BRIDION 100 mg/mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bridion 100mg/ml solution for injection

sugammadex

Read all of 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 further questions, ask your anaesthetist or doctor.
• If you get any side effects, talk to your anaesthetist or doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Bridion and what is it used for

What is Bridion

Bridion contains the active substance sugammadex. Bridion is considered a Selective Relaxant Binding Agentas it only works with specific muscle relaxants, rocuronium bromide or vecuronium bromide.

What Bridion is used for

If you have to undergo surgery, your muscles must be completely relaxed, making it easier for the surgeon to perform the operation. For this, you will be given medicines during general anaesthesia to relax your muscles. These are called muscle relaxants, such as rocuronium bromide and vecuronium bromide. Since these medicines also block the respiratory muscles, you will need help breathing (artificial respiration) during and after surgery until you can breathe on your own again.

Bridion is used to speed up the recovery of your muscles after surgery so that you can breathe on your own again sooner. It does this by combining with rocuronium bromide or vecuronium bromide in your body. It can be used in adults when rocuronium bromide or vecuronium bromide is used.

It can be used in newborns, infants, children, and adolescents (from birth to 17 years) when rocuronium bromide is used.

2. What you need to know before you are given Bridion

You should not be given Bridion

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

→ Tell your anaesthetist if this applies to you.

Warnings and precautions

Talk to your anaesthetist before you are given Bridion

• if you have or have had kidney disease. This is important because Bridion is removed from your body by the kidneys.
• if you have or have had liver disease.
• if you have fluid retention (oedema).
• if you have a disease that increases the risk of bleeding (blood coagulation disorders) or are taking anticoagulant medication.

Other medicines and Bridion

→ Tell your anaesthetist if you are taking, have recently taken, or might take any other medicines.

Bridion may affect other medicines or be affected by them.

Some medicines reduce the effect of Bridion

→It is especially important that you tell your anaesthetist if you have recently taken:

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

Bridion may affect hormonal contraceptives

• Bridion may make hormonal contraceptives - such as the "Pill", vaginal ring, implants, or a Hormonal Intrauterine Device (IUD) - less effective because it reduces the amount of progestogen that reaches you. The amount of progestogen lost due to the use of Bridion is approximately the same as when you miss a contraceptive pill.

→ If you are taking the Pillon the same day that you are given Bridion, follow the instructions in case of a missed pill in the pill leaflet.

→ If you are using otherhormonal contraceptives (e.g. vaginal ring, implant, or IUD), you should use a non-hormonal contraceptive method (such as a condom) for the next 7 days and follow the recommendations in the leaflet.

Effects on laboratory tests

In general, Bridion does not affect laboratory tests. However, it may affect the results of a blood test when progesterone levels are measured. Talk to your doctor if your progesterone levels need to be tested on the same day that you receive Bridion.

Pregnancy and breastfeeding

→Tell your anaesthetist if you are pregnant or think you may be pregnant or if you are breastfeeding.

It may still be given to you, but this needs to be discussed beforehand.

It is not known whether sugammadex can pass into breast milk. Your anaesthetist will help you decide whether to stop breastfeeding or avoid treatment with sugammadex, considering the benefit of breastfeeding to the baby and the benefit of Bridion to the mother.

Driving and using machines

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

Bridion contains sodium

This medicine contains up to 9.7 mg of sodium (the main component of cooking/table salt) per ml. This is equivalent to 0.5% of the maximum recommended daily intake of sodium for an adult.

3. How Bridion is given

Bridion will be given to you by your anaesthetist, or under the supervision of your anaesthetist.

Dose

Your anaesthetist will calculate the dose of Bridion you need based on:

• your weight
• the amount of muscle relaxant that is still affecting you.

The usual dose is 2-4 mg per kg of body weight for patients of any age. A dose of 16 mg/kg may be used in adults if urgent recovery of muscle relaxation is needed.

How Bridion is given

Bridion will be given to you by your anaesthetist. It is injected once into a vein.

If you are given too much Bridion

Since your anaesthetist will be carefully monitoring the situation, it is unlikely that you will be given too much Bridion. But even if this happens, it is unlikely to cause any problems.

If you have any further questions on the use of this medicine, ask your anaesthetist or doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If these side effects occur while you are under anaesthesia, it will be your anaesthetist who detects and treats them.

Common (may affect up to 1 in 10 people)

• Cough
• Respiratory difficulties that may include cough or movements as if waking up or taking a breath
• Light anaesthesia – you may start to wake up, so you may need more anaesthetic. This may cause you to move or cough at the end of the operation
• Complications during the procedure, such as changes in heart rate, cough, or movement
• Decrease in blood pressure due to surgery

Uncommon (may affect up to 1 in 100 people)

• Difficulty breathing due to muscle spasms in the airways (bronchospasm) that occur in patients with a history of lung problems
• Allergic reactions (hypersensitivity to medicines) - such as rash, skin redness, swelling of your tongue and/or pharynx, difficulty breathing, changes in blood pressure or heart rate, which sometimes result in a severe drop in blood pressure. Allergic reactions or severe allergic reactions can be life-threatening

Allergic reactions were reported more frequently in healthy conscious volunteers

• Reappearance of muscle relaxation after surgery

Frequency not known

• When Bridion is given, a significant slowing of the heart can occur, which can even lead to cardiac arrest

Reporting of side effects

If you experience any side effects, talk to your anaesthetist or doctor, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Bridion

Storage will be the responsibility of healthcare professionals.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label after “EXP”. The expiry date refers to the last day of the month shown.

Store below 30°C. Do not freeze. Keep the vial in the outer packaging to protect it from light.

Once opened and diluted, store at 2-8°C and use within 24 hours.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Bridion

• The active substance is sugammadex.

Each ml of injectable solution contains sugammadex sodium equivalent to 100 mg of sugammadex.

Each 2 ml vial contains sugammadex sodium equivalent to 200 mg of sugammadex.

Each 5 ml vial contains sugammadex sodium equivalent to 500 mg of sugammadex.

• The other ingredients are water for injectable preparations, hydrochloric acid 3.7%, and/or sodium hydroxide.

Appearance and Container Content of the Product

Bridion is a clear, colorless to slightly yellowish injectable solution.

It is available in two different container sizes, 10 vials of 2 ml or 10 vials of 5 ml of injectable solution.

Only some container sizes may be marketed.

For further information, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:<{MM/AAAA}><{month YYYY}>.

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

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This information is intended only for healthcare professionals:

For detailed information, refer to the Summary of Product Characteristics (SPC) of BRIDION.

Therapeutic Indications and Dosage

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

For the pediatric population: sugammadex is only recommended for use in pediatric patients from birth to 17 years for routine reversal of rocuronium-induced blockade.

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

Appropriate neuromuscular monitoring technique is recommended to control neuromuscular blockade recovery (see SPC, section 4.4).

Adults

Routine reversal:

A dose of 4 mg/kg sugammadex is recommended if recovery has reached 1-2 post-tetanic counts (PTC) after rocuronium or vecuronium-induced blockade. The median time to recover a T4/T1 ratio to 0.9 is approximately 3 minutes (see SPC, section 5.1).

A dose of 2 mg/kg sugammadex is recommended if spontaneous recovery has occurred to at least the reappearance of T2 after rocuronium or vecuronium-induced blockade. The median time to recover a T4/T1 ratio to 0.9 is approximately 2 minutes (see SPC, section 5.1).

If the recommended doses for routine reversal are used, the median time to recover a T4/T1 ratio to 0.9 for rocuronium will be slightly faster compared to vecuronium-induced neuromuscular blockade (see SPC, section 5.1).

Immediate reversal of rocuronium-induced neuromuscular blockade:

If there is a clinical need for immediate reversal after rocuronium administration, a dose of 16 mg/kg sugammadex is recommended. If 16 mg/kg sugammadex is administered 3 minutes after a bolus dose of 1.2 mg/kg rocuronium bromide, recovery of the T4/T1 ratio to 0.9 can be expected in a median time of approximately 1.5 minutes (see SPC, section 5.1).

No data are available to recommend the use of sugammadex for immediate reversal after vecuronium-induced blockade.

Repetition of the sugammadex dose:

In the exceptional case where postoperative neuromuscular blockade recurs (see SPC, section 4.4) after administration of an initial dose of 2 mg/kg or 4 mg/kg sugammadex, a further dose of 4 mg/kg sugammadex is recommended. After the second dose of sugammadex, the patient should be closely monitored to ensure sustained recovery of neuromuscular function.

Renal Impairment:

The use of sugammadex is not recommended in patients with severe renal impairment (including patients on dialysis) (see SPC, 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 actual body weight. The same dosing recommendations as for adults should be followed.

Pediatric Population (from birth to 17 years)

The Bridion 100 mg/ml injectable solution can be diluted to 10 mg/ml to increase dosing accuracy in the pediatric population (see SPC, section 6.6).

Routine reversal:

A dose of 4 mg/kg sugammadex is recommended for reversal of rocuronium-induced blockade if recovery has reached 1-2 PTC.

A dose of 2 mg/kg is recommended for reversal of rocuronium-induced blockade when T2 reappears (see SPC, section 5.1).

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SPC.

Special Warnings and Precautions for Use

As is customary in post-anesthesia practice after neuromuscular blockade, it is recommended to monitor the patient in the immediate postoperative period for unexpected effects such as recurrence of neuromuscular blockade.

Monitoring of respiratory function during recovery:

Mechanical ventilation is mandatory for patients until adequate spontaneous recovery of respiration occurs after reversal of neuromuscular blockade. Even if recovery from neuromuscular blockade is complete, other medications used in the peri- and postoperative period may depress respiratory function, and mechanical ventilation may still be required.

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

Recurrence of neuromuscular blockade:

In clinical trials with patients treated with rocuronium or vecuronium, where sugammadex was administered using a dose regimen based on the depth of neuromuscular blockade, an incidence of 0.20% for recurrence of neuromuscular blockade was observed, based on neuromuscular monitoring or clinical evidence. The use of lower doses than recommended may result in a higher risk of recurrence of neuromuscular blockade after initial reversal, and is therefore not recommended (see SPC, section 4.2 and section 4.8).

Effect on Hemostasis:

In a study in volunteer patients, doses of 4 mg/kg and 16 mg/kg sugammadex resulted in median maximum prolongations of activated partial thromboplastin time (aPTT) of 17% and 22%, respectively, and prothrombin time (INR) of 11% and 22%, respectively. These median prolongations of aPTT and INR were short-lived (≤ 30 minutes). Based on the clinical database (N = 3519), and a specific study in 1184 patients undergoing hip fracture/surgery for major joint replacement, there was no clinically relevant effect on the incidence of peri- and postoperative bleeding complications with sugammadex 4 mg/kg alone or in combination with anticoagulants.

In in vitro experiments, a pharmacodynamic interaction (prolongation of activated partial thromboplastin time [aPTT] and prothrombin time [PT]) was observed with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran. In patients receiving routine postoperative prophylactic anticoagulation, this pharmacodynamic interaction is not clinically relevant. Caution should be exercised when considering the use of sugammadex in patients receiving anticoagulant treatment for a pre-existing or concomitant condition.

A increased risk of bleeding cannot be ruled out in patients:

• with hereditary deficiencies of vitamin K-dependent coagulation factors;

• with pre-existing coagulopathies;

• treated with coumarin derivatives and with an INR above 3.5;

• using anticoagulants and receiving a dose of 16 mg/kg sugammadex.

If there is a medical need to administer sugammadex to these patients, the anesthesiologist should decide whether the benefits outweigh the potential risk of bleeding complications, taking into account the patient's history of bleeding episodes and the type of surgery planned. It is recommended to monitor hemostasis and coagulation parameters if sugammadex is administered to these patients.

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):

After re-administration of 1.2 mg/kg rocuronium 30 minutes after sugammadex administration, the onset of neuromuscular blockade may be prolonged to approximately 4 minutes, and the duration of neuromuscular blockade may be reduced to approximately 15 minutes.

Based on the pharmacokinetic model, the recommended waiting time for re-administration of 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium after routine reversal with sugammadex in patients with mild or moderate renal impairment should be 24 hours. If a shorter waiting time is required, the dose of rocuronium for a new neuromuscular blockade should be 1.2 mg/kg.

Re-administration of rocuronium or vecuronium after immediate reversal (16 mg/kg sugammadex):

In very rare cases where this may be required, a waiting time of 24 hours is recommended.

If a neuromuscular blocking agent needs to be administered before the recommended waiting time, a non-steroidal neuromuscular blocking agent should be used. The onset of a depolarizing neuromuscular blocking agent may be slower than expected because a substantial fraction of the post-synaptic 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 on dialysis (see SPC, section 5.1).

Superficial Anesthesia:

In clinical trials, in cases where neuromuscular blockade was intentionally reversed during anesthesia, signs of superficial anesthesia (movement, coughing, facial spasms, and sucking on the endotracheal tube) were occasionally observed.

If neuromuscular blockade is reversed while anesthesia is continued, additional doses of anesthetic and/or opioid should be administered as clinically indicated.

Severe Bradycardia:

In rare cases, severe bradycardia has been observed a few minutes after administration of sugammadex for reversal of neuromuscular blockade. In some cases, bradycardia may lead to cardiac arrest (see SPC, section 4.8). Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. If clinically significant bradycardia is observed, treatment with anticholinergics, such as atropine, should be administered.

Hepatic Impairment:

Sugammadex is not metabolized or eliminated by the liver; therefore, specific studies in patients with hepatic impairment have not been conducted. Patients with severe hepatic impairment should be treated with caution. If hepatic impairment is associated with coagulopathy, see the information on the effect on hemostasis.

Use in the Intensive Care Unit (ICU):

Sugammadex has not been investigated in patients who have received rocuronium or vecuronium in the ICU.

Reversal of neuromuscular blockade induced by agents other than rocuronium or vecuronium:

Treatment with sugammadex should not be used to reverse blockade induced by non-steroidal neuromuscular blocking agents such as succinylcholine or benzylisoquinolinium derivatives.

Treatment with sugammadex should not be used for reversal of neuromuscular blockade induced by steroidal neuromuscular blocking agents other than rocuronium or vecuronium, as there are no data on efficacy and safety in these cases. There are limited data on reversal of pancuronium-induced blockade, but the use of sugammadex in this situation is not recommended.

Delayed Recovery:

Situations associated with prolonged circulation times, such as cardiovascular disease, advanced age (see SPC, section 4.2 on recovery time in elderly patients), or edematous states (e.g., severe hepatic impairment), may be associated with longer recovery times.

Drug Hypersensitivity Reactions:

Physicians should be prepared for the possibility of hypersensitivity reactions (including anaphylactic reactions) and should take necessary precautions (see SPC, section 4.8).

Sodium:

This medicinal product contains up to 9.7 mg of sodium per ml, equivalent to 0.5% of the maximum daily intake of 2 g of sodium recommended by the WHO for an adult.

Interaction with Other Medicinal Products and Other Forms of Interaction

The information in this section is based on the binding affinity between sugammadex and other medicinal products, non-clinical experiments, clinical trials, and simulations using a model that takes 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 interactions with other medicinal products are expected, except for the following:

Toremifene and fusidic acid: it cannot be excluded that a pharmacodynamic interaction may occur.

Interaction by displacement (no interactions of clinical relevance are expected).

Hormonal contraceptives: It cannot be excluded that an interaction of clinical relevance may occur (no interactions by displacement are expected).

Interactions that may affect the efficacy of sugammadex (displacement interactions):

Theoretically, the administration of certain medications after treatment with sugammadex may cause displacement of rocuronium or vecuronium from the sugammadex complex, and as a result, a reappearance of neuromuscular blockade may be observed. In this situation, the patient should be administered mechanical ventilation. The administration of the medication causing the displacement should be discontinued if it is administered by infusion. In situations where potential displacement interactions may be anticipated due to the administration of another medication by the parenteral route within 7.5 hours after the administration of sugammadex, patients should be carefully monitored for signs of reappearance of neuromuscular blockade (for approximately 15 minutes).

Toremifene:

In the case of concomitant administration with toremifene, which has a relatively high binding affinity for sugammadex and for which relatively high plasma concentrations may be present, some displacement of rocuronium or vecuronium from the complex with sugammadex may occur. Physicians should be aware that recovery of the T4/T1 ratio to 0.9 may therefore be delayed in patients who have received toremifene on the same day as the surgical intervention.

Intravenous administration of fusidic acid:

The use of fusidic acid in the preoperative phase may cause some delay in the recovery of the T4/T1 ratio to 0.9. No reappearance of neuromuscular blockade is expected in the postoperative phase, since the infusion of fusidic acid lasts several hours and blood levels accumulate over more than 2-3 days. See section 4.2 for re-administration of sugammadex.

Interactions that may affect the efficacy of other medications (capture interactions):

The administration of sugammadex may cause a decrease in the plasma concentrations (free) of certain medications, and therefore their efficacy may decrease. If this situation is observed, the physician should consider re-administering the same medication, administering a therapeutically equivalent medication (preferably belonging to a different chemical class) and/or applying the necessary non-pharmacological interventions.

Hormonal contraceptives:

It is expected that the interaction between sugammadex 4 mg/kg and the progestogen will produce a decrease in exposure to the progestogen (34% of the AUC), similar to the decrease observed if a daily dose of an oral contraceptive is taken with a 12-hour delay, which may lead to a reduction in effectiveness. In the case of estrogens, the effect is expected to be lower. Therefore, the administration of a bolus dose of sugammadex is considered equivalent to missing a daily dose of a steroid oral contraceptive (either combined or with only progestogen). If sugammadex is administered on the same day as an oral contraceptive, reference should be made to the recommendations in case of missed dose of the oral contraceptive prospectus. In the case of non-oral hormonal contraceptives, the patient should use a non-hormonal complementary contraceptive for the next 7 days and follow the recommendations of the product prospectus.

Interactions due to prolonged effect of rocuronium or vecuronium:

If medications that potentiate neuromuscular blockade are used in the postoperative period, special attention should be paid to the possibility of reappearance of neuromuscular blockade. See the prospectuses of rocuronium or vecuronium, which provide a list of specific medications that potentiate neuromuscular blockade. In case of reappearance of neuromuscular blockade, the patient may require mechanical ventilation and repetition of the sugammadex dose (see section 4.2).

Fertility, pregnancy and lactation

Pregnancy

There are no clinical data on the exposure of pregnant women to sugammadex.

Animal studies do not suggest direct or indirect harmful effects on pregnancy, embryofetal development, childbirth, or postnatal development.

Cautiousness should be exercised when administering sugammadex to pregnant women.

Lactation

It is unknown whether sugammadex is excreted in human breast milk. In animal studies, it has been observed that sugammadex is excreted in breast milk. The oral absorption of cyclodextrins is generally low and is not expected to have an effect on the infant after administration of a single dose to the woman during the lactation period.

A decision should be made to discontinue breastfeeding or discontinue treatment, considering the benefit of breastfeeding for the child and the benefit of treatment for the mother.

Fertility

The effects of sugammadex on human fertility have not been investigated. Animal studies to evaluate fertility do not show harmful effects.

Adverse reactions

Summary of safety profile

Bridion was administered concomitantly with neuromuscular blockers and anesthetics in surgical patients. The causality of adverse effects is therefore difficult to assess.

The most frequently reported adverse reactions in surgical patients were cough, respiratory complications due to anesthesia, anesthesia complications, therapeutic procedure hypotension, and procedural complication (Frequent (? 1/100 to <1>

Table2: Table of adverse reactions

The safety of sugammadex has been evaluated in 3,519 unique patients through a combined safety database of Phase I-III. The following adverse reactions were reported in controlled trials with placebo in which patients received anesthesia and/or neuromuscular blockers (1,078 patients exposed to sugammadex versus 544 exposed to placebo):

[Very common (?1/10),common (?1/100 to <1>uncommon (?1/1,000 to <1>rare (?1/10,000 to <1>very rare (<1>

Description of selected adverse reactions

Hypersensitivity reactions:

Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers (for information on volunteers, see later section on healthy volunteers). In clinical trials of surgical patients, these reactions were reported uncommonly, and in post-marketing reports, the frequency is unknown.

These reactions ranged from isolated skin reactions to severe systemic reactions (i.e., anaphylaxis, anaphylactic shock) and have occurred in patients without 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 can be fatal.

In post-marketing reports, hypersensitivity has been observed with both sugammadex and the sugammadex-rocuronium complex.

Anesthesia-related respiratory complications:

Anesthesia-related respiratory complications included spasms related to the end of anesthesia or extubation, cough, mild spasms related to the end of anesthesia or extubation, awakening reaction during surgery, cough during the anesthetic procedure or during surgery, or spontaneous breathing of the patient related to the anesthetic procedure.

Anesthesia complications:

Anesthesia complications, which indicate recovery of neuromuscular function, include movement of a limb or body or cough during anesthesia administration or during surgery, facial spasms or suction on the endotracheal tube. See section 4.4 for superficial anesthesia.

Procedural complication:

Procedural complications included cough, movement, tachycardia, bradycardia, and increased heart rate.

Severe bradycardia:

After marketing, isolated cases of severe bradycardia and bradycardia with cardiac arrest have been observed a few minutes after the administration of sugammadex (see section 4.4).

Reappearance of neuromuscular blockade:

In clinical trials with patients treated with rocuronium or vecuronium, where sugammadex was administered using a dose established for the depth of neuromuscular blockade (N = 2,022), an incidence of 0.20% was observed for the reappearance of neuromuscular blockade, based on neuromuscular monitoring or clinical evidence (see section 4.4).

Information on healthy volunteers:

A randomized, double-blind study evaluated the incidence of suspected hypersensitivity reactions to the medication 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). The notifications of suspected hypersensitivity were established by an independent commission. The incidence of established 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 administration of placebo or sugammadex 4 mg/kg. There was only one case of established anaphylaxis after administration of the first dose of sugammadex 16 mg/kg (incidence of 0.7%). Upon repeating the sugammadex dose, there were no indications of an increase in the frequency or severity of hypersensitivity.

In a previous study of similar design, there were three cases of established anaphylaxis, all after administration of sugammadex 16 mg/kg (incidence of 2.0%).

In the combined Phase I database, common (≥ 1/100 to <1>

Additional information for special populations

Pulmonary complications:

In post-marketing data and in a specific clinical trial, in patients with a history of pulmonary complications, bronchospasm was reported as a possibly related adverse reaction. As with all patients with a history of pulmonary complications, the physician should be alert to the possible occurrence of bronchospasm.

Pediatric population

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

Patients with morbid obesity

In a specific clinical trial in patients with morbid obesity, the safety profile was generally similar to the profile in adult patients in combined Phase 1 to 3 trials (see Table 2).

Patients with severe systemic disease

In a trial in patients who were evaluated as Class 3 or 4 according to the American Society of Anesthesiologists (ASA) (i.e., patients with severe systemic disease or patients with severe systemic disease that constitutes a constant threat to life), the profile of adverse reactions in these Class ASA 3 and 4 patients was generally similar to that of adult patients in combined Phase 1 to 3 trials (see Table 2). See section 5.1.

Overdose

During clinical trials, one case of accidental overdose with 40 mg/kg was reported without any significant adverse reaction. In human tolerance studies, sugammadex was administered in doses of up to 96 mg/kg. No dose-related adverse reactions or serious adverse reactions were reported.

Sugammadex can be eliminated by hemodialysis with a high-flow filter, but not with a low-flow filter. Clinical trials indicate that plasma sugammadex concentrations are reduced by up to 70% after a 3- to 6-hour dialysis session.

List of excipients

Hydrochloric acid 3.7% (for pH adjustment) and/or sodium hydroxide (for pH adjustment)

Water for injectable preparations.

Shelf life

3 years

After first opening and dilution, chemical and physical stability has been demonstrated for 48 hours between 2°C and 25°C. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should generally not exceed 24 hours between 2°C and 8°C, unless the dilution has been performed in controlled and validated aseptic conditions.

Special precautions for storage

Store below 30°C.

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Special precautions for disposal and other handling

Bridion can be injected using the same line as for an already initiated 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%), Ringer's lactate solution, Ringer's solution, and glucose 50 mg/ml (5%) in sodium chloride 9 mg/ml (0.9%).

The infusion line should be adequately flushed (e.g., with a 0.9% sodium chloride solution) between administration of Bridion and other medications.

Use in the pediatric population

For pediatric patients, Bridion can be diluted using sodium chloride 9 mg/ml (0.9%) to a concentration of 10 mg/ml (see section 6.3).