Sugammasyn

Sugammadex (as sugammadex sodium).

Clear, slightly yellow solution, without visible particles.
Each 2 ml vial: Drug substance: Sugammadex (as sugammadex sodium) 200 mg.
Excipients/Inactive Ingredients: Sodium hydroxide 1M, hydrochloric acid 1M, water for injection, nitrogen.

Pharmacotherapeutic group: Antidotes. ATC code: V03AB35.
Pharmacology: Pharmacodynamics: Mechanism of action: Sugammadex is a modified gamma cyclodextrin which is a Selective Relaxant Binding Agent. It forms a complex with the neuromuscular blocking agents rocuronium or vecuronium in plasma and thereby reduces the amount of neuromuscular blocking agent available to bind to nicotinic receptors in the neuromuscular junction. This results in the reversal of neuromuscular blockade induced by rocuronium or vecuronium.
Pharmacodynamic effects: Sugammadex has been administered in doses ranging from 0.5 mg/kg to 16 mg/kg in dose response studies of rocuronium induced blockade (0.6, 0.9, 1.0 and 1.2 mg/kg rocuronium bromide with and without maintenance doses) and vecuronium induced blockade (0.1 mg/kg vecuronium bromide with or without maintenance doses) at different time points/depths of blockade. In these studies a clear dose-response relationship was observed.
Clinical efficacy and safety: Sugammadex can be administered at several time points after administration of rocuronium or vecuronium bromide: Routine reversal - deep neuromuscular blockade: In a pivotal study patients were randomly assigned to the rocuronium or vecuronium group. After the last dose of rocuronium or vecuronium, at 1-2 PTCs, 4 mg/kg sugammadex or 70 mcg/kg neostigmine was administered in a randomised order. The time from start of administration of sugammadex or neostigmine to recovery of the T₄/T₁ ratio to 0.9 was: Time (minutes) from administration of sugammadex or neostigmine at deep neuromuscular blockade (1-2 PTCs) after rocuronium or vecuronium to recovery of the T₄/T₁ ratio to 0.9. (See Table 1.)


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Routine reversal - moderate neuromuscular blockade: In another pivotal study patients were randomly assigned to the rocuronium or vecuronium group. After the last dose of rocuronium or vecuronium, at the reappearance of T₂, 2 mg/kg sugammadex or 50 mcg/kg neostigmine was administered in a randomised order. The time from start of administration of sugammadex or neostigmine to recovery of the T₄/T₁ ratio to 0.9 was: Time (minutes) from administration of sugammadex or neostigmine at reappearance of T₂ after rocuronium or vecuronium to recovery of the T₄/T₁ ratio to 0.9. (See Table 2.)


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Reversal by sugammadex of the neuromuscular blockade induced by rocuronium was compared to the reversal by neostigmine of the neuromuscular blockade induced by cis-atracurium. At the reappearance of T₂ a dose of 2 mg/kg sugammadex or 50 mcg/kg neostigmine was administered. Sugammadex provided faster reversal of neuromuscular blockade induced by rocuronium compared to neostigmine reversal of neuromuscular blockade induced by cis-atracurium: Time (minutes) from administration of sugammadex or neostigmine at reappearance of T₂ after rocuronium or cis-atracurium to recovery of the T₄/T₁ ratio to 0.9. (See Table 3.)


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For immediate reversal: The time to recovery from succinylcholine-induced neuromuscular blockade (1 mg/kg) was compared with sugammadex (16 mg/kg, 3 minutes later) - induced recovery from rocuronium-induced neuromuscular blockade (1.2 mg/kg). Time (minutes) from administration of rocuronium and sugammadex or succinylcholine to recovery of the T₁ 10%. (See Table 4.)


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In a pooled analysis the following recovery times for 16 mg/kg sugammadex after 1.2 mg/kg rocuronium bromide were reported: Time (minutes) from administration of sugammadex at 3 minutes after rocuronium to recovery of the T₄/T₁ ratio to 0.9, 0.8 or 0.7. (See Table 5.)


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Renal impairment: Two open label studies compared the efficacy and safety of sugammadex in surgical patients with and without severe renal impairment. In one study, sugammadex was administered following rocuronium induced blockade at 1-2 PTCs (4 mg/kg; N=68); in the other study, sugammadex was administered at reappearance of T₂ (2 mg/kg; N=30). Recovery from blockade was modestly longer for patients with severe renal impairment relative to patients without renal impairment. No residual neuromuscular blockade or recurrence of neuromuscular blockade was reported for patients with severe renal impairment in these studies.
Effects on QTc interval: In 3 dedicated clinical studies (N=287) with sugammadex alone, sugammadex in combination with rocuronium or vecuronium, and sugammadex in combination with propofol or sevoflurane were not associated with clinically significant prolongation of the QT/QTc interval. The integrated electrocardiogram and adverse event results of the Phase 2-3 studies support this conclusion.
Pharmacokinetics: The sugammadex pharmacokinetic parameters were calculated from the total sum of non-complex-bound and complex-bound concentrations of sugammadex. Pharmacokinetic parameters as clearance and volume of distribution are assumed to be the same for non-complex-bound and complex-bound sugammadex in anaesthetised subjects.
Distribution: The observed steady-state volume of distribution of sugammadex is approximately 11 to 14 litres in adult patients with normal renal function (based on conventional, non-compartmental pharmacokinetic analysis). Neither sugammadex nor the complex of sugammadex and rocuronium binds to plasma proteins or erythrocytes, as was shown in vitro using male human plasma and whole blood. Sugammadex exhibits linear kinetics in the dosage range of 1 to 16 mg/kg when administered as an IV bolus dose.
Metabolism: In preclinical and clinical studies no metabolites of sugammadex have been observed and only renal excretion of the unchanged product was observed as the route of elimination.
Elimination: In adult anaesthetised patients with normal renal function the elimination half-life (t_½) of sugammadex is about 1.8 hours and the estimated plasma clearance is about 88 mL/min. A mass balance study demonstrated that >90% of the dose was excreted within 24 hours. 96% of the dose was excreted in urine, of which at least 95% could be attributed to unchanged sugammadex. Excretion via faeces or expired air was less than 0.02% of the dose. Administration of sugammadex to healthy volunteers resulted in increased renal elimination of rocuronium in complex.
Special populations: Renal impairment and age: In two pharmacokinetic studies comparing patients with severe renal impairment to patients with normal renal function, plasma concentrations of sugammadex were similar for at least the first 20 minutes after dosing and then declined more rapidly than in controls. Total exposure to sugammadex was prolonged, resulting in approximately 15-fold higher exposure in patients with severe renal impairment. In some patients with severe renal impairment, sugammadex concentrations were minimally detectable in plasma after 1 month of dosing.
The pharmacokinetic parameters of sugammadex predicted by age group and renal function based on the compartmental model (using 3 compartments) are presented as follows: See Table 6.


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Gender: No gender differences were observed.
Race: In a study in healthy Japanese and Caucasian subjects no clinically relevant differences in pharmacokinetic parameters were observed. Limited data does not indicate differences in pharmacokinetic parameters in Black or African Americans.
Body weight: Population pharmacokinetic analysis of adult and elderly patients showed no clinically relevant relationship of clearance and volume of distribution with body weight.

Reversal of neuromuscular blockade induced by rocuronium or vecuronium.
For the paediatric patients: Sugammadex is only recommended for reversal of conventional neuromuscular blockade induced by rocuronium in children and adolescents (2 to 17 years of age).

Method of administration: SUGAMMADEX should only be administered intravenously as a single bolus injection. The bolus dose should be administered rapidly, within 10 seconds, by bolus injection into a vein or into an intravenous line. SUGAMMADEX was administered as a single bolus injection in clinical trials only.
If the drug is administered through an infusion line that has been used with other drugs, it is important to flush the infusion line [e.g., with sodium chloride 9 mg/mL (0.9% solution)] between administration of sugammadex and other drugs known to be incompatible with sugammadex or drugs whose compatibility with sugammadex is unknown.
Sugammadex may be injected into an infusion line already in use for intravenous infusion of the following solutions: Sodium chloride 9 mg/mL (0.9% solution), glucose 50 mg/mL (5%), sodium chloride 4.5 mg/mL (0.45%) and glucose 25 mg/mL (2.5%), lactated Ringers solution, Ringers solution, glucose 50 mg/mL (5%) in sodium chloride 9 mg/mL (0.9%).
When used for children, the drug can be diluted with sodium chloride solution 9 mg/mL (0.9% solution) to create a concentration of 10 mg/mL.
Unused medicine or waste should be disposed of according to local regulations.
Posology: Sugammadex should be administered only by or under the supervision of a qualified anaesthetist.
Appropriate neuromuscular monitoring techniques should be used to monitor recovery of neuromuscular blockade. As is usual practice following anaesthesia using neuromuscular blockade, patients should be observed in the immediate postoperative period for signs of neuromuscular blockade, including recurrence of blockade (see Precautions). Patients who have received certain parenteral drugs within 6 hours prior to administration should be monitored for signs of blockade Use of sugammadex may cause substitution interactions (see Precautions and Interactions). The recommended dose of sugammadex depends on the degree of reversal of neuromuscular blockade.
This recommended dose is independent of the method of anaesthetic.
Sugammadex can be used to reverse varying degrees of neuromuscular blockade induced by rocuronium or vecuronium.
Adults: Routine reversal: A dose of 4 mg/kg sugammadex is recommended if recovery has reached at least 1-2 post-tetanic counts (PTC) following rocuronium or vecuronium induced blockade. Median time to recovery of the T₄/T₁ ratio to 0.9 is around 3 minutes (see Pharmacology: Pharmacokinetics under Actions).
A dose of 2 mg/kg sugammadex is recommended, if spontaneous recovery has occurred up to at least the reappearance of T₂ following rocuronium or vecuronium induced blockade. Median time to recovery of the T₄/T₁ ratio to 0.9 is around 2 minutes (see Pharmacology: Pharmacokinetics under Actions).
Using the recommended doses for routine reversal will result in a slightly faster median time to recovery of the T₄/T₁ ratio to 0.9 of rocuronium when compared to vecuronium induced neuromuscular blockade (see Pharmacology: Pharmacokinetics under Actions).
Immediate reversal of rocuronium-induced blockade: If there is a clinical need for immediate reversal following administration of rocuronium a dose of 16 mg/kg sugammadex is recommended. When 16 mg/kg sugammadex is administered 3 minutes after a bolus dose of 1.2 mg/kg rocuronium bromide, a median time to recovery of the T4/T1 ratio to 0.9 of approximately 1.5 minutes can be expected (see Pharmacology: Pharmacokinetics under Actions).
There is no data to recommend the use of sugammadex for immediate reversal following vecuronium induced blockade.
Re-administration of sugammadex: In the exceptional situation of recurrence of neuromuscular blockade post-operatively (see Precautions) after an initial dose of 2 mg/kg or 4 mg/kg sugammadex, a repeat dose of 4 mg/kg sugammadex is recommended. Following a second dose of sugammadex, the patient should be closely monitored to ascertain sustained return of neuromuscular function.
Re-administration of rocuronium or vecuronium after sugammadex: For waiting times for re-administration of rocuronium or vecuronium after reversal with sugammadex, see Precautions.
Additional information on special population: Renal impairment: The use of sugammadex in patients with severe renal impairment (including patients requiring dialysis (CrCl <30 mL/min)) is not recommended (see Precautions).
Studies in patients with severe renal impairment do not provide sufficient safety information to support the use of sugammadex in these patients (see Pharmacology: Pharmacokinetics under Actions).
For mild and moderate renal impairment (creatinine clearance ≥30 and <80 mL/min): The dose recommendations are the same as for adults without renal impairment.
Elderly patients: After administration of sugammadex at reappearance of T₂ following a rocuronium induced blockade, the median time to recovery of the T₄/T₁ ratio to 0.9 in adults (18-64 years) was 2.2 minutes, in elderly adults (65-74 years) it was 2.6 minutes and in very elderly adults (75 years or more) it was 3.6 minutes. Even though the recovery times in elderly tend to be slower, the same dose recommendation as for adults should be followed (see Precautions).
Obese patients: In obese patients, the recommended dose of sugammadex should be based on the patient's actual body weight. The same recommended dose as for non-obese adults should be used.
Hepatic impairment: For mild to moderate hepatic impairment: As sugammadex is mainly excreted renally no dose adjustments are required.
Studies in patients with hepatic impairment have not been conducted. Caution should be exercised when considering the use of sugammadex in patients with severe hepatic impairment or when hepatic impairment is accompanied by coagulopathy (see Precautions).
Paediatric: Data from the paediatric population are limited (only 1 study on reversal of rocuronium blockade upon reappearance of T2).
Children and adolescents: Sugammadex 2 mg/kg should be used for routine reversal of rocuronium induced block when T2 recurs in children and adolescents (2-17 years). Other routine reversals have not been studied and therefore should not be used until further data are available.
There are no immediate reversal studies in children and adolescents and therefore the drug should not be used until further data are available.
The drug may be diluted to 10 mg/mL to increase the accuracy of dosing in pediatric patients (see previously mentioned).
Term newborn infants and infants: There is only limited experience with the use of sugammadex in infants (30 days to 2 years), and there are no studies in full-term neonates (less than 30 days). Therefore, sugammadex should not be used in term newborn infants and infants until further data are available.

In clinical studies, 1 case of an accidental overdose with 40 mg/kg was reported without any significant adverse reactions. In a human tolerance study sugammadex was administered in doses up to 96 mg/kg. No dose related adverse events nor serious adverse events were reported.
Sugammadex can be removed using haemodialysis with a high flux filter, but not with a low flux filter. Based upon clinical studies, sugammadex concentrations in plasma are reduced by up to 70% after a 3 to 6-hour dialysis session.

Patients with hypersensitivity to the active substance or to any ingredient of the drug.

Monitoring respiratory function during recovery: Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored following reversal of neuromuscular blockade. Even if recovery from neuromuscular blockade is complete, other medicinal products used in the peri- and post-operative period could depress respiratory function and therefore ventilatory support might still be required.
Should neuromuscular blockade reoccur following extubation, adequate ventilation should be provided.
Effect on haemostasis: In vitro experiments, a prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) has been observed with sugammadex in combination with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran.
In a study in volunteers, sugammadex doses of 4 mg/kg and 16 mg/kg resulted in a maximum mean prolongation of aPTT of 17% with 4 mg/kg and 22% with 16 mg/kg and a maximum mean prolongation of PT (international normalized ratio, INR) of 11% with 4 mg/kg and 22% with 16 mg/kg. These limited mean prolongations of aPTT and PT (INR) were of short duration (<=30 minutes). Based on clinical data (n=1738), there was no clinically significant effect of sugammadex alone or in combination with anticoagulants on the incidence of perioperative or postoperative bleeding complications.
Considering the transient nature of the limited prolongation of aPPT and PT caused by sugammadex alone or in combination with these anticoagulants, it is unlikely that sugammadex would cause an increased risk of bleeding. Since there is no information on the use of sugammadex in patients with known coagulation disorders, careful monitoring of coagulation parameters is recommended according to routine clinical rule.
Recurrence of neuromuscular blockade: Recurrence of neuromuscular blockade has been reported in clinical trials mainly at suboptimal doses (dose-finding studies). To prevent recurrence of neuromuscular block, the usual recommended reversal doses should be administered promptly (see Precautions).
Waiting times for re-administration with neuromuscular blocking agents after reversal with sugammadex: Re-administration of rocuronium or vecuronium after routine reversal (up to 4 mg/kg sugammadex): See Table 7.


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Based on PK modelling 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 routine reversal with sugammadex 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.
Re-administration of rocuronium or vecuronium after immediate reversal (16 mg/kg sugammadex): For the very rare cases where this might be required, a waiting time of 24 hours is suggested.
If neuromuscular blockade is required before the recommended waiting time has passed, a nonsteroidal neuromuscular blocking agent should be used. The onset of a depolarizing neuromuscular blocking agent might be slower than expected, because a substantial fraction of postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
Renal impairment: Sugammadex is not recommended for use in patients with severe renal impairment, including those requiring dialysis (see Pharmacology: Pharmacodynamics under Actions).
Interactions due to the lasting effect of rocuronium or vecuronium: When medicinal products which potentiate neuromuscular blockade are used in the post-operative period special attention should be paid to the possibility of recurrence of neuromuscular blockade. Refer to the monograph of rocuronium or vecuronium for a list of the specific medicinal products which potentiate neuromuscular blockade. In case recurrence of neuromuscular blockade is observed, the patient may require mechanical ventilation and re-administration of sugammadex (see Dosage & Administration).
Interactions: Interactions due to occupancy: Due to the administration of sugammadex, certain medicinal products could become less effective due to a lowering of the (free) plasma concentrations (see Interactions potentially affecting the efficacy of other medicinal products: Hormonal contraceptives under Interactions).
If such a situation is observed, the clinician is advised to consider the re-administration of the medicinal product, the administration of a therapeutically equivalent medicinal product (preferably from a different chemical class) and/or non-pharmacological interventions as appropriate.
Displacement interactions: Due to the administration of certain medicinal products after sugammadex, theoretically rocuronium or vecuronium could be displaced from sugammadex. As a result recurrence of neuromuscular blockade might be observed. In this situation the patient must be ventilated. Administration of the medicinal product which caused displacement should be stopped in case of an infusion. In situations when potential displacement interactions can be anticipated, patients should be carefully monitored for signs of recurrence of neuromuscular blockade (approximately up to 15 minutes) after parenteral administration of another medicinal product occurring within a period of 7.5 hours after sugammadex administration.
To date, substitution interactions have been reported with a few drugs (see Interactions potentially affecting the efficacy of sugammadex: Toremifene and Intravenous administration of fusidic acid under Interactions).
Light anaesthesia: When neuromuscular blockade was reversed intentionally in the middle of anaesthesia in clinical trials, signs of light anaesthesia were noted occasionally (movement, coughing, grimacing and suckling of the tracheal tube).
If neuromuscular blockade is reversed, while anaesthesia is continued, additional doses of anaesthetic and/or opioid should be given as clinically indicated.
Marked bradycardia: In rare instances, marked bradycardia has been observed within minutes after the administration of sugammadex for reversal of neuromuscular blockade. Bradycardia may occasionally lead to cardiac arrest. (See Adverse Reactions). Patients should be closely monitored for haemodynamic changes during and after reversal of neuromuscular blockade. Treatment with anti-cholinergic agents such as atropine should be administered if clinically significant bradycardia is observed.
Hepatic impairment: Sugammadex is not metabolised nor excreted by the liver; therefore dedicated studies in patients with hepatic impairment have not been conducted. Patients with severe hepatic impairment should be treated with great caution. In case hepatic impairment is accompanied by coagulopathy see the information on the Effect on haemostasis as previously mentioned.
Use in Intensive Care Unit (ICU): Sugammadex has not been investigated in patients receiving rocuronium or vecuronium in the ICU setting.
Use for reversal of neuromuscular blocking agents other than rocuronium or vecuronium: Sugammadex should not be used to reverse block induced by nonsteroidal neuromuscular blocking agents such as succinylcholine or benzylisoquinolinium compounds.
Sugammadex should not be used for reversal of neuromuscular blockade induced by steroidal neuromuscular blocking agents other than rocuronium or vecuronium, since there are no efficacy and safety data for these situations. Limited data are available for reversal of pancuronium induced blockade, but it is advised not to use sugammadex in this situation.
Delayed recovery: Conditions associated with prolonged circulation time such as cardiovascular disease, old age (see Dosage & Administration for the time to recovery in elderly), or oedematous state may be associated with longer recovery times.
Drug hypersensitivity reactions: Clinicians should be prepared for the possibility of drug hypersensitivity reactions and take the necessary precautions (see Adverse Reactions).
Patients on controlled sodium diets: Each mL of solution contains 9.4 mg sodium. Each dose containing 23 mg sodium is said to be "sodium free".
If more than 2.5 mL of solution is required, this should be considered in patients on a controlled salt diet.
Effects on Ability to Drive and Use Machines: There is no evidence of the effect of the drug on the ability to drive and use machines.

Pregnancy: For sugammadex no clinical data on exposed pregnancies are available.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development.
Caution should be exercised when administering sugammadex to pregnant women.
Breast-feeding: It is unknown whether sugammadex is excreted in human breast milk. Animal studies have shown excretion of sugammadex in breast milk. Oral absorption of cyclodextrins in general is low and no effect on the suckling child is anticipated following a single dose to the breast-feeding woman.
Sugammadex can be used during breast-feeding.

Sugammadex is administered concomitantly with neuromuscular blocking agents and anaesthetics in surgical patients. The causality of adverse events is therefore difficult to assess.
The most commonly reported adverse reactions in surgical patients were cough, airway complication of anaesthesia, anaesthetic complications, procedural hypotension and procedural complication (Common (≥1/100 to <1/10)).
The safety of sugammadex has been evaluated in 3,519 unique subjects across a pooled phase I-III safety database. The following adverse reactions were reported in placebo controlled trials where subjects received anaesthesia and/or neuromuscular blocking agents (1,078 subject exposures to sugammadex versus 544 to placebo). [Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000)].
The following adverse reactions have been reported in patients that are considered to be related to the use of sugammadex: See Table 8.


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Drug hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers (for information on volunteers, see Recurrence of neuromuscular blockade: Information on healthy volunteers as follows). In clinical trials of surgical patients these reactions were reported uncommonly and for post-marketing reports the frequency is unknown.
These reactions 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.
Symptoms associated with these reactions can include: Flushing, urticaria, erythematous rash, (severe) hypotension, tachycardia, swelling of tongue, swelling of pharynx, bronchospasm and pulmonary obstructive events. Severe hypersensitivity reactions can be fatal.
Airway complication of anaesthesia: Airway complications of anaesthesia included bucking against the endotracheal tube, coughing, mild bucking, arousal reaction during surgery, coughing during the anaesthetic procedure or during surgery, or anaesthetic procedure-related spontaneous breath of patient.
Anaesthetic complication: Anaesthetic complications, indicative of the restoration of neuromuscular function, include movement of a limb or the body or coughing during the anaesthetic procedure or during surgery, grimacing, or suckling on the endotracheal tube. (See Light anaesthesia under Precautions.)
Procedural complication: Procedural complications included coughing, tachycardia, bradycardia, movement, and increase in heart rate.
Marked bradycardia: In post-marketing, isolated cases of marked bradycardia and bradycardia with cardiac arrest have been observed within minutes after administration of sugammadex (see Precautions).
Recurrence of neuromuscular blockade: In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labelled for the depth of neuromuscular blockade (N=2022), an incidence of 0.20% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence (see Precautions).
Information on healthy volunteers: A randomised, double-blind study examined the incidence of drug hypersensitivity reactions in healthy volunteers given up to 3 doses of placebo (N=76), sugammadex 4 mg/kg (N=151) or sugammadex 16 mg/kg (N=148). Reports of suspected hypersensitivity were adjudicated by a blinded committee. The incidence of adjudicated hypersensitivity was 1.3%, 6.6% and 9.5% in the placebo, sugammadex 4 mg/kg and sugammadex 16 mg/kg groups, respectively. There were no reports of anaphylaxis after placebo or sugammadex 4 mg/kg. There was a single case of adjudicated anaphylaxis after the first dose of sugammadex 16 mg/kg (incidence 0.7%). There was no evidence of increased frequency or severity of hypersensitivity with repeat dosing of sugammadex.
In a previous study of similar design, there were three adjudicated cases of anaphylaxis, all after sugammadex 16 mg/kg (incidence 2.0%).
In the Pooled Phase 1 database, AEs considered common (≥1/100 to <1/10) or very common (≥1/10) and more frequent among subjects treated with sugammadex than in the placebo group, include dysgeusia (10.1%), headache (6.7%), nausea (5.6%), urticaria (1.7%), pruritus (1.7%), dizziness (1.6%), vomiting (1.2%) and abdominal pain (1.0%).
Additional information on special populations: Pulmonary patients: In post-marketing data and in one dedicated clinical trial in patients with a history of pulmonary complications, bronchospasm was reported as a possibly related adverse event. As with all patients with a history of pulmonary complications the physician should be aware of the possible occurrence of bronchospasm.
Paediatric population: In studies of paediatric patients 2 to 17 years of age, the safety profile of sugammadex (up to 4 mg/kg) was generally similar to the profile observed in adults.
Morbidly obese patients: In one dedicated clinical trial in morbidly obese patients, the safety profile was generally similar to the profile in adult patients in pooled Phase 1 to 3 studies.
Patients with severe systemic disease: In a trial in patients who were assessed as American Society of Anesthesiologists (ASA) Class 3 or 4 (patients with severe systemic disease or patients with severe systemic disease that is a constant threat to life), the adverse reaction profile in these ASA Class 3 and 4 patients was generally similar to that of adult patients in pooled Phase 1 to 3 studies.
Any adverse drug reactions should be immediately reported to the physician or pharmacist.

Drug interactions: The information in this section is based on binding affinity between sugammadex and other medicinal products, non-clinical experiments, clinical studies and simulations using a model taking into account the pharmacodynamic effect of neuromuscular blocking agents and the pharmacokinetic interaction between neuromuscular blocking agents and sugammadex. Based on these data, no clinically significant pharmacodynamic interaction with other medicinal products is expected, with exception of the following: For toremifene and fusidic acid displacement interactions could not be excluded (no clinically relevant capturing interactions are expected).
For hormonal contraceptives a clinically relevant capturing interaction could not be excluded (no displacement interactions are expected).
Interactions potentially affecting the efficacy of sugammadex (see Precautions): 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 could occur. Clinicians should be aware that the recovery of the T₄/T₁ ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of the operation.
Intravenous administration of fusidic acid: The use of fusidic acid in the pre-operative phase may give some delay in the recovery of the T₄/T₁ ratio to 0.9. No recurrence of neuromuscular blockade is expected in the post-operative phase, since the infusion rate of fusidic acid is over a period of several hours and the blood levels are cumulative over 2-3 days.
Interactions potentially affecting the efficacy of other medicinal products (see Precautions): Hormonal contraceptives: The interaction between 4 mg/kg sugammadex and a progestogen was predicted to lead to a decrease in progestogen exposure (34% of AUC) similar to the decrease seen when a daily dose of an oral contraceptive is taken 12 hours too late, which might lead to a reduction in effectiveness. For oestrogens, the effect is expected to be lower. Therefore the administration of a bolus dose of sugammadex is considered to be equivalent to one missed daily dose of oral contraceptive steroids (either combined or progestogen only). If sugammadex is administered at the same day as an oral contraceptive is taken reference is made to missed dose advice in the monograph of the oral contraceptive. In the case of non-oral hormonal contraceptives, the patient must use an additional non hormonal contraceptive method for the next 7 days and refer to the advice in the monograph of the product.
Interference with laboratory tests: In general sugammadex does not interfere with laboratory tests, with the possible exception of the serum progesterone assay and some coagulation parameters [activated partial thromboplastin time, prothrombin time (international normalized ratio)]. Changes in plasma samples with sugammadex concentrations in the same range as those achieved with Cmax after a dose of 16 mg/kg were observed. The clinical relevance of these findings is unknown as they have not been studied in patients.
Paediatric population: No formal interaction studies have been performed. The previously mentioned interactions for adults and Precautions should also be taken into account for the paediatric population.
Drug Incompatibilities: This medicinal product must not be mixed with other medicinal products.
Physical incompatibility has been reported with verapamil, ondansetron and ranitidine.

Store below 30°C. Do not freeze. Store in original packaging to protect from light. For storage conditions for the reconstituted solution, see Shelf-life as follows.
Shelf-life: 36 months from date of manufacture.
After first opening and diluting, store at 2 to 8°C and use within 24 hours.

Antidotes & Detoxifying Agents

V03AB35 - sugammadex ; Belongs to the class of antidotes. Used to reverse neuromuscular blockade caused by rocuronium or vecuronium.