Reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults.
For the paediatric population: sugammadex is only recommended for routine reversal of
rocuronium induced blockade in children and adolescents aged 2 to 17 years.

Posology
Sugammadex should only be administered by, or under the supervision of an anaesthetist.

The use of an appropriate neuromuscular monitoring technique is recommended to monitor the
recovery of neuromuscular blockade (see section 4.4).
The recommended dose of sugammadex depends on the level of neuromuscular blockade to be
reversed.
The recommended dose does not depend on the anaesthetic regimen.
Sugammadex can be used to reverse different levels of rocuronium or vecuronium induced
neuromuscular blockade:
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 section 5.1).
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 section 5.1).
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 section 5.1).
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 section 5.1).
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
section 4.4) 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 section 4.4.
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 section 4.4).
Studies in patients with severe renal impairment do not provide sufficient safety information to
support the use of sugammadex in these patients (see also section 5.1).
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 section 4.4).
Obese patients:
In obese patients, including morbidly obese patients (body mass index ≥ 40 kg/m2), the dose of
sugammadex should be based on actual body weight. The same dose recommendations as for
adults should be followed.
Hepatic impairment:
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 section 4.4).
For mild to moderate hepatic impairment: as sugammadex is mainly excreted renally no dose
adjustments are required.

Paediatric population
Children and adolescents (2-17 years):
Sudex 100 mg/mL may be diluted to 10 mg/mL to increase the accuracy of dosing in the
paediatric population (see section 6.6).
Routine reversal:
A dose of 4 mg/kg sugammadex is recommended for reversal of rocuronium induced blockade if
recovery has reached at least 1-2 PTC.
A dose of 2 mg/kg is recommended for reversal of rocuronium induced blockade at reappearance
of T2 (see section 5.1).
Immediate reversal:
Immediate reversal in children and adolescents has not been investigated.
Term newborn infants and infants:
There is only limited experience with the use of sugammadex in infants (30 days to 2 years), and
term newborn infants (less than 30 days) have not been studied. The use of sugammadex in term
newborn infants and infants is therefore not recommended until further data become available.
Method of administration
Sugammadex should be administered intravenously as a single bolus injection. The bolus
injection should be given rapidly, within 10 seconds, into an existing intravenous line (see
section 6.6). Sugammadex has only been administered as a single bolus injection in clinical
trials

As is normal post-anaesthetic practice following neuromuscular blockade, it is recommended to
monitor the patient in the immediate post-operative period for untoward events including
recurrence of neuromuscular blockade.
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.
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, an incidence of
0.20% was observed for recurrence of neuromuscular blockade as based on neuromuscular
monitoring or clinical evidence. The use of lower than recommended doses may lead to an
increased risk of recurrence of neuromuscular blockade after initial reversal and is not
recommended (see section 4.2 and section 4.8).
Effect on haemostasis:
In a study in volunteers doses of 4 mg/kg and 16 mg/kg of sugammadex resulted in maximum
mean prolongations of the activated partial thromboplastin time (aPTT) by 17 and 22%
respectively and prothrombin time international normalized ratio [PT(INR)] by 11 and 22%
respectively. These limited mean aPTT and PT(INR) prolongations were of short duration (≤ 30
minutes). Based on the clinical data-base (N=3,519) and on a specific study in 1184 patients
undergoing hip fracture/major joint replacement surgery there was no clinically relevant effect of
sugammadex 4 mg/kg alone or in combination with anticoagulants on the incidence of peri- or
post-operative bleeding complications.
In in vitro experiments a pharmacodynamic interaction (aPTT and PT prolongation) was noted
with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids,
rivaroxaban and dabigatran. In patients receiving routine post-operative prophylactic
anticoagulation this pharmacodynamic interaction is not clinically relevant. Caution should be
exercised when considering the use of sugammadex in patients receiving therapeutic
anticoagulation for a pre-existing or co-morbid condition.
An increased risk of bleeding cannot be excluded in patients:
• with hereditary vitamin K dependent clotting factor deficiencies;
• with pre-existing coagulopathies;

on coumarin derivates and at an INR above 3.5;
• using anticoagulants who receive a dose of 16 mg/kg sugammadex.
If there is a medical need to give sugammadex to these patients the anaesthesiologist needs to
decide if the benefits outweigh the possible risk of bleeding complications taking into
consideration the patients history of bleeding episodes and type of surgery scheduled. If
sugammadex is administered to these patients monitoring of haemostasis and coagulation
parameters is recommended.
Waiting times for re-administration with neuromuscular blocking agents after reversal with
sugammadex:
Table 1: Re-administration of rocuronium or vecuronium after routine reversal (up to 4
mg/kg sugammadex):
Minimum waiting time NMBA and dose to be administered
5 minutes 1.2 mg/kg rocuronium
4 hours 0.6 mg/kg rocuronium or
0.1 mg/kg vecuronium
The onset of neuromuscular blockade may be prolonged up to approximately 4 minutes, and the
duration of neuromuscular blockade may be shortened up to approximately 15 minutes after readministration
of rocuronium 1.2 mg/kg within 30 minutes after sugammadex administration.
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 section 5.1).
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 section 4.8). Patients should be closely monitored for hemodynamic 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.
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 section 4.2 for the time to recovery in elderly), or oedematous state (e.g., severe hepatic
impairment) may be associated with longer recovery times.
Drug hypersensitivity reactions:
Clinicians should be prepared for the possibility of drug hypersensitivity reactions (including
anaphylactic reactions) and take the necessary precautions (see section 4.8).
Sodium:
This medicinal product contains up to 9.7 mg sodium per mL, equivalent to 0.5 % of the WHO
recommended maximum daily intake of 2 g sodium for an adult.

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 (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.
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. For re-administration of sugammadex see section 4.2.
Interactions potentially affecting the efficacy of other medicinal products (capturing
interactions):
Due to the administration of sugammadex, certain medicinal products could become less
effective due to a lowering of the (free) plasma concentrations. 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.
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 package leaflet 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 package leaflet of the product.
Interactions due to the lasting effect of rocuronium or vecuronium:
When medicinal products which potentiate neuromuscular blockade are used in the postoperative
period special attention should be paid to the possibility of recurrence of
neuromuscular blockade. Please refer to the package leaflet 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 section 4.2).
Interference with laboratory tests:
In general sugammadex does not interfere with laboratory tests, with the possible exception of
the serum progesterone assay. Interference with this test is observed at sugammadex plasma
concentrations of 100 microgram/mL (peak plasma level following 8 mg/kg bolus injection).
In a study in volunteers doses of 4 mg/kg and 16 mg/kg of sugammadex resulted in maximum
mean prolongations of aPTT by 17 and 22% respectively and of PT(INR) by 11 and 22%
respectively. These limited mean aPTT and PT(INR) prolongations were of short duration (≤ 30
minutes).
In in vitro experiments a pharmacodynamic interaction (aPTT and PT prolongation) was noted
with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids,
rivaroxaban and dabigatran (see section 4.4).
Paediatric population
No formal interaction studies have been performed. The above mentioned interactions for adults
and the warnings in section 4.4 should also be taken into account for the paediatric population.

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 breastfeeding
woman.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from
sugammadex therapy, taking into account the benefit of breast feeding for the child and the
benefit of therapy for the woman.
Fertility
The effects with sugammadex on human fertility have not been investigated. Animal studies to
evaluate fertility do not reveal harmful effects.

Sudex has no known influence on the ability to drive and use machines

Summary of the safety profile
Sudex 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)).
Table 2: Tabulated list of adverse reactions
The safety of sugammadex has been evaluated in 3,519 unique subjects across a pooled phase IIII
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)]

System organ class Frequencies Adverse reactions
(Preferred terms)
Immune system disorders Uncommon Drug hypersensitivity
reactions (see section 4.4)
Respiratory, thoracic and
mediastinal disorders
Common Cough
Injury, poisoning and
procedural complications
Common Airway complication of
anaesthesia
Anaesthetic complication
(see section 4.4)
Procedural hypotension
Procedural complication
Description of selected adverse reactions
Drug hypersensitivity reactions:
Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers
(for information on volunteers, see Information on healthy volunteers below). 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 section 4.4 light anaesthesia.
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 section 4.4).
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=2,022), an
incidence of 0.20% was observed for recurrence of neuromuscular blockade as based on
neuromuscular monitoring or clinical evidence (see section 4.4).
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,

Module-1
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
A limited database suggests that the safety profile of sugammadex (up to 4 mg/kg) in paediatric
patients was similar to that in adults.
Morbidly obese patients
In one dedicated clinical trial in morbidly obese patients, the adverse reaction profile was
generally similar to the profile in adult patients in pooled Phase 1 to 3 studies (see Table 2).
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 (see Table 2). See section
5.1.

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.

Pharmacotherapeutic group: all other therapeutic products, antidotes, ATC code: V03AB35
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:
Table 3: 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
Neuromuscular blocking
agent
Treatment regimen
Sugammadex (4 mg/kg) Neostigmine (70 mcg/kg)
Rocuronium
N 37 37
Median (minutes) 2.7 49.0
Range 1.2-16.1 13.3-145.7
Vecuronium
N 47 36
Median (minutes) 3.3 49.9
Range 1.4-68.4 46.0-312.7
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:
Table 4: 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
Neuromuscular blocking
agent
Treatment regimen
Sugammadex (2 mg/kg) Neostigmine (50 mcg/kg)
Rocuronium
N 48 48
Median (minutes) 1.4 17.6
Range 0.9-5.4 3.7-106.9
Vecuronium
N 48 45
Median (minutes) 2.1 18.9
Range 1.2-64.2 2.9-76.2
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:
Table 5: 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
Neuromuscular blocking
agent
Treatment regimen
Rocuronium and
sugammadex (2 mg/kg)
Cis-atracurium and
neostigmine (50 mcg/kg)
N 34 39

Median (minutes) 1.9 7.2
Range 0.7-6.4 4.2-28.2
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 rocuroniuminduced
neuromuscular blockade (1.2 mg/kg).
Table 6: Time (minutes) from administration of rocuronium and sugammadex or
succinylcholine to recovery of the T1 10%
Neuromuscular blocking
agent
Treatment regimen
Rocuronium and
sugammadex (16 mg/kg)
Succinylcholine (1 mg/kg)
N 55 55
Median (minutes) 4.2 7.1
Range 3.5-7.7 3.7-10.5
In a pooled analysis the following recovery times for 16 mg/kg sugammadex after 1.2 mg/kg
rocuronium bromide were reported:
Table 7: 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
T4/T1 to 0.9 T4/T1 to 0.8 T4/T1 to 0.7
N 65 65 65
Median
(minutes)
1.5 1.3 1.1
Range 0.5-14.3 0.5-6.2 0.5-3.3
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.
Morbidly obese patients:
A trial of 188 patients who were diagnosed as morbidly obese 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, as appropriate for level of block, dosed according to
either actual body weight or ideal body weight 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 actual body weight (1.8 minutes) was statistically
significantly faster (p < 0.0001) compared to patients dosed by ideal body weight (3.3 minutes).
Patients with severe systemic disease:
A trial of 331 patients who were assessed as ASA Class 3 or 4 investigated the incidence of
treatment-emergent arrhythmias (sinus bradycardia, sinus tachycardia, or other cardiac
arrhythmias) after administration of sugammadex.
In patients receiving sugammadex (2 mg/kg, 4 mg/kg, or 16 mg/kg), the incidence of treatmentemergent
arrhythmias was generally similar to neostigmine (50 μg/kg up to 5 mg maximum
dose) + glycopyrrolate (10 μg/kg up to 1 mg maximum dose). The adverse reaction profile in
ASA Class 3 and 4 patients was generally similar to that of adult patients in pooled Phase 1 to 3
studies; therefore, no dosage adjustment is necessary. See section 4.8.
5.2 Pharmacokinetic properties
The sugammadex pharmacokinetic parameters were calculated from the total sum of noncomplex-
bound and complex-bound concentrations of sugammadex. Pharmacokinetic
parameters as clearance and volume of distribution are assumed to be the same for non-complexbound
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 anaesthetized patients with normal renal function the elimination half-life (t1/2) of
sugammadex is about 2 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 a pharmacokinetic study comparing patients with severe renal impairment to patients with
normal renal function, sugammadex levels in plasma were similar during the first hour after
dosing, and thereafter the levels decreased faster in the control group. Total exposure to
sugammadex was prolonged, leading to 17-fold higher exposure in patients with severe renal
impairment. Low concentrations of sugammadex are detectable for at least 48 hours post-dose in
patients with severe renal insufficiency.
In a second study comparing subjects with moderate or severe renal impairment to subjects with
normal renal function, sugammadex clearance progressively decreased and t1/2 was progressively
prolonged with declining renal function. Exposure was 2-fold and 5-fold higher in subjects with
moderate and severe renal impairment, respectively. Sugammadex concentrations were no longer
detectable beyond 7 days post-dose in subjects with severe renal insufficiency.

Table 8: A summary of sugammadex pharmacokinetic parameters stratified by age and
renal function is presented below:
Selected patient characteristics Mean Predicted PK parameters (CV%)
Demographics Renal function
Creatinine clearance
(mL/min)
Clearance
(mL/min)
Volume of
distribution at
steady state (L)
Elimination halflife
(hr)
Adult Normal
100 88 (22) 12 2 (21)
40 yrs Impaired Mild 50 51 (22) 13 4 (22)
75 kg
Moderate 30 31 (23) 14 6 (23)
Severe 10 9 (22) 14 19 (24)
Elderly Normal
80 75 (23) 12 2 (21)
75 yrs Impaired Mild 50 51 (24) 13 3 (22)
75 kg
Moderate 30 31 (23) 14 6 (23)
Severe 10 9 (22) 14 19 (23)
Adolescent Normal
95 77 (23) 9 2 (22)
15 yrs Impaired Mild 48 44 (23) 10 3 (22)
56 kg
Moderate 29 27 (22) 10 5 (23)
Severe 10 8 (21) 11 17 (23)
Child Normal
51 37 (22) 4 2 (20)
7 yrs Impaired Mild 26 19 (22) 4 3 (22)
23 kg
Moderate 15 11 (22) 4 5 (22)
Severe 5 3 (22) 5 20 (25)
CV=coefficient of variation
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.
Obesity:
In one clinical study in morbidly obese patients, sugammadex 2 mg/kg and 4 mg/kg was dosed
according to actual body weight (n=76) or ideal body weight (n=74). Sugammadex exposure
increased in a dose-dependent, linear manner following administration according to actual body
weight or ideal body weight. No clinically relevant differences in pharmacokinetic parameters
were observed between morbidly obese patients and the general population.

5.2 Pharmacokinetic properties
The sugammadex pharmacokinetic parameters were calculated from the total sum of noncomplex-
bound and complex-bound concentrations of sugammadex. Pharmacokinetic
parameters as clearance and volume of distribution are assumed to be the same for non-complexbound
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 anaesthetized patients with normal renal function the elimination half-life (t1/2) of
sugammadex is about 2 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 a pharmacokinetic study comparing patients with severe renal impairment to patients with
normal renal function, sugammadex levels in plasma were similar during the first hour after
dosing, and thereafter the levels decreased faster in the control group. Total exposure to
sugammadex was prolonged, leading to 17-fold higher exposure in patients with severe renal
impairment. Low concentrations of sugammadex are detectable for at least 48 hours post-dose in
patients with severe renal insufficiency.
In a second study comparing subjects with moderate or severe renal impairment to subjects with
normal renal function, sugammadex clearance progressively decreased and t1/2 was progressively
prolonged with declining renal function. Exposure was 2-fold and 5-fold higher in subjects with
moderate and severe renal impairment, respectively. Sugammadex concentrations were no longer
detectable beyond 7 days post-dose in subjects with severe renal insufficiency.

Table 8: A summary of sugammadex pharmacokinetic parameters stratified by age and
renal function is presented below:
Selected patient characteristics Mean Predicted PK parameters (CV%)
Demographics Renal function
Creatinine clearance
(mL/min)
Clearance
(mL/min)
Volume of
distribution at
steady state (L)
Elimination halflife
(hr)
Adult Normal
100 88 (22) 12 2 (21)
40 yrs Impaired Mild 50 51 (22) 13 4 (22)
75 kg
Moderate 30 31 (23) 14 6 (23)
Severe 10 9 (22) 14 19 (24)
Elderly Normal
80 75 (23) 12 2 (21)
75 yrs Impaired Mild 50 51 (24) 13 3 (22)
75 kg
Moderate 30 31 (23) 14 6 (23)
Severe 10 9 (22) 14 19 (23)
Adolescent Normal
95 77 (23) 9 2 (22)
15 yrs Impaired Mild 48 44 (23) 10 3 (22)
56 kg
Moderate 29 27 (22) 10 5 (23)
Severe 10 8 (21) 11 17 (23)
Child Normal
51 37 (22) 4 2 (20)
7 yrs Impaired Mild 26 19 (22) 4 3 (22)
23 kg
Moderate 15 11 (22) 4 5 (22)
Severe 5 3 (22) 5 20 (25)
CV=coefficient of variation
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.
Obesity:
In one clinical study in morbidly obese patients, sugammadex 2 mg/kg and 4 mg/kg was dosed
according to actual body weight (n=76) or ideal body weight (n=74). Sugammadex exposure
increased in a dose-dependent, linear manner following administration according to actual body
weight or ideal body weight. No clinically relevant differences in pharmacokinetic parameters
were observed between morbidly obese patients and the general population.

Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity potential, and toxicity to reproduction, local
tolerance or compatibility with blood.
Sugammadex is rapidly cleared in preclinical species, although residual sugammadex was
observed in bone and teeth of juvenile rats. Preclinical studies in young adult and mature rats
demonstrate that sugammadex does not adversely affect tooth colour or bone quality, bone
structure, or bone metabolism. Sugammadex has no effects on fracture repair and remodelling of
bone.
6. Pharmaceutical

Sodium Hydroxide (to adjust pH), Hydrochloric acid (to adjust pH) and water for injection

This medicinal product must not be mixed with other medicinal products except those mentioned
in section 6.6.

Store below 30°C.
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the diluted medicinal product, see section 6.3.

Vial pack

can be injected into the intravenous line of a running infusion with the following
intravenous solutions: sodium chloride 9 mg/mL (0.9%), glucose 50 mg/mL (5%), sodium
chloride 4.5 mg/mL (0.45%) and glucose 25 mg/mL (2.5%), Ringers lactate solution, Ringers
solution, glucose 50 mg/mL (5%) in sodium chloride 9 mg/mL (0.9%).
The infusion line should be adequately flushed (e.g., with 0.9% sodium chloride) between
administration of Sudex and other drugs.
Use in the paediatric population
For paediatric patients Sudex can be diluted using sodium chloride 9 mg/mL (0.9%) to a
concentration of 10 mg/mL.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how
to throw away medicines you no longer use. These measures will help protect the environment