Sugammadex Mylan

Package leaflet: Information for the user

Sugammadex Mylan 100 mg/mL solution for injection

sugammadex
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your anaesthetist or doctor.
• If you experience any side effects, including those not listed in this leaflet, inform your anaesthetist or another doctor. See section 4.

Contents of this leaflet

1. What Sugammadex Mylan is and what it is used for
2. What you need to know before you are given Sugammadex Mylan
3. How Sugammadex Mylan is administered
4. Possible side effects
5. How to store Sugammadex Mylan
6. Contents of the pack and other information

1. What is Sugammadex Mylan and what is it used for

What is Sugammadex Mylan
Sugammadex Mylan contains the active substance sugammadex. Sugammadex Mylan is considered
to be a selective relaxant binding agent because it selectively binds to other medicines, rocuronium
bromide or vecuronium bromide, known as muscle relaxants, which relax the muscles.
What is Sugammadex Mylan used for
During certain types of surgery, muscles need to be completely relaxed. This makes the surgeon’s task
easier. For this purpose, muscle relaxant medicines are added to the general anaesthesia administered.
These medicines are called muscle relaxants, and include rocuronium bromide and vecuronium
bromide. Since these medicines also relax the muscles that control breathing, assistance with
breathing (so-called artificial ventilation) is required during and after surgery, until you are able to
breathe on your own again.
Sugammadex Mylan is used to speed up the recovery of muscle function after surgery, allowing you
to breathe on your own again as soon as possible. It works by binding to rocuronium bromide or
vecuronium bromide present in the body. It can be used in adults whenever rocuronium bromide or
vecuronium bromide is used.
It can be used in neonates, infants, young children, children, and adolescents (from birth up to 17 years
of age) when rocuronium bromide is used.

2. What you need to know before Sugammadex Mylan is administered

Do not receive Sugammadex Mylan

• if you are allergic to sugammadex or to any of the other ingredients of this medicine (listed in section 6). Inform your anaesthetist if this applies to you.

Warnings and precautions
Inform your anaesthetist before Sugammadex Mylan is administered

• if you have or have previously had kidney disease. This is important because sugammadex is eliminated from the body through the kidneys.
• if you have or have previously had liver disease.
• if you have fluid retention (oedema).
• if you have conditions known to increase the risk of bleeding (blood coagulation disorders) or if you are taking anticoagulant therapy.

Other medicines and Sugammadex Mylan
Inform your anaesthetist if you are taking, have recently taken, or might take any other
medicines. Sugammadex Mylan may affect or be affected by other medicines.
Some medicines reduce the effect of Sugammadex Mylan
It is particularly important that you inform your anaesthetist if you have recently taken:

• toremifene (used to treat breast cancer).
• fusidic acid (an antibiotic).

Sugammadex Mylan may affect hormonal contraceptives
Sugammadex Mylan may reduce the effectiveness of hormonal contraceptives – including oral
contraceptives, vaginal ring, implant, or hormonal intrauterine system (IUS) – because it reduces the
amount of absorbed progestogenic hormone. The amount of progestogen lost when Sugammadex Mylan is used is approximately equivalent to missing one dose of the oral contraceptive pill.

• If you need to take the oral contraceptive pill on the same day that Sugammadex Mylan is administered, follow the instructions in the contraceptive pill’s package leaflet regarding a missed dose.
• If you are using other hormonal contraceptives (e.g. a vaginal ring, implant, or IUS), you should use an additional non-hormonal contraceptive method (such as a condom) for the next 7 days and follow the instructions provided in the product leaflet.

Effects on blood test results
In general, Sugammadex Mylan has no effect on blood test results. However, it may interfere with test results measuring blood levels of a hormone called progesterone.
Please consult your doctor if testing of progesterone levels is required on the same day you receive Sugammadex Mylan.
Pregnancy and breastfeeding
Inform your anaesthetist if you are pregnant, suspect you may be pregnant, or if you are breastfeeding.
You may still receive Sugammadex Mylan, but you must discuss this with your doctor first.
It is not known whether sugammadex passes into breast milk. Your anaesthetist will help you decide whether to discontinue breastfeeding or to refrain from treatment with sugammadex, taking into account the benefits of breastfeeding for the infant and the benefits of Sugammadex Mylan for the mother.
Driving and using machines
Sugammadex Mylan has no known influence on the ability to drive vehicles or use machinery.
Sugammadex Mylan contains sodium
This medicine contains up to 9.2 mg of sodium (the main component of table salt) per mL. This corresponds to 0.5% of the maximum daily recommended dietary intake for an adult.

3. How Sugammadex Mylan is administered

Sugammadex Mylan will be administered to you by an anaesthetist or under the supervision of an anaesthetist.
The dose
The anaesthetist will determine the appropriate dose of Sugammadex Mylan for you, taking into consideration:

• your body weight
• the extent to which the muscle relaxant is still affecting you.

The usual dose is 2–4 mg per kg of body weight in patients of any age. A dose of
16 mg/kg may be used in adults if rapid reversal of muscle relaxation is required.
How Sugammadex Mylan is administered
Sugammadex Mylan will be administered by the anaesthetist as a single intravenous injection.
If you are given more Sugammadex Mylan than recommended
Since your condition will be closely monitored by the anaesthetist, it is unlikely that you will receive an excessive amount of Sugammadex Mylan. However, if this were to happen, it is unlikely to cause you any problems.
If you have any doubts about the use of this medicine, consult the anaesthetist or your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. If such side effects occur during anaesthesia, they will be detected and treated by the anaesthesiologist.

Common side effects (may affect up to 1 in 10 people)

• Cough
• Breathing difficulties which may include coughing or movements as if waking up or gasping for breath
• Light anaesthesia – you may begin to come out of deep sleep, and therefore may require additional anaesthetic. This may cause the patient to move or cough at the end of the operation
• Complications during the procedure such as changes in heart rate, coughing or movements
• Decrease in blood pressure due to the surgical procedure

Uncommon side effects (may affect up to 1 in 100 people)

• In patients with a history of lung problems, shortness of breath due to muscle contractions of the airways (bronchospasm) has been observed
• Allergic reactions (hypersensitivity to the medicine), such as skin rash, flushed skin, swelling of the tongue and/or throat, shortness of breath, changes in blood pressure or heart rate, which sometimes may lead to severe drops in blood pressure. Severe allergic or allergic-like reactions can be life-threatening. Allergic reactions have been reported more commonly in healthy, awake volunteers
• Return of muscle relaxation after the operation

Frequency not known

• When Sugammadex Mylan is administered, severe slowing of the heart and slowing of the heart to the point of cardiac arrest may occur.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your anaesthesiologist or another doctor. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sugammadex Mylan

Storage will be managed by healthcare professionals.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.
Store below 30 °C. Do not freeze. Keep the vial in the outer packaging to protect the medicine from light.
After first opening and dilution, store between 2 °C and 8 °C and use within 24 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sugammadex Mylan contains

• The active substance is sugammadex. 1 mL of injectable solution contains sodium sugammadex equivalent to 100 mg of sugammadex. Each 2 mL vial contains sodium sugammadex equivalent to 200 mg of sugammadex. Each 5 mL vial contains sodium sugammadex equivalent to 500 mg of sugammadex.
• The other components are water for injections, hydrochloric acid and/or sodium hydroxide.

Description of the appearance of Sugammadex Mylan and contents of the pack
Sugammadex Mylan is a clear, colourless to pale yellow injectable solution. It is available in
four different pack sizes, containing either 1 or 10 vials with 2 mL of injectable solution or 1 or
10 vials with 5 mL of injectable solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mylan Pharmaceuticals Limited
Damastown Industrial Park,
Mulhuddart, Dublin 15,
Dublin,
Ireland

Manufacturer
Viatris Santé
1 rue de Turin
69007 Lyon
France
Eurofins BioPharma Product Testing Budapest Kft
Anonymus Utca 6, Kerulet,
Budapest IV, 1045
Hungary
Mylan Germany GmbH
Benzstrasse 1
Bad Homburg
61352 Hesse
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Viatris Viatris UAB
Tél/Tel: +32 (0)2 658 61 00 Tel.: +370 5 205 1288

България Luxembourg/Luxemburg
Майлан ЕООД Viatris
Тел.: +359 2 44 55 400 Tél/Tel: +32 (0)2 658 61 00
(Belgique/Belgien)

Česká republika Magyarország
Viatris CZ s.r.o. Viatris Healthcare Kft.
Tel.: +420 222 004 400 Tel.: +36 1 465 2100

Danmark Malta
Viatris ApS V.J. Salomone Pharma Ltd
Tlf: +45 28 11 69 32 Tel: +356 21 22 01 74

Deutschland Nederland
Viatris Healthcare GmbH Mylan BV
Tel: +49 800 0700 800 Tel.: (+31 (0)20 426 3300

Eesti Norge
Viatris OÜ Viatris AS
Tel: + 372 6363 052 Tlf: +47 66 75 33 00

Ελλάδα Österreich
Viatris Hellas Ltd Viatris Austria GmbH
Τηλ: +30 2100 100 002 Tel: +43 1 86390

España Polska
Viatris Pharmaceuticals, S.L. Viatris Healthcare Sp. z o.o.
Tel: +34 900 102 712 Tel.: +48 22 546 64 00

France Portugal
Viatris Santé Mylan, Lda
Tél: +33 4 37 25 75 00 Tel: + 351 21 412 72 00

Hrvatska România
Viatris Hrvatska d.o.o. BGP Products SRL
Tel: + 385 1 23 50 599 Tel: + 40 372 579 000

Ireland Slovenija
Viatris Limited Viatris d.o.o.
Tel: +353 1 8711600 Tel: + 386 1 23 63 180

Ísland Slovenská republika
Icepharma hf. Viatris Slovakia s.r.o.
Sími: +354 540 8000 Tel: +421 2 32 199 100

Italia Suomi/Finland
Viatris Italia S.r.l. Viatris Oy
Tel: + 39 (0) 2 612 46921 Puh/Tel: +358 20 720 9555

Κύπρος Sverige
CPO Pharmaceuticals Limited Viatris AB
Τηλ: +357 22863100 Tel: +46 (0) 8 630 19 00

Latvija
Viatris SIA
Tel: +371 676 055 80

More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

For detailed information, refer to the Summary of Product Characteristics (SmPC) of
Sugammadex Mylan.
Therapeutic indications and dosage
Reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults.
For the paediatric population: sugammadex is recommended only for routine reversal of
rocuronium-induced blockade in paediatric patients from birth up to 17 years of age.
Sugammadex must be administered only by an anaesthetist or under their supervision. Adequate
neuromuscular monitoring is recommended to assess recovery from neuromuscular blockade (see SmPC,
section 4.4).
Adults
Routine reversal:
If recovery from rocuronium- or vecuronium-induced blockade has reached a post-tetanic count (PTC)
of at least 1–2, the recommended dose of sugammadex is 4 mg/kg body weight. The median time to
recovery to a T\textsubscript{4}/T\textsubscript{1} ratio of 0.9 is approximately 3 minutes (see SmPC, section 5.1).
A dose of 2 mg/kg body weight of sugammadex is recommended when spontaneous recovery has
progressed to the reappearance of T\textsubscript{4} after rocuronium- or vecuronium-induced blockade. The median
time to recovery to a T\textsubscript{4}/T\textsubscript{1} ratio of 0.9 is approximately 2 minutes (see SmPC, section 5.1).
Use of the recommended doses for routine reversal results in a slightly faster median recovery time to a
T\textsubscript{4}/T\textsubscript{1} ratio of 0.9 for rocuronium compared with neuromuscular blockade induced by vecuronium
(see SmPC, section 5.1).
Immediate reversal of rocuronium-induced blockade:
When clinically necessary to achieve immediate reversal after administration of rocuronium, a dose of
16 mg/kg body weight of sugammadex is recommended. When 16 mg/kg body weight of
sugammadex is administered 3 minutes after a 1.2 mg/kg bolus dose of rocuronium bromide, a median
time to recovery to a T\textsubscript{4}/T\textsubscript{1} ratio of 0.9 of approximately 1.5 minutes can be expected (see SmPC,
section 5.1).
There are no data to support the use of sugammadex for immediate reversal after vecuronium-induced
blockade.
Re-administration of sugammadex:
In the rare event of recurrent neuromuscular blockade in the postoperative setting (see SmPC, section
4.4), following an initial dose of 2 mg/kg or 4 mg/kg of sugammadex, administration of an additional
4 mg/kg dose of sugammadex is recommended.
After a second dose of sugammadex, the patient must be closely monitored to ensure recovery of
neuromuscular function.
Renal impairment:
The use of sugammadex in patients with severe renal impairment (including patients requiring dialysis
(CrCl < 30 mL/min)) is not recommended (see SmPC, section 4.4).
Obese patients:
In obese patients, including those with morbid obesity (body mass index ≥ 40 kg/m²), the dose of
sugammadex should be based on total body weight. The same dosing recommendations as for adults
should be followed.
Paediatric population (from birth up to 17 years of age)
Sugammadex Mylan may be diluted to 10 mg/mL to improve dosing accuracy in the paediatric
population (see SmPC, section 6.6).
Routine reversal:
A dose of 4 mg/kg sugammadex is recommended for reversal of rocuronium-induced blockade when
recovery has reached a PTC of at least 1–2.
A dose of 2 mg/kg sugammadex is recommended for reversal of rocuronium-induced blockade upon
reappearance of T\textsubscript{4} (see SmPC, section 5.1).
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.
Special warnings and precautions for use
As in standard post-anaesthesia practice, patients should be monitored in the immediate postoperative
period after neuromuscular blockade to exclude adverse events, including recurrence of neuromuscular
blockade.
Respiratory function monitoring during recovery:
After reversal of neuromuscular blockade, patients should receive respiratory support until adequate
spontaneous respiration is restored. Even when reversal of neuromuscular blockade is complete, other
medicinal products used in the peri- and postoperative period may depress respiratory function, and
respiratory support may therefore still be required.
If recurrence of neuromuscular blockade occurs after extubation, adequate ventilation must be provided.
Recurrence of neuromuscular blockade:
In clinical studies involving subjects treated with rocuronium or vecuronium, where sugammadex was
administered at doses indicated for deep neuromuscular blockade, an incidence of 0.20% of recurrence
of neuromuscular blockade was observed based on neuromuscular monitoring or clinical evidence. Use
of lower than recommended doses may increase the risk of recurrence of neuromuscular blockade after
initial reversal and is not recommended (see SmPC, 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 a maximum
prolongation of the mean activated partial thromboplastin time (aPTT) by 17% and 22%, and of the
prothrombin time international normalised ratio [PT(INR)] by 11% and 22%, respectively. These minor
prolongations of mean aPTT and PT(INR) were of short duration (≤ 30 minutes). Based on clinical
databases (N=3,519) and a specific study in 1,184 patients undergoing hip fracture surgery/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 postoperative bleeding complications.
In vitro studies have shown a pharmacodynamic interaction (prolongation of aPTT and PT) with vitamin
K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran.
This pharmacodynamic interaction is not clinically relevant in patients receiving routine postoperative
anticoagulant prophylaxis. Caution should be exercised when considering the use of sugammadex in
patients receiving anticoagulant therapy for a pre-existing or comorbid condition.
An increased risk of bleeding cannot be excluded in patients:

• with hereditary deficiencies of vitamin K-dependent coagulation factors;
• with pre-existing coagulopathies;
• treated with coumarin derivatives and with an INR greater than 3.5;
• using anticoagulants and receiving a dose of 16 mg/kg of sugammadex.

If there is a medical need to administer sugammadex to these patients, the anaesthetist must decide whether the benefits outweigh the potential risks of bleeding complications, taking into account the patient's history of bleeding episodes and the type of planned surgical procedure. If sugammadex is administered to these patients, monitoring of haemostasis and coagulation parameters is recommended.

Waiting times for re-administration of neuromuscular blocking agents after reversal with
sugammadex:
Table 1: Re-administration of rocuronium or vecuronium after routine reversal (up to
4 mg/kg sugammadex):

The onset of neuromuscular block may be prolonged by up to approximately 4 minutes, and the duration of neuromuscular block may be reduced by up to approximately 15 minutes after re-administration of 1.2 mg/kg rocuronium within 30 minutes following sugammadex administration.
Based on pharmacokinetic models in patients with mild or moderate renal impairment, the recommended waiting time before re-use of 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium after routine reversal with sugammadex is 24 hours. If a shorter waiting time is required, the dose of rocuronium for a new neuromuscular block should be 1.2 mg/kg.
Re-administration of rocuronium or vecuronio after immediate reversal (16 mg/kg sugammadex): for the very rare cases in which this may be necessary, a waiting time of 24 hours is recommended.
If it is necessary to establish a neuromuscular block before the recommended waiting time has elapsed, a non-steroidal neuromuscular blocking agent should be used. The onset of effect of a depolarizing neuromuscular blocking agent may be slower than expected, since a substantial fraction of postjunctional nicotinic receptors may still be occupied by the neuromuscular blocking agent.

Renal impairment:
The use of sugammadex is not recommended in patients with severe renal impairment, including those patients requiring dialysis (see SmPC, section 5.1).

Light anaesthesia:
In clinical studies, signs of light anaesthesia (movements, coughing, grimacing, and endotracheal tube sucking) have occasionally been observed during intentional reversal of neuromuscular block under anaesthesia.
If neuromuscular block is reversed while anaesthesia is still present, additional doses of anaesthetic and/or opioid should be administered as clinically indicated.

Marked bradycardia:
In rare cases, marked bradycardia has been observed a few minutes after administration of sugammadex for reversal of neuromuscular block. Bradycardia may occasionally lead to cardiac arrest (see SmPC, section 4.8). Patients must be closely monitored for haemodynamic changes during and after reversal of neuromuscular block. If clinically significant bradycardia occurs, treatment with anticholinergic agents such as atropine should be administered.

Hepatic impairment:
Since sugammadex is not metabolized or excreted via the liver, studies have not been conducted in patients with hepatic impairment. Patients with severe hepatic impairment should be treated with great caution. If hepatic impairment is accompanied by coagulopathy, see information regarding the effect on haemostasis.

Use in intensive care units:
Sugammadex has not been studied in patients who have received rocuronium or vecuronium in an intensive care unit.

Use for reversal of neuromuscular block induced by neuromuscular blocking agents other than rocuronium and vecuronium:
Sugammadex must not be used to reverse neuromuscular block induced by non-steroidal neuromuscular blocking agents, such as succinylcholine or benzylisoquinolinium compounds.
Sugammadex must not be used to reverse neuromuscular block induced by steroidal neuromuscular blocking agents other than rocuronium and vecuronium, as there are no data available on efficacy and safety in these circumstances. Limited data are available on reversal of pancuronium-induced block, but use of sugammadex is not recommended in this case.

Delayed recovery:
Conditions associated with prolonged circulation time, such as cardiovascular disease, advanced age (for recovery time in the elderly, see SmPC, section 4.2), or oedematous state (e.g., severe hepatic impairment), may be associated with longer recovery times.

Hypersensitivity reactions to the drug:
Physicians must be prepared for the possibility of hypersensitivity reactions to the drug (including anaphylactic reactions) and take the necessary precautions (see SmPC, section 4.8).

Sodium:
This medicinal product contains up to 9.2 mg of sodium per mL, equivalent to 0.5% of the maximum daily intake recommended by the WHO, corresponding to 2 g of sodium for an adult.

Interaction with other medicinal products and other forms of interaction
The information reported in this section is based on the binding affinity between sugammadex and other medicinal products, non-clinical studies, clinical studies, and simulations using a model that considered the pharmacodynamic effect of neuromuscular blocking agents and the pharmacokinetic interaction between neuromuscular blocking agents and sugammadex. Based on these data, clinically significant pharmacodynamic interactions with other medicinal products are not expected, except for the following:
For toremifene and fusidic acid, displacement interactions could not be excluded (no clinically relevant sequestration interactions are expected).
For hormonal contraceptives, a clinically relevant sequestration interaction could not be excluded (no displacement interactions are expected).

Interactions that may compromise the efficacy of sugammadex (displacement interactions):
The administration of certain medicinal products after sugammadex may theoretically displace rocuronium or vecuronium from sugammadex. This may result in recurrence of neuromuscular block. In such an event, the patient must be ventilated. If an infusion is ongoing, administration of the medicinal product causing displacement must be stopped. In situations where potential displacement interactions are expected, patients must be closely monitored for signs of recurrence of neuromuscular block (for a maximum period of approximately 15 minutes) if another medicinal product is administered intravenously within 7.5 hours after sugammadex administration.

Toremifene:
With regard to toremifene, which has a relatively high binding affinity for sugammadex and for which relatively high plasma concentrations may be present, some displacement of vecuronium or rocuronium from sugammadex may occur. Physicians should be aware that restoration of a T₄/T₁ ratio of 0.9 may therefore be delayed in patients who have received toremifene on the same day as surgery.

Intravenous administration of fusidic acid:
The use of fusidic acid in the preoperative phase may result in some delay in the restoration of a T₄/T₁ ratio of 0.9. In the postoperative phase, recurrence of neuromuscular block is not expected, as the infusion rate of fusidic acid lasts several hours and blood levels accumulate over 2–3 days. For re-administration of sugammadex, see SmPC, section 4.2.

Interactions that may compromise the efficacy of other medicinal products (sequestration interactions):
Administration of sugammadex may cause a reduction in the efficacy of certain medicinal products due to reduced plasma concentrations (free). If this occurs, the physician should consider the need to re-administer the medicinal product, administer a therapeutically equivalent medicinal product (preferably of a different chemical class), and/or implement non-pharmacological interventions, as appropriate.

Hormonal contraceptives:
It has been estimated that the interaction between 4 mg/kg sugammadex and a progestogen results in a reduction in progestogen exposure (34% of AUC) similar to that observed when a daily dose of oral contraceptive is taken with a 12-hour delay, an event that may reduce contraceptive efficacy. For estrogens, the effect is presumed to be less pronounced. Therefore, administration of a bolus dose of sugammadex is considered equivalent to missing one daily dose of oral steroid contraceptives (combined or progestogen-only). If sugammadex is administered on the same day as an oral contraceptive is taken, reference should be made to the instructions in the oral contraceptive’s package leaflet regarding missed doses. In the case of non-oral hormonal contraceptives, the patient should use an additional non-hormonal contraceptive method for the following 7 days and refer to the instructions in the medicinal product’s package leaflet.

Interactions due to prolonged effect of rocuronium or vecuronium:
When using medicinal products in the postoperative period that potentiate neuromuscular block, particular attention must be paid to the possible recurrence of neuromuscular block. Refer to the package leaflet of rocuronium or vecuronium for a list of specific medicinal products that potentiate neuromuscular block. If recurrence of neuromuscular block occurs, the patient may require mechanical ventilation and re-administration of sugammadex (see SmPC, section 4.2).

Fertility, pregnancy and lactation

Pregnancy
There are no clinical data on pregnancies exposed to sugammadex.
Animal studies do not indicate direct or indirect harmful effects related to pregnancy, embryonic/fetal development, parturition, or postnatal development.
Caution should be exercised when administering the medicinal product to pregnant women.

Lactation
It is not known whether sugammadex is excreted in human milk. Animal studies have shown excretion of sugammadex in milk. Oral absorption of cyclodextrins in general is low, and no effects on the breastfed infant are expected after administration of a single dose to a breastfeeding woman.
A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from treatment with sugammadex, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility
The effects of sugammadex on fertility in humans have not been studied. Animal studies to assess fertility did not reveal harmful effects.

Undesirable effects

Summary of safety profile
Sugammadex Mylan is administered concomitantly with neuromuscular blocking agents and anaesthetics in surgical patients. Therefore, causality of adverse events is difficult to assess. The most commonly reported adverse reactions in surgical patients were cough, anaesthetic respiratory complication, anaesthetic complication, procedural hypotension, and procedural complication (Common (≥ 1/100, < 1/10)).

Table 2: Table of adverse reactions
The safety of sugammadex has been evaluated in 3,519 unique subjects through a safety database from combined phase I–III studies. In placebo-controlled studies in which subjects received anaesthesia and/or neuromuscular blocking agents (1,078 subjects exposed to sugammadex versus 544 exposed to placebo), the following adverse reactions were reported:
[Very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000)]

Description of selected adverse reactions
Drug hypersensitivity reactions:
Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers (for information on volunteers, see below, Healthy volunteers information). In clinical studies of surgical patients, these reactions were reported as uncommon, and in post-marketing reports the frequency is unknown.
These reactions ranged from isolated skin reactions to severe systemic reactions (such as anaphylaxis, anaphylactic shock) and occurred in patients who had no prior exposure to sugammadex.
Symptoms associated with these reactions may include: flushing, urticaria, erythematous rash, (severe) hypotension, tachycardia, tongue swelling, pharyngeal swelling, bronchospasm, and obstructive pulmonary events. Severe hypersensitivity reactions may be fatal.
In post-marketing reports, hypersensitivity to sugammadex and to the sugammadex-rocuronium complex has been observed.

Respiratory complications related to anesthesia:
Respiratory complications related to anesthesia included resistance against the endotracheal tube, coughing, mild resistance to intubated breathing, emergence reaction during surgery, coughing during the anesthetic procedure or during surgery, or patient spontaneous breathing related to the anesthetic procedure.

Anesthesia-related complications:
Anesthesia-related complications indicating restoration of neuromuscular function include limb or body movement, or coughing during the anesthetic or surgical procedure, grimacing, or endotracheal tube biting. See SmPC, section 4.4 "light anesthesia".

Procedure-related complications:
Procedure-related complications included cough, tachycardia, bradycardia, movement, and increased heart rate.

Marked bradycardia:
In post-marketing experience, isolated cases of marked bradycardia and bradycardia with cardiac arrest have been observed a few minutes after administration of sugammadex (see SmPC, section 4.4).

Reappearance of neuromuscular block:
In clinical studies of subjects treated with rocuronium or vecuronium, in which sugammadex was administered at the dose indicated for deep neuromuscular block (N=2,022), an incidence of 0.20% of reappearance of neuromuscular block was observed based on neuromuscular monitoring or clinical evidence (see SmPC, section 4.4).

Healthy volunteers information:
A randomized, double-blind study evaluated the incidence of drug hypersensitivity reactions in healthy volunteers who received 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 adjudicated incidence of 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 adjudicated case of 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 repeated doses of sugammadex.
In a previous study with a similar design, there were three adjudicated cases of anaphylaxis, all after sugammadex 16 mg/kg (incidence 2.0%).
In the pooled Phase 1 clinical trial database, adverse events considered common (≥ 1/100, < 1/10) or very common (≥ 1/10) and more frequent in subjects treated with sugammadex compared to placebo included 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
Patients with history of pulmonary complications:
In post-marketing data and in a dedicated clinical study conducted in patients with a history of pulmonary complications, bronchospasm was reported as an adverse event possibly related to the medicinal product. As with all patients with a history of pulmonary complications, physicians should be aware of the possible occurrence of bronchospasm.

Paediatric population
In studies of paediatric patients from birth to 17 years of age, the safety profile of sugammadex (up to 4 mg/kg) was generally similar to that observed in adults.

Patients with pathological obesity
In a dedicated clinical study in patients with pathological obesity, the safety profile was generally similar to that observed in adult patients in pooled Phase 1 to 3 studies (see Table 2).

Patients with severe systemic disease
In a study of patients classified as American Society of Anesthesiologists (ASA) Class 3 or 4 (patients with severe systemic disease or patients with severe systemic disease representing a constant life threat), the adverse reaction profile in ASA Class 3 and 4 patients was generally similar to that in adult patients in pooled Phase 1 to 3 studies (see Table 2); see SmPC, section 5.1.

Overdose
One case of accidental overdose with a dose of 40 mg/kg body weight was reported in clinical trials, which did not result in significant adverse reactions. In a human tolerability study, sugammadex was administered at doses up to 96 mg/kg body weight. No dose-related adverse events or serious adverse events were reported.
Sugammadex can be removed by haemodialysis using a high-flux filter, but not with a low-flux filter. Based on clinical studies, plasma concentrations of sugammadex are reduced by up to 70% after a dialysis session lasting 3 to 6 hours.

List of excipients
Hydrochloric acid 3.7% (to adjust pH) and/or sodium hydroxide (to correct pH)
Water for injections

Shelf life
3 years
After first opening and dilution, chemical and physical in-use stability has been demonstrated for 48 hours at a temperature between 2 °C and 25 °C. From a microbiological point of view, the diluted medicinal product should be used immediately. If not used immediately, in-use storage conditions and duration prior to use are the responsibility of the user; normally not exceeding 24 hours at 2 °C to 8 °C, unless dilution has been carried out under validated aseptic and controlled conditions.

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

Special precautions for disposal and handling
Sugammadex Mylan may be injected into an intravenous infusion line containing 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%), Ringer's lactate solution, Ringer's 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 Sugammadex Mylan and other medicinal products.

Use in the paediatric population
For paediatric patients, Sugammadex Mylan may be diluted with sodium chloride 9 mg/mL (0.9%) to a concentration of 10 mg/mL (see SmPC, section 6.3).