammadex 4 mg/kg administration. Increased bleeding or anemia was not observed with sugammadex compared to usual treatment. Carefully monitor coagulation parameters in patients with known coagulopathy, being treated with therapeutic anticoagulation, receiving thromboprophylaxis drugs other than heparin and low molecular weight heparin, or receiving thromboprophylaxis and who also receive sugammadex 16 mg/kg.
Neuromuscular blockade recurrence may occur after the administration of sugammadex due to displacement of rocuronium or vecuronium from sugammadex by other drugs. If this occurs, the patient may require mechanical ventilation, and any infusion of the drug that caused displacement should be stopped. The risk of displacement reactions is highest in the time period equivalent to 3 times the half-life of sugammadex. Neuromuscular blockade recurrence may also occur when drugs that potentiate neuromuscular blockade are administered in the post-operative setting with mechanical ventilation possibly being required as well. Furthermore, neuromuscular blockade recurrence after initial reversal also could occur when using lower than recommended sugammadex doses; follow product label dosing recommendations.
The use of sugammadex in patients with severe renal impairment (i.e., CrCl less than 30 mL/minute, including dialysis dependence) is not recommended due to insufficient safety information in addition to prolonged and increased exposure in these patients. Recommended waiting times between the administration of sugammadex and readministration of rocuronium or vecuronium are extended in patients with mild or moderate renal impairment.
The mean time to recovery from neuromuscular blockade is slightly longer in the geriatric population compared to younger patients, but no dose adjustment is necessary in geriatric patients with normal organ function. Sugammadex is substantially excreted by the kidney. The risk of adverse reactions may be higher in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, the sugammadex dose should be carefully selected, and renal function monitoring may be useful.
There are no clinical trial data with sugammadex use during pregnancy to inform a drug-associated risk. Data from the pharmacovigilance safety database and published literature on sugammadex use in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of malformations after 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; maternal toxicity was also observed.
There are no data on the presence of sugammadex in human milk, the effects on the breast-fed infant, or the effects on milk production. However, sugammadex is present in rat milk. Consider the benefits of breast-feeding along with the mother's clinical need for sugammadex and any potential adverse effects on the breast-fed infant from sugammadex or the underlying maternal condition.
General Dosing Information
-The use of sugammadex for reversal of neuromuscular blockade following rocuronium or vecuronium administration in the intensive care unit has not been studied.
-Do not use sugammadex for reversal of neuromuscular blockade following nonsteroidal neuromuscular blocking agents (e.g., succinylcholine) or steroidal neuromuscular blocking agents other than rocuronium or vecuronium.
For neuromuscular blockade reversal of rocuronium or vecuronium in patients undergoing surgery:
-for the reversal of neuromuscular blockade induced by rocuronium:
Intravenous dosage:
Adults: 2, 4, or 16 mg/kg IV as a single dose to reverse different levels of rocuronium-induced neuromuscular blockade. 2 mg/kg IV as a single dose if spontaneous recovery has reached the reappearance of the second twitch (T2) in response to train-of-four (TOF) stimulation. 4 mg/kg IV as a single dose if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to TOF stimulation. 16 mg/kg IV as a single dose if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single rocuronium dose of 1.2 mg/kg. For re-use of rocuronium after sugammadex (up to 4 mg/kg/dose) administration, wait at least 5 minutes before readministration of rocuronium 1.2 mg/kg/dose and 4 hours before readministration of rocuronium 0.6 mg/kg/dose. The onset of neuromuscular blockade may be delayed up to 4 minutes, and the duration of blockade may be shortened up to 15 minutes after the readministration of rocuronium 1.2 mg/kg/dose within 30 minutes of sugammadex use. If a dose of sugammadex 16 mg/kg/dose was used for reversal, wait at least 24 hours before readministration of rocuronium. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocker. The onset of a depolarizing neuromuscular blocker might be slower than expected, as postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
Children and Adolescents 2 to 17 years: 2 or 4 mg/kg IV as a single dose to reverse different levels of rocuronium-induced neuromuscular blockade. 2 mg/kg IV as a single dose if spontaneous recovery has reached the reappearance of the second twitch (T2) in response to train-of-four (TOF) stimulation. 4 mg/kg IV as a single dose if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to TOF stimulation. For re-use of rocuronium after sugammadex (up to 4 mg/kg/dose) administration, wait at least 5 minutes before readministration of rocuronium 1.2 mg/kg/dose and 4 hours before readministration of rocuronium 0.6 mg/kg/dose. The onset of neuromuscular blockade may be delayed up to 4 minutes, and the duration of blockade may be shortened up to 15 minutes after the readministration of rocuronium 1.2 mg/kg/dose within 30 minutes of sugammadex use. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocker. The onset of a depolarizing neuromuscular blocker might be slower than expected, as postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
-for the reversal of neuromuscular blockade induced by vecuronium:
Intravenous dosage:
Adults: 2 or 4 mg/kg IV as a single dose to reverse different levels of vecuronium-induced neuromuscular blockade. 2 mg/kg IV as a single dose if spontaneous recovery has reached the reappearance of the second twitch (T2) in response to train-of-four (TOF) stimulation. 4 mg/kg IV as a single dose if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to TOF stimulation. For re-use of vecuronium after sugammadex (up to 4 mg/kg/dose) administration, wait at least 4 hours before readministration of vecuronium 0.1 mg/kg/dose. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocker. The onset of a depolarizing neuromuscular blocker might be slower than expected, as postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
Children and Adolescents 2 to 17 years: 2 or 4 mg/kg IV as a single dose to reverse different levels of vecuronium-induced neuromuscular blockade. 2 mg/kg IV as a single dose if spontaneous recovery has reached the reappearance of the second twitch (T2) in response to train-of-four (TOF) stimulation. 4 mg/kg IV as a single dose if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to TOF stimulation. For re-use of vecuronium after sugammadex (up to 4 mg/kg/dose) administration, wait at least 4 hours before readministration of vecuronium 0.1 mg/kg/dose. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocker. The onset of a depolarizing neuromuscular blocker might be slower than expected, as postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
Maximum Dosage Limits:
-Adults
16 mg/kg/dose IV.
-Geriatric
16 mg/kg/dose IV.
-Adolescents
4 mg/kg/dose IV.
-Children
2 to 12 years: 4 mg/kg/dose IV.
younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
CrCl 30 to 80 mL/minute: No dosage adjustments needed. The recommended waiting time after neuromuscular blockade reversal with sugammadex (up to 4 mg/kg/dose) prior to readministration of rocuronium 0.6 mg/kg/dose or vecuronium 0.1 mg/kg/dose is 24 hours. If a shorter waiting time is required, the rocuronium dose for new neuromuscular blockade should be 1.2 mg/kg/dose.
CrCl less than 30 mL/minute: Not recommended for use due to lack of safety data and the prolonged and increased exposure in this patient population.
*non-FDA-approved indication
Conjugated Estrogens; Medroxyprogesterone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Desogestrel; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Dienogest; Estradiol valerate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Drospirenone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Drospirenone; Estetrol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Drospirenone; Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Drospirenone; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Elagolix; Estradiol; Norethindrone acetate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Estradiol; Levonorgestrel: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Estradiol; Norethindrone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Estradiol; Norgestimate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Ethinyl Estradiol; Norelgestromin: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Ethinyl Estradiol; Norethindrone Acetate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Ethinyl Estradiol; Norgestrel: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Etonogestrel: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Etonogestrel; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Leuprolide; Norethindrone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Levonorgestrel: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Levonorgestrel; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Medroxyprogesterone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norethindrone: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norethindrone; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norgestimate; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Norgestrel: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Oral Contraceptives: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Relugolix; Estradiol; Norethindrone acetate: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Segesterone Acetate; Ethinyl Estradiol: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins.
Toremifene: (Minor) Toremifene has a relatively high binding affinity for sugammadex and could displace vecuronium or rocuronium from the complex with sugammadex. The recovery to train of four (TOF) ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of surgery.
Sugammadex is a modified gamma cyclodextrin that forms a complex with the neuromuscular blocking agents rocuronium and vecuronium. This results in a reduction in the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction, and the neuromuscular blockade induced by rocuronium or vecuronium is thereby reversed.
Sugammadex is administered intravenously. The observed steady-state Vd in adult patients with normal renal function is 11 to 14 L. Sugammadex and the complex of sugammadex and rocuronium do not bind to plasma proteins or erythrocytes. No metabolites of sugammadex have been observed in clinical studies and only renal excretion of the unchanged product was observed as the route of elimination. More than 90% of the dose is excreted within 24 hours with at least 95% as unchanged drug. The elimination half-life of sugammadex in adults is about 2 hours, and the estimated plasma clearance is about 88 mL/minute. Sugammadex was retained in sites of active mineralization, such as bone and teeth, with a mean half-life of 172 and 8 days, respectively, in animal studies.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
Linear kinetics are observed when sugammadex is administered within the dosage range of 1 to 16 mg/kg as an IV bolus.
-Special Populations
Renal Impairment
In adult patients with mild, moderate, and severe renal impairment, the half-life of sugammadex is prolonged to 4, 6, and 19 hours, respectively. In a clinical trial of adult patients with severe renal impairment, exposure was 17 times higher than that seen in patients with normal renal function, and low concentrations of sugammadex were detectable for at least 48 hours after administration. In a second study, sugammadex clearance progressively decreased and the half-life progressively increased with declining renal function. In adult patients with moderate and severe renal impairment, exposure was 2 and 5 times higher, respectively, than patients with normal renal function. Sugammadex concentrations were not detectable beyond 7 days post-dose in patients with severe renal impairment.
Pediatrics
Sugammadex exposure (AUC0-inf and Cmax) increased in a dose-dependent, linear manner after administration of intravenous doses of 2 and 4 mg/kg in pediatric patients 2 to 16 years of age. Sugammadex exposure was approximately 40% lower in patients 2 to 5 years of age compared to older pediatric patients (6 to 16 years of age) and adults; however, this difference was not clinically relevant. Both clearance and Vd increase with increasing age in pediatric patients. The observed steady-state Vd of sugammadex is approximately 3 to 10 L and clearance is approximately 38 to 95 mL/minute resulting in a half-life of approximately 1 to 2 hours in pediatric patients 2 to 16 years of age.
Geriatric
Beyond the effects of decreased creatinine clearance, age has limited influence on suggamadex pharmacokinetic parameters.
Gender Differences
No pharmacokinetic differences between males and females have been observed.
Ethnic Differences
No clinically relevant differences in sugammadex pharmacokinetics were observed between Japanese and Caucasian patients. Limited data do not indicate any differences in pharmacokinetic parameters in Black or African Americans.
Obesity
In a study of obese patients (body mass index of 40 kg/m2 or more), sugammadex 2 mg/kg and 4 mg/kg was dosed according to actual body weight (ABW, n = 76) or ideal body weight (IBW, n = 74). Sugammadex exposure increased in a dose-dependent, linear manner after administration according to ABW or IBW. No clinically relevant differences in pharmacokinetic parameters were observed between obese patients and the general population when dosed according to ABW. Systemic exposure of sugammadex is approximately 50% lower with IBW dosing compared to ABW. A trial of 188 obese patients (body mass index of 40 kg/m2 or more) investigated the time to recovery from moderate or deep neuromuscular blockade induced by rocuronium or vecuronium. Patients received sugammadex 2 or 4 mg/kg, as appropriate for level of block, dosed according to either ABW or 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 of 0.9 or more in patients dosed by ABW (1.8 minutes) was statistically significantly faster compared to patients dosed by IBW (3.3 minutes).