Sugammadex baxter: detailed information

Package leaflet: Information for the user

Sugammadex Baxter, 100 mg/ml, solution for injection
sugammadex
Please read all of this leaflet carefully before the medicine is administered, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your anaesthetist or doctor.
If you experience any side effects, including any not listed in this leaflet, tell your anaesthetist or another doctor immediately. See section 4.

Contents of the leaflet

What Sugammadex Baxter is and what it is used for
Important information before receiving Sugammadex Baxter
How Sugammadex Baxter is given
Possible side effects
How to store Sugammadex Baxter
Contents of the pack and other information

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

What Sugammadex Baxter is
Sugammadex Baxter contains the active substance sugammadex. Sugammadex is considered a
selective relaxant binding agent because it acts only on specific muscle relaxants — rocuronium bromide or vecuronium bromide.

Why Sugammadex Baxter is used
During certain types of surgery, the patient's muscles must be completely relaxed to allow the surgeon easier access. For this purpose, muscle relaxants are administered during general anaesthesia. These are known as neuromuscular blocking agents, and include rocuronium bromide and vecuronium bromide.
Since these drugs also relax the respiratory muscles, assisted ventilation (mechanical ventilation) is required during and after surgery until the patient can breathe independently again.
Sugammadex Baxter is used to accelerate the recovery of muscle function after surgery, enabling the patient to breathe independently sooner. It works by binding to rocuronium bromide or vecuronium bromide in the body.
The medicine can be used in adults when rocuronium bromide or vecuronium bromide has been administered.
It can also be used in newborns, infants, young children, children, and adolescents (from birth up to 17 years of age) when rocuronium bromide has been given.

2. Important information before administration of Sugammadex Baxter

When not to administer Sugammadex Baxter

If the patient is allergic to sugammadex or any of the other ingredients of this medicine (listed in section 6). → In such a case, inform the anaesthesiologist immediately.

Warnings and precautions
Before administration of Sugammadex Baxter, discuss the following with the anaesthesiologist:

If the patient currently has or has previously had kidney diseases. This is important because sugammadex is eliminated from the body via the kidneys.
If the patient currently has or has previously had liver diseases.
If the patient has fluid retention in the body (oedema).
If the patient has diseases known to increase the risk of bleeding (coagulation disorders) or is taking anticoagulant medicines.

Sugammadex Baxter and other medicines
→ Inform the anaesthesiologist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. Sugammadex Baxter may affect the action of other medicines, or other medicines may affect the action of Sugammadex Baxter.
Some medicines reduce the effectiveness of Sugammadex Baxter
→ It is particularly important to inform the anaesthesiologist if the following medicines have been taken recently:

toremifene (used in the treatment of breast cancer).
fusidic acid (an antibiotic).

Sugammadex Baxter may affect the effectiveness of hormonal contraceptives

Sugammadex Baxter may reduce the effectiveness of hormonal contraceptives, including oral contraceptive pills, vaginal rings, implants, or hormone-releasing intrauterine devices, because it reduces the amount of the progestogen hormone delivered. The amount of progestogen lost due to administration of Sugammadex Baxter is approximately equivalent to missing one oral contraceptive pill. → If taking an oral contraceptive pill on the same day that Sugammadex Baxter is administered, follow the instructions for missed pill provided in the leaflet of the hormonal contraceptive. → If using other hormonal contraceptives (such as a vaginal ring, implant, or hormone-releasing intrauterine device), an additional non-hormonal contraceptive method (e.g. condoms) should be used for the next 7 days, and the recommendations in the leaflet of the specific contraceptive product should be followed.

Effect on blood test results
Sugammadex Baxter usually does not affect laboratory test results. However, it may influence blood test results for a hormone called progesterone. Consult the doctor if progesterone blood levels need to be measured on the same day that Sugammadex Baxter is administered.

Pregnancy and breastfeeding
→ Inform the anaesthesiologist if the patient is pregnant or may be pregnant, or if she is breastfeeding. Sugammadex Baxter may still be used in pregnant patients, but this should be discussed with the doctor.
It is unknown whether sugammadex passes into human milk. The anaesthesiologist will help the patient decide whether to discontinue breastfeeding or to refrain from administering sugammadex, taking into account the benefits of breastfeeding for the child and the benefits of treatment with Sugammadex Baxter for the mother.

Driving and operating machinery
Sugammadex Baxter has no known effect on the ability to drive or operate machinery.

Sugammadex Baxter contains sodium
The medicine contains up to 9.2 mg of sodium (the main component of table salt) per millilitre. This corresponds to 0.5% of the maximum recommended daily dietary intake of sodium for adults.

3. How Sugammadex Baxter is administered

Sugammadex Baxter will be administered to the patient by an anaesthesiologist or under the supervision of an anaesthesiologist.
Dosage
The anaesthesiologist will adjust the dose of sugammadex based on:

the patient's body weight
the dose of neuromuscular blocking agent used. The usual dose is 2–4 mg/kg body weight in patients of all ages. If rapid reversal of neuromuscular blockade is required, a dose of 16 mg/kg body weight may be given in adults.

How Sugammadex Baxter is administered
Sugammadex Baxter will be administered by an anaesthesiologist as a single intravenous injection through an intravenous line.
If more Sugammadex Baxter has been administered than recommended
Since the anaesthesiologist closely monitors the patient's condition, overdose of Sugammadex Baxter is unlikely. Nevertheless, if such an event occurs, no problems are expected to arise.
If you have any further questions regarding the use of this medicine, please consult the anaesthesiologist or another doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
If these adverse reactions occur during anaesthesia, they will be noticed and treated by the anaesthetist.

Common adverse reactions (may occur in up to 1 in 10 people)

Coughing
Breathing difficulties, including coughing or movement, such as during waking up or taking a breath
Light anaesthesia – the patient may start to wake up from deep sleep and require additional anaesthetic. This may result in movement or coughing towards the end of surgery
Intraoperative complications, such as changes in heart rate, coughing or movement
Reduced blood pressure related to the surgical procedure

Uncommon adverse reactions (may occur in up to 1 in 100 people)

Shortness of breath due to bronchial muscle spasm (bronchospasm) in patients with a history of lung disease
Allergic reactions (hypersensitivity to the medicine), such as rash, redness of the skin, swelling of the tongue and (or) throat, shortness of breath, changes in blood pressure or heart rhythm, sometimes leading to severe drop in blood pressure. Severe allergic reactions or allergic-like reactions may be life-threatening. Allergic reactions have been reported more frequently in healthy, awake volunteers
Return of muscle weakness after surgery

Frequency not known

After administration of Sugammadex Baxter, severe cases of bradycardia, including slowing of the heart rate up to cardiac arrest, are possible

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform the anaesthetist or another doctor.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Sugammadex Baxter

The medicine will be stored by healthcare personnel.
Keep this medicine out of 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 the stated month.
Store the vial in the outer packaging to protect it from light.
After first opening and dilution, store at a temperature between 2°C and 8°C and use within 24 hours.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Sugammadex Baxter contains

The active substance is sugammadex. 1 ml of injection 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 ingredients are: water for injections, hydrochloric acid 3.2% (for pH adjustment) and (or) sodium hydroxide (for pH adjustment).

What Sugammadex Baxter looks like and contents of the pack
Sugammadex Baxter is a clear, colourless to slightly yellow-brown solution for injection.
It may be available in two different pack sizes containing either 10 vials of 2 ml or 10 vials of 5 ml of solution for injection.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Baxter Holding B.V.
Kobaltweg 49,
3542 CE Utrecht
The Netherlands
Manufacturer
Solupharm Pharmazeutische Erzeugnisse GmbH
Industriestrasse 3
34212 Melsungen
Germany
For further information, contact the local representative of the Marketing Authorisation Holder:
Baxter Polska Sp. z o.o
+48 22 488 37 77
This medicinal product is authorised in the European Economic Area countries under the following names:
Country Product Name
Ireland Sugammadex 100 mg/ml Solution for Injection
Czech Republic Sugammadex Baxter
Denmark Sugammadex Baxter
Austria Sugammadex Baxter 100 mg/ml Injektionslösung
Germany Sugammadex Baxter 100 mg/ml Injektionslösung
Greece Sugammadex/Baxter
Spain Sugammadex Baxter 100 mg/ml solución inyectable EFG
Finland Sugammadex Baxter 100 mg/ml injektioneste, liuos
France Sugammadex Baxter 100 mg/ml, solution injectable
Italy Sugammadex Baxter
Norway Sugammadex Baxter
Belgium Sugammadex Baxter 100 mg/ml solution injectable
Poland Sugammadex Baxter
Portugal Sugamadex Baxter
Romania Sugammadex Baxter 100 mg/ml soluție injectabilă
Slovenia Sugamadeks Baxter 100 mg/ml raztopina za injiciranje
Sweden Sugammadex Baxter
The Netherlands Sugammadex Baxter 100 mg/ml oplossing voor injectie

Information intended exclusively for healthcare professionals:

For detailed information, refer to the Summary of Product Characteristics (SmPC) for Sugammadex Baxter.

Indications and dosage

Reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults.

Children and adolescents: Sugammadex is recommended for routine reversal of rocuronium-induced blockade in children and adolescents from birth to 17 years of age.

Sugammadex should be administered only by an anaesthesiologist or under their supervision.

Appropriate neuromuscular monitoring techniques are recommended to monitor the reversal of neuromuscular blockade (see SmPC, section 4.4).

Adults

Routine reversal of blockade:
Following blockade induced by rocuronium or vecuronium, when recovery has reached at least 1–2 post-tetanic counts (PTC), a dose of 4 mg/kg body weight (bw) of sugammadex is recommended. The median time to return of the T₁/T₄ ratio to 0.9 is approximately 3 minutes (see SmPC, section 5.1).

Following blockade induced by rocuronium or vecuronium, when spontaneous recovery has progressed to the reappearance of T₁, a dose of 2 mg/kg bw of sugammadex is recommended. The median time to return of the T₁/T₄ ratio to 0.9 is approximately 2 minutes (see SmPC, section 5.1).

Use of the recommended doses for routine reversal will result in slightly shorter median times to T₁/T₄ ratio recovery to 0.9 for rocuronium-induced neuromuscular blockade compared to vecuronium (see SmPC, section 5.1).

Immediate reversal of rocuronium-induced blockade:
If immediate reversal of rocuronium-induced blockade is clinically required, a dose of 16 mg/kg bw of sugammadex is recommended. When sugammadex 16 mg/kg bw is administered 3 minutes after a bolus dose of rocuronium bromide 1.2 mg/kg bw, the median time to return of the T₁/T₄ ratio to 0.9 is expected to be approximately 1.5 minutes (see SmPC, section 5.1).

There are no data supporting the use of sugammadex for immediate reversal of vecuronium-induced blockade.

Re-administration of sugammadex:
In exceptional cases of recurrence of neuromuscular blockade after surgery (see SmPC, section 4.4), after an initial dose of 2 mg/kg bw or 4 mg/kg bw, a repeat dose of 4 mg/kg bw of sugammadex is recommended. After administration of a second dose of sugammadex, patients should be carefully monitored to ensure full recovery of neuromuscular transmission.

Renal impairment:
Sugammadex is not recommended in patients with severe renal impairment (including patients requiring dialysis (CrCl < 30 mL/min)) (see SmPC, section 4.4).

Obese patients:
In obese patients, including morbidly obese patients (body mass index [BMI] ≥ 40 kg/m²), the dose of sugammadex should be based on actual body weight. Follow adult dosing recommendations.

Children and adolescents (from birth to 17 years)

Sugammadex Baxter 100 mg/mL may be diluted to a concentration of 10 mg/mL to improve dosing accuracy in children and adolescents (see SmPC, section 6.6).

Routine reversal of blockade:
To reverse rocuronium-induced blockade when recovery has reached at least 1–2 on the post-tetanic count (PTC) scale, a dose of 4 mg/kg bw of sugammadex is recommended.

To reverse rocuronium-induced blockade at the reappearance of T₁, a dose of 2 mg/kg bw is recommended (see SmPC, section 5.1).

Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in SmPC, section 6.1.

Special warnings and precautions for use

As is standard anaesthetic practice following neuromuscular blockade, patients should be closely monitored postoperatively for unexpected events, including recurrence of neuromuscular blockade.

Monitoring of respiratory function during reversal:
Mechanical ventilation is mandatory until spontaneous respiratory function returns following reversal of neuromuscular blockade. Even if neuromuscular blockade is fully reversed, other drugs used in the pre- and postoperative period may depress respiratory function, and thus mechanical ventilation may still be required.

If neuromuscular blockade recurs after extubation, appropriate ventilation should be provided.

Recurrence of neuromuscular blockade:
In clinical studies involving patients receiving rocuronium or vecuronium, when sugammadex was administered at doses based on the degree of neuromuscular blockade, recurrence of neuromuscular blockade was observed at a frequency of 0.20%, 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. This is not recommended (see SmPC, section 4.2 and section 4.8).

Effect on haemostasis:
In a volunteer study, sugammadex at doses of 4 mg/kg bw and 16 mg/kg bw caused mean maximum prolongation of activated partial thromboplastin time (aPTT) by 17% and 22%, and of prothrombin time/international normalized ratio [PT (INR)] by 11% and 22%, respectively. This limited mean prolongation of aPTT and PT (INR) was transient (≤ 30 minutes). Based on the clinical database (n=3519) and results from a study in 1184 patients undergoing hip fracture surgery/hip arthroplasty, no clinically relevant effect of sugammadex 4 mg/kg bw, administered alone or in combination with anticoagulants, on the incidence of peri- and postoperative bleeding complications has been observed.

In vitro studies have shown pharmacodynamic interactions (prolongation of aPTT and PT) with vitamin K antagonists, unfractionated heparin, low molecular weight heparins, rivaroxaban, and dabigatran. In patients receiving routine postoperative anticoagulant prophylaxis, such pharmacodynamic interactions are not clinically relevant. Caution should be exercised when considering the use of sugammadex in patients receiving anticoagulant therapy due to pre-existing or concomitant disease.

Increased bleeding risk cannot be excluded in the following patients:

with congenital deficiency of vitamin K-dependent clotting factors;
with pre-existing coagulopathies;
receiving coumarin derivatives and with INR (International Normalized Ratio) above 3.5;
receiving anticoagulant therapy who are to receive sugammadex at a dose of 16 mg/kg bw.

If medical necessity requires administration of sugammadex to these patients, the anaesthesiologist must weigh the benefits against the potential risk of bleeding complications, taking into account the patient's history of bleeding episodes and the type of planned procedure. If sugammadex is administered to these patients, monitoring of haemostasis and coagulation parameters is recommended.

Intervals to wait before re-administering neuromuscular blocking agents after reversal by sugammadex:

Table 1: Re-administration of rocuronium or vecuronium after routine reversal (sugammadex at doses up to 4 mg/kg bw):

Minimum waiting time	Neuromuscular blocking agent and dose to be administered
5 minutes	rocuronium at a dose of 1.2 mg/kg body weight
4 hours	rocuronium at a dose of 0.6 mg/kg body weight or vecuronium at a dose of 0.1 mg/kg body weight

After re-administration of rocuronium at a dose of 1.2 mg/kg body weight within 30 minutes following sugammadex administration, the onset of neuromuscular blockade may be prolonged to approximately 4 minutes, and the duration of this blockade may be shortened to approximately 15 minutes.

Based on a PK model, in patients with mild or moderate renal impairment, after routine reversal of neuromuscular blockade by sugammadex, it is recommended to wait 24 hours before re-administering rocuronium at a dose of 0.6 mg/kg body weight or vecuronium at a dose of 0.1 mg/kg body weight. If the waiting period must be shorter, to induce a new neuromuscular blockade, rocuronium should be administered at a dose of 1.2 mg/kg body weight.

Re-administration of rocuronium or vecuronium after immediate reversal of blockade (sugammadex at a dose of 16 mg/kg body weight):

In very rare cases where such management may be necessary, a waiting period of 24 hours is recommended.

If neuromuscular blockade is required before the recommended waiting time has elapsed, a nonsteroidal neuromuscular blocking agent should be used. A depolarizing neuromuscular blocking agent may have a slower onset than expected, as a significant proportion of postsynaptic nicotinic receptors may still be occupied by the neuromuscular blocking agent.

Renal impairment:

Sugammadex is not recommended in patients with severe renal impairment, including those requiring dialysis therapy (see SmPC, section 5.1).

Light anaesthesia:

When reversal of neuromuscular blockade was performed during anaesthesia in clinical trials—i.e., when the purpose was to study reversal—signs of light anaesthesia (movement, coughing, facial grimacing, and biting the endotracheal tube) were sometimes observed.

When reversing neuromuscular blockade during anaesthesia, additional doses of anaesthetic and/or opioid should be administered as clinically indicated.

Significant bradycardia:

In rare cases, significant bradycardia has been observed within minutes after administration of sugammadex for reversal of neuromuscular blockade. Occasionally, bradycardia may lead to cardiac arrest (see SmPC, section 4.8). Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. In case of clinically significant bradycardia, anticholinergic drugs such as atropine should be administered.

Hepatic impairment:

Sugammadex is not metabolized or excreted by the liver; therefore, studies in patients with hepatic failure have not been conducted. Extreme caution should be exercised when administering sugammadex to patients with severe hepatic impairment. If hepatic dysfunction is associated with coagulopathy, refer to information regarding the product's effect on hemostasis.

Intensive care units:

The use of sugammadex has not been studied in intensive care units in patients receiving rocuronium or vecuronium.

Use for reversal of blockade induced by neuromuscular blocking agents other than rocuronium or vecuronium:

Sugammadex should not be used to reverse blockade induced by nonsteroidal neuromuscular blocking agents, such as succinylcholine or benzylisoquinolinium compounds.

Sugammadex should not be used to reverse blockade induced by steroidal neuromuscular blocking agents other than rocuronium or vecuronium, as there are no data on efficacy and safety for such compounds. Limited data are available on reversal of pancuronium-induced blockade, but use of sugammadex in such situations is not recommended.

Delayed reversal:

Conditions associated with reduced blood flow, such as cardiovascular disease, advanced age (see SmPC, section 4.2, time to recovery in elderly patients), or edematous states (e.g., severe hepatic impairment), may be associated with a longer time required for recovery of neuromuscular transmission.

Hypersensitivity reactions to the medicinal product:

Clinicians should be prepared for the possibility of hypersensitivity reactions to the medicinal product (including anaphylactic reactions) and should take appropriate precautionary measures (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 sodium intake of 2 g recommended by WHO for adults.

Interactions with other medicinal products and other forms of interactions

The information in this section is based on binding affinity between sugammadex and other drugs, non-clinical experience, clinical studies, and simulations using a model incorporating the pharmacodynamic effects of neuromuscular blocking agents and pharmacokinetic interactions between neuromuscular blocking agents and sugammadex. Based on these data, clinically significant pharmacodynamic interactions with other drugs are not expected, except as follows:

For toremifene and fusidic acid, displacement interactions cannot be excluded (clinically significant uptake-related interactions are not expected).

For hormonal contraceptives, clinically significant uptake-related interactions cannot be excluded (displacement-related interactions are not expected).

Interactions potentially affecting the efficacy of sugammadex (displacement interactions):

After administration of certain medicinal products following sugammadex, displacement of rocuronium or vecuronium from the sugammadex complex may theoretically occur. This may result in recurrence of neuromuscular blockade. In such cases, the patient must be ventilated. If an infusion is ongoing, administration of the medicinal product causing the displacement reaction should be discontinued. When a displacement interaction is anticipated, patients should be carefully monitored for recurrence of neuromuscular blockade (for approximately 15 minutes) after intravenous administration of another medicinal product within 7.5 hours after sugammadex administration.

Toremifene:

Toremifene has relatively high affinity for sugammadex and may reach relatively high plasma concentrations, potentially leading to displacement of vecuronium or rocuronium from the sugammadex complex. Therefore, physicians should be aware that the time to recovery of the T/T ratio to 0.9 may be prolonged in patients who have received toremifene on the day of surgery.

Intravenous administration of fusidic acid:

Preoperative use of fusidic acid may slightly prolong the time to recovery of the T/T ratio to 0.9. Recurrence of neuromuscular blockade in the postoperative period is not expected, as fusidic acid infusion lasts several hours and blood test results are visible after 2–3 days. For re-administration of sugammadex, see SmPC, section 4.2.

Interactions potentially affecting the efficacy of other medicinal products (uptake interactions):

After administration of sugammadex, certain medicinal products may be less effective due to reduced plasma concentrations (free fraction). If such a situation occurs, it is recommended to consider re-administering the medicinal product, using a therapeutically equivalent alternative (preferably from a different chemical class), and/or applying non-pharmacological interventions.

Hormonal contraceptives:

An interaction between sugammadex at a dose of 4 mg/kg body weight and progestogens has been demonstrated, leading to reduced progestogen exposure (34% AUC), similar to the reduction seen when the daily dose of a hormonal contraceptive is taken 12 hours later, potentially resulting in reduced efficacy. For estrogens, this effect appears to be less pronounced. Therefore, administration of sugammadex as a bolus is considered equivalent to missing a daily dose of oral hormonal contraceptives (both combined hormonal contraceptives and progestogen-only contraceptives). Refer to the recommendations in the package leaflet regarding management of missed contraceptive doses when an oral contraceptive has been taken on the same day as sugammadex administration.

For hormonal contraceptives not administered orally, an additional non-hormonal contraceptive method should be used for the next 7 days, and the recommendations in the contraceptive product's package leaflet should be consulted.

Interactions resulting from prolonged action of rocuronium or vecuronium:

If medicinal products that may enhance neuromuscular blockade are used in the postoperative period, particular attention should be paid to the possibility of recurrence of neuromuscular blockade. Refer to the list of specific medicinal products that potentiate neuromuscular blockade provided in the package leaflet of rocuronium or vecuronium. In case of recurrence of neuromuscular blockade, mechanical ventilation and re-administration of sugammadex may be necessary (see SmPC, section 4.2).

Effects on fertility, pregnancy and lactation

Pregnancy

There are no clinical data on the use of sugammadex in pregnant women.

Animal studies have not shown direct or indirect harmful effects on pregnancy, embryo/fetal development, parturition, or postnatal development.

Caution should be exercised when administering sugammadex to pregnant women.

Breastfeeding

It is not known whether sugammadex passes into human milk. Animal studies confirm excretion of sugammadex into milk. Oral absorption of cyclodextrins is generally low, and no effect on the breastfed infant is expected after a single dose of sugammadex administered to a breastfeeding woman.

A decision must be made whether to discontinue breastfeeding or to discontinue sugammadex therapy, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the mother.

Fertility

The effect of sugammadex on fertility has not been studied in humans. Animal studies have not shown harmful effects on fertility.

Adverse reactions

Summary of safety profile

Sugammadex Baxter is administered to patients undergoing surgical procedures who are also receiving neuromuscular blocking agents and anaesthetics. Therefore, it is difficult to establish a causal relationship for adverse reactions.

The most frequently reported adverse reactions in patients undergoing surgical procedures are cough, anaesthesia-related respiratory complications, anaesthesia-related complications, procedure-related hypotension, and procedure-related complications (Common (≥ 1/100 to < 1/10)).

Table 2: Tabulated list of adverse reactions

The safety of sugammadex was evaluated based on a pooled safety database from Phase I–III studies involving 3519 individual patients. The following adverse reactions were reported in placebo-controlled trials in which patients received anaesthetics and/or neuromuscular blocking agents (1078 patients received sugammadex, 544 patients received placebo):

[Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000)]

System organ classes	Frequency	Adverse reactions (Preferred terms)
Immune system disorders	Uncommon	Drug hypersensitivity reactions (see SmPC, section 4.4)
Respiratory, thoracic and mediastinal disorders	Common	Cough
Injury, poisoning and procedural complications	Common	Respiratory complications associated with anaesthesia Complications associated with anaesthesia (see SmPC, section 4.4) Procedure-related hypotension Post-procedural complications

Description of selected adverse reactions

Hypersensitivity reactions to the medicinal product:
Hypersensitivity reactions, including anaphylaxis, have been observed in some patients and volunteers (information regarding volunteers is provided below under "Information on healthy volunteers"). In clinical trials involving surgical patients, these reactions were reported infrequently; in post-marketing surveillance, the frequency of hypersensitivity reactions is unknown.
These reactions varied from local skin reactions to severe systemic reactions (i.e., anaphylaxis, anaphylactic shock) and occurred in patients who had not previously been treated with sugammadex.
Symptoms associated with these reactions included: hot flushes, urticaria, erythematous rash, (severe) hypotension, tachycardia, tongue swelling, throat swelling, bronchospasm, and episodes of pulmonary obstruction. Severe hypersensitivity reactions may be fatal.
Post-marketing reports have documented hypersensitivity to both sugammadex and the sugammadex-rocuronium complex.

Respiratory complications related to anaesthesia:
Respiratory complications related to anaesthesia included coughing on the endotracheal tube, coughing, mild coughing, emergence during surgery, coughing during anaesthesia or surgery, or spontaneous patient respiration associated with anaesthetic procedure.

Complications related to anaesthesia:
Anaesthesia-related complications indicating return of neuromuscular function include limb or body movements, coughing during the anaesthetic procedure or surgery, facial grimacing, or biting the endotracheal tube. See SmPC, section 4.4, light anaesthesia.

Procedure-related complications:
Procedure-related complications included cough, tachycardia, bradycardia, movement, and rapid heartbeat.

Marked bradycardia:
In the post-marketing period, rare cases of marked bradycardia and bradycardia with circulatory arrest have been observed within minutes after administration of sugammadex (see SmPC, section 4.4).

Recurrence of neuromuscular blockade:
In clinical trials involving patients treated with rocuronium or vecuronium, where sugammadex was administered at a dose dependent on the degree of neuromuscular blockade (n=2022), recurrence of neuromuscular blockade was observed at a frequency of 0.20%, based on neuromuscular transmission monitoring or clinical evidence (see SmPC, section 4.4).

Information on healthy volunteers:
In a randomized, double-blind, placebo-controlled trial, the incidence of hypersensitivity reactions to the medicinal product was evaluated in healthy volunteers who received no more than 3 doses of placebo (n=76), sugammadex 4 mg/kg body weight (n=151), or sugammadex 16 mg/kg body weight (n=148). Suspected hypersensitivity cases were adjudicated by a committee in a blinded manner. The incidence of confirmed hypersensitivity reactions in the placebo, sugammadex 4 mg/kg, and sugammadex 16 mg/kg groups was 1.3%, 6.6%, and 9.5%, respectively. No cases of anaphylaxis were reported after placebo or sugammadex 4 mg/kg. Following the first dose of sugammadex 16 mg/kg, a single case of confirmed anaphylaxis occurred (incidence 0.7%). No increased frequency or severity of hypersensitivity reactions was observed with repeated administration of sugammadex.
In an earlier study with a similar design, three confirmed cases of anaphylaxis occurred, all after administration of sugammadex 16 mg/kg (incidence 2.0%).

In the pooled Phase 1 database, adverse reactions occurring commonly (≥ 1/100 to < 1/10) or very commonly (≥ 1/10) and more frequently in patients receiving sugammadex than in placebo recipients include: taste disturbances (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 specific patient groups

Patients with lung disease:
In post-marketing data and in one clinical trial specifically conducted in patients with a history of pulmonary complications, bronchospasm has been reported as an adverse event possibly related to treatment. The possibility of bronchospasm should be considered in all patients with a history of prior pulmonary complications.

Children and adolescents
In studies involving children and adolescents aged from birth to 17 years, the safety profile of sugammadex (up to 4 mg/kg body weight) was generally similar to that observed in adults.

Morbidly obese patients
In a dedicated clinical trial in morbidly obese patients, the safety profile was generally similar to that observed in adult patients in pooled Phase 1–3 trials (see Table 2).

Patients with severe systemic disease
In a study involving patients classified according to the American Society of Anesthesiologists (ASA) classification as ASA Class 3 or 4 (patients with severe systemic disease or severe systemic disease constituting a constant threat to life), the adverse reaction profile in these patients was generally similar to that in adult patients in combined Phase 1 to 3 trials (see Table 2). See SmPC, section 5.1.

Overdose
One case of accidental overdose with 40 mg/kg without significant adverse reactions was reported in clinical trials. In a human tolerance study, sugammadex was well tolerated at doses up to 96 mg/kg. No dose-dependent or serious adverse events were reported.
Sugammadex can be removed from the body by hemodialysis using a high-flux filter, but not with a low-flux filter. Based on clinical studies, serum concentrations of sugammadex were reduced by up to 70% after dialysis sessions lasting 3 to 6 hours.

List of excipients
Hydrochloric acid 3.2% (for pH adjustment) and/or sodium hydroxide (for pH adjustment)
Water for injections

Shelf life
4 years
After first opening and dilution, chemical and physical stability during use has been demonstrated for 48 hours at temperatures from 2°C to 25°C. From a microbiological standpoint, the diluted product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration, which should not exceed 24 hours at 2°C to 8°C, unless dilution was performed under controlled and validated aseptic conditions.

Special precautions for storage
Store vials in the outer packaging to protect from light.
Storage conditions after dilution, see SmPC, section 6.3.

Special precautions for disposal and preparation of the medicinal product for use
The medicinal product Sugammadex Baxter should be administered into an intravenous infusion line using the following intravenous solutions: sodium chloride 9 mg/ml (0.9%), glucose 50 mg/ml (5%), sodium chloride 4.5 mg/ml (0.45%), glucose 25 mg/ml (2.5%), lactated Ringer's 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 solution) between administration of Sugammadex Baxter and other medicinal products.

Use in children and adolescents
In children and adolescents, the medicinal product Sugammadex Baxter may be diluted using sodium chloride 9 mg/ml (0.9%) to a concentration of 10 mg/ml (see SmPC, section 6.3).