Bridion 100 mg/ml solution for injection
Spain
Table of Contents
Package leaflet: Information for the user
Introduction
Package leaflet: information for the user
Bridion 100mg/ml solution for injection
sugammadex
Read the entire leaflet carefully before you are given this medicine, because it contains important information for you.
- Keep this leaflet as you may need to read it again.
- If you have any questions, ask your anaesthesiologist (anaesthetist) or your doctor.
- If you get any side effects, talk to your anaesthetist or another doctor, even if they are side effects not listed in this leaflet. See section 4.
Contents of the leaflet
- What Bridion is and what it is used for
- What you need to know before being given Bridion
- How Bridion is given
- Possible side effects
- How to store Bridion
- Contents of the pack and other information
1. What Bridion is and what it is used for
What Bridion is
Bridion contains the active substance sugammadex. Bridion is considered a Selective Relaxant Binding Agent because it works only with specific muscle relaxants, rocuronium bromide or vecuronium bromide.
What Bridion is used for
When you undergo surgery, your muscles must be completely relaxed, which makes it easier for the surgeon to perform the procedure. For this reason, during general anaesthesia you will be given medicines to relax your muscles. These are called neuromuscular blocking agents, such as rocuronium bromide and vecuronium bromide. Since these medicines also block the muscles used for breathing, you will need assistance with breathing (mechanical ventilation) during and after your surgery until you are able to breathe on your own again.
Bridion is used to speed up the recovery of muscle function after surgery so that you can breathe on your own again sooner. It works by binding to rocuronium bromide or vecuronium bromide in your body. It can be used in adults whenever rocuronium bromide or vecuronium bromide is used.
It can also be used in newborns, infants, children, and adolescents (from birth up to 17 years of age) when rocuronium bromide is used.
2. What you need to know before receiving Bridion
Do not receive Bridion
- 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
Talk to your anaesthetist before receiving Bridion
- if you have kidney disease or have had it in the past. This is important because Bridion is eliminated from your body through the kidneys.
- if you have liver disease or have had it previously.
- if you have fluid retention (oedema).
- if you have a condition that increases the risk of bleeding (blood clotting disorders) or if you are taking anticoagulant medication.
Other medicines and Bridion
→ Inform your anaesthetist if you are taking, have recently taken, or might need to take any other medicines.
Bridion may affect other medicines or may be affected by them.
Some medicines reduce the effect of Bridion
→ It is especially important that you inform 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-h) — less effective because it reduces the amount of progestogen hormone available. The amount of progestogen lost due to the use of Bridion is approximately the same as when you miss one contraceptive pill.
→ If you are taking the Pill on the same day that Bridion is administered, follow the missed tablet instructions provided in the pill leaflet.
→ If you are using other hormonal contraceptives (e.g. vaginal ring, implant, or IUD-h), you should use an additional non-hormonal contraceptive method (such as a condom) for the next 7 days and follow the recommendations in the product leaflet.
Effects on blood tests
In general, Bridion does not have any known effects on laboratory tests. However, it may affect the results of a blood test measuring levels of the hormone progesterone. Consult your doctor if progesterone levels need to be tested on the same day you receive Bridion.
Pregnancy and breastfeeding
→ Inform your anaesthetist if you are pregnant or may be pregnant, or if you are breastfeeding.
You may still be given Bridion, but this should be discussed beforehand.
It is not known whether sugammadex passes into breast milk. Your anaesthetist will help you decide whether to interrupt breastfeeding or to avoid treatment with sugammadex, taking into account the benefits of breastfeeding for the baby and the benefits of Bridion for the mother.
Driving and using machines
Bridion has no known influence on the ability to drive or use machines.
Bridion contains sodium
This medicine contains up to 9.7 mg of sodium (the main component of table/cooking salt) per ml. This corresponds to 0.5% of the maximum daily recommended intake of sodium for an adult.
3. How Bridion is administered
Bridion will be administered to you by your anaesthetist, or under the supervision of your anaesthetist.
Dosage
Your anaesthetist will calculate the dose of Bridion you need based on:
- your body weight
- the amount of muscle relaxant 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 reversal of muscle relaxation is required.
How Bridion is administered
Bridion will be administered by your anaesthetist. It is given as a single intravenous injection.
If you are given more Bridion than recommended
As your anaesthetist will be carefully monitoring your condition, it is unlikely that you will receive too much Bridion. However, even if this happens, it is unlikely to cause any problems.
If you have any further questions about the use of this medicine, ask your anaesthetist or another doctor.
4. Possible adverse effects
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If these adverse effects occur while you are under the effects of anesthesia, your anesthetist will detect and treat them.
Frequent (may affect up to 1 in 10 people)
- Cough
- Respiratory tract difficulties which may include coughing or movements as if awake or taking a breath
- Light anesthesia – you may begin to wake up, so you will need more anesthetic. This may cause you to move or cough at the end of the operation
- Complications during the procedure, such as changes in heart rate, coughing, or movement
- Decrease in blood pressure due to the surgical intervention
Uncommon (may affect up to 1 in 100 people)
-
Difficulty breathing due to muscle spasms in the airways (bronchospasm), occurring in patients with a history of lung problems
-
Allergic reactions (hypersensitivity to medicines) – such as rash, redness of the skin, swelling of the tongue and/or pharynx, difficulty breathing, changes in blood pressure or heart rhythm, which sometimes result in a severe drop in blood pressure. Allergy-type reactions or severe allergic reactions may be life-threatening
Allergic reactions were reported more frequently in healthy conscious volunteers
- Recurrence of muscle relaxation after surgery
Frequency not known
- When Bridion is administered, a significant slowing of the heart rate may occur, which could even lead to cardiac arrest
Reporting of adverse effects
If you experience any type of adverse effect, consult your anesthetist or another doctor, even if these are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Bridion
Storage must be handled 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 the month indicated.
Store below 30 °C. Do not freeze. Keep the vial in the outer packaging to protect it from light.
After opening and dilution, store at 2–8 °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 and containers you no longer need. This will help protect the environment.
6. Contents of the pack and other 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 components are water for injections, hydrochloric acid 3.7% and/or sodium hydroxide.
Appearance of the product and contents of the pack
Bridion is a clear, colourless to slightly yellowish injectable solution.
It is available in two pack sizes: 10 vials of 2 ml or 10 vials of 5 ml of injectable solution.
Only some pack sizes may be marketed.
Marketing Authorization Holder Merck Sharp & Dohme B.V. Waarderweg 39 2031 BN Haarlem The Netherlands | Manufacturer Responsible N.V. Organon Kloosterstraat 6 5349 AB Oss The Netherlands Merck Sharp & Dohme B.V. Waarderweg 39 2031 BN Haarlem The Netherlands |
You can request further information about this medicinal product by contacting the local representative of the marketing authorization holder:
Belgium/Belgium/Belgium MSD Belgium Tel/Tel: +32(0)27766211 | Lithuania UAB Merck Sharp & Dohme Tel. +370 5 2780 247 |
| Luxembourg/Luxembourg MSD Belgium Tel/Tel: +32(0)27766211 |
Czech Republic Merck Sharp & Dohme s.r.o. Tel.: +420 277 050 000 | Hungary MSD Pharma Hungary Kft. Tel.: +36 1 888 5300 |
Denmark MSD Danmark ApS Tlf.: +45 4482 4000 | Malta Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558) |
Germany MSD Sharp & Dohme GmbH Tel.: +49 (0) 89 20 300 4500 | Netherlands Merck Sharp & Dohme B.V. Tel: 0800 9999000 (+31 23 5153153) |
Estonia Merck Sharp & Dohme OÜ Tel: +372 614 4200 | Norway MSD (Norge) AS Tlf: +47 32 20 73 00 |
Greece MSD Α.Φ.Ε.Ε. Tel: +30 210 98 97 300 | Austria Merck Sharp & Dohme Ges.m.b.H. Tel: +43 (0) 1 26 044 |
Spain Merck Sharp & Dohme de España, S.A. Tel: +34 91 321 06 00 | Poland MSD Polska Sp. z o.o. Tel.: +48 22 549 51 00 |
France MSD France Tel: +33 (0)1 80 46 40 40 | Portugal Merck Sharp & Dohme, Lda Tel.: +351 21 4465700 |
Croatia Merck Sharp & Dohme d.o.o. Tel: +385 1 6611 333 | Romania Merck Sharp & Dohme Romania S.R.L. Tel.: +40 21 529 29 00 |
Ireland Merck Sharp & Dohme Ireland (Human Health) Limited Tel: +353 (0)1 2998700 | Slovenia Merck Sharp & Dohme, inovativna zdravila d.o.o. Tel: +386 1 520 4201 |
Iceland Vistor ehf. Tel: +354 535 7000 | Slovakia Merck Sharp & Dohme, s. r. o. Tel.: +421 2 58282010 |
Italy MSD Italia S.r.l. Tel: 800 23 99 89 (+39 06 361911) | Finland/Sweden MSD Finland Oy Tel: +358 (0)9 804 650 |
Cyprus Merck Sharp & Dohme Cyprus Limited Tel: 800 00 673 (+357 22866700) | Sweden Merck Sharp & Dohme (Sweden) AB Tel: +46 77 5700488 |
Latvia SIA Merck Sharp & Dohme Latvija Tel.: +371 67025300 |
Date of last review of this leaflet: <{MM/YYYY}><{month YYYY}>.
Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.
This information is intended for healthcare professionals only:
For detailed information, refer to the Summary of Product Characteristics (SmPC) for BRIDION.
Therapeutic indications and dosage
Reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults.
For the paediatric population: sugammadex is recommended only in paediatric patients from birth to 17 years of age for routine reversal of rocuronium-induced blockade.
Sugammadex must only be administered by, or under the supervision of, an anaesthesiologist.
An appropriate neuromuscular monitoring technique is recommended to monitor recovery from neuromuscular blockade (see SmPC, section 4.4).
Adults
Routine reversal:
A dose of 4 mg/kg sugammadex is recommended when recovery has reached at least 1–2 post-tetanic counts (PTC) following rocuronium- or vecuronium-induced blockade. The median time to recover a T4/T1 ratio of 0.9 is approximately 3 minutes (see SmPC, section 5.1).
A dose of 2 mg/kg sugammadex is recommended when spontaneous recovery has occurred to at least the reappearance of T2 following rocuronium- or vecuronium-induced blockade. The median time to recover a T4/T1 ratio of 0.9 is approximately 2 minutes (see SmPC, section 5.1).
When the recommended doses for routine reversal are used, the median time to recover a T4/T1 ratio of 0.9 for rocuronium will be slightly faster compared to neuromuscular blockade induced by vecuronium (see SmPC, section 5.1).
Immediate reversal of rocuronium-induced neuromuscular blockade:
If there is a clinical need for immediate reversal after administration of rocuronium, a dose of 16 mg/kg sugammadex is recommended. When 16 mg/kg sugammadex is administered 3 minutes after a bolus dose of 1.2 mg/kg rocuronium bromide, recovery to a T4/T1 ratio of 0.9 can be expected in a median time of approximately 1.5 minutes (see SmPC, section 5.1).
There are no available data to recommend the use of sugammadex for immediate reversal following vecuronium-induced blockade.
Repeat administration of sugammadex:
In the rare event that postoperative neuromuscular blockade recurs (see SmPC, section 4.4) after an initial dose of 2 mg/kg or 4 mg/kg sugammadex, administration of a further dose of 4 mg/kg sugammadex is recommended. After the second dose of sugammadex, the patient should be closely monitored to confirm sustained recovery of neuromuscular function.
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 those with morbid obesity (body mass index ≥ 40 kg/m²), the sugammadex dose should be based on actual body weight. The same dosing recommendations as those for adults should be followed.
Paediatric population (from birth to 17 years of age)
The Bridion 100 mg/ml injectable solution 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 at least 1–2 PTCs.
A dose of 2 mg/kg is recommended for reversal of rocuronium-induced blockade when T2 reappears (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 is customary in post-anaesthesia practice following neuromuscular blockade, patients should be monitored in the immediate postoperative period for unexpected effects such as recurrence of neuromuscular blockade.
Monitoring of respiratory function during recovery:
Mechanical ventilation is mandatory until adequate spontaneous respiration has returned following reversal of neuromuscular blockade. Even if neuromuscular blockade has been fully reversed, other medications used in the peri- and postoperative periods may depress respiratory function, so mechanical ventilation may still be required.
If neuromuscular blockade recurs after extubation, adequate ventilation should be provided.
Recurrence of neuromuscular blockade:
In clinical trials in patients treated with rocuronium or vecuronium, where sugammadex was administered at a dose appropriate to the depth of neuromuscular blockade, an incidence of 0.20% for recurrence of neuromuscular blockade was observed, based on neuromuscular monitoring or clinical evidence. Using doses lower than those recommended may increase the risk of recurrence of neuromuscular blockade after initial reversal and is therefore not recommended (see SmPC, sections 4.2 and 4.8).
Effect on haemostasis:
In a study in healthy volunteers, doses of 4 mg/kg and 16 mg/kg sugammadex resulted in mean maximum prolongations of activated partial thromboplastin time (aPTT) by 17% and 22%, respectively, and international normalized ratio of prothrombin time [PT(INR)] by 11% and 22%, respectively. These mean prolongations in aPTT and PT(INR) were of short duration (≤ 30 minutes). Based on the clinical database (N=3,519), and a specific study in 1,184 patients undergoing hip fracture surgery/joint replacement surgery, 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.
Pharmacodynamic interactions (prolongation of activated partial thromboplastin time [aPTT] and prothrombin time [PT]) have been observed in vitro with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran. In patients receiving standard postoperative prophylactic anticoagulation, this pharmacodynamic interaction is not clinically relevant. Caution should be exercised when considering the use of sugammadex in patients receiving anticoagulant therapy for a pre-existing or concomitant 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 factor 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 anaesthesiologist 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. Monitoring of haemostasis and coagulation parameters is recommended if sugammadex is administered to these patients.
Recommended waiting times before re-administering neuromuscular blocking agents after reversal with sugammadex:
Table 1: Re-administration of rocuronium or vecuronium after routine reversal (up to 4 mg/kg sugammadex):
Minimum waiting time | NMB and dose to be administered |
5 minutes | 1.2 mg/kg rocuronium |
4 hours | 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium |
After re-administration of 1.2 mg/kg rocuronium within 30 minutes following sugammadex administration, the onset of neuromuscular blockade may be delayed by approximately 4 minutes, and the duration of neuromuscular blockade may be reduced by approximately 15 minutes.
Based on the pharmacokinetic (PK) model, the recommended waiting time in patients with mild or moderate renal impairment for re-administration 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 blockade should be 1.2 mg/kg.
Re-administration of rocuronium or vecuronio 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 neuromuscular blockade needs to be administered before the recommended waiting time, a non-steroidal neuromuscular blocker should be used. The onset of a depolarizing neuromuscular blocker may be slower than expected, as a substantial fraction of postsynaptic 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 requiring dialysis (see FT, section 5.1).
Superficial anesthesia:
In clinical trials, when neuromuscular blockade was intentionally reversed during anesthesia, signs of superficial anesthesia (movements, coughing, facial spasms, and endotracheal tube biting) were occasionally observed.
If neuromuscular blockade is reversed while anesthesia continues, additional doses of anesthetic and/or opioid should be administered as clinically indicated.
Profound bradycardia:
In rare cases, profound bradycardia has been observed a few minutes after administration of sugammadex for reversal of neuromuscular blockade. In some instances, bradycardia may lead to cardiac arrest (see FT, section 4.8). Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. If clinically significant bradycardia occurs, treatment with anticholinergics such as atropine should be administered.
Hepatic impairment:
Sugammadex is not metabolized or eliminated by the liver; therefore, no specific studies have been conducted in patients with hepatic impairment. Patients with severe hepatic impairment should be treated with great caution. In cases where hepatic impairment is accompanied by coagulopathy, refer to the information on the effect on hemostasis.
Use in Intensive Care Units (ICU):
Sugammadex has not been investigated in patients who have received rocuronium or vecuronium in the ICU.
Reversal of neuromuscular blockade caused by drugs other than rocuronium or vecuronium:
Sugammadex treatment should not be used to reverse blockade induced by non-steroidal neuromuscular blockers such as succinylcholine or benzylisoquinolinium derivatives.
Sugammadex treatment should not be used for reversal of neuromuscular blockade induced by steroidal neuromuscular blockers other than rocuronium or vecuronium, as efficacy and safety data are not available in these cases. Limited data are available regarding reversal of pancuronium-induced blockade, but sugammadex is not recommended in this situation.
Delayed recovery:
Conditions associated with prolonged circulation time, such as cardiac disease, advanced age (see FT, section 4.2 regarding recovery time in elderly patients), or edematous states (e.g., severe hepatic impairment), may be associated with prolonged recovery times.
Hypersensitivity reactions:
Physicians should be prepared for the possibility of hypersensitivity reactions (including anaphylactic reactions) and should take necessary precautions (see FT, 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 drugs, non-clinical experiments, clinical trials, and simulations using a model that accounts for the pharmacodynamic effect of neuromuscular blockers and the pharmacokinetic interaction between neuromuscular blockers and sugammadex. Based on these data, clinically significant pharmacodynamic interactions with other drugs are not expected, except for the following:
Toremifene and fusidic acid: the possibility of displacement interactions cannot be excluded (no clinically relevant encapsulation interactions are expected).
Hormonal contraceptives: the possibility of a clinically relevant encapsulation interaction cannot be excluded (no displacement interactions are expected).
Interactions potentially affecting the efficacy of sugammadex (displacement interactions):
Theoretically, administration of certain drugs after sugammadex treatment may displace rocuronium or vecuronium from the sugammadex complex, resulting in recurrence of neuromuscular blockade. In such cases, mechanical ventilation should be provided to the patient. Administration of the displacing drug should be discontinued if given by infusion. In situations where potential displacement interactions may be anticipated following parenteral administration of another drug within 7.5 hours after sugammadex administration, patients should be carefully monitored for signs of recurrence of neuromuscular blockade (for approximately 15 minutes).
Toremifene:
With concomitant administration of toremifene, which has relatively high binding affinity for sugammadex and may be present at relatively high plasma concentrations, some displacement of rocuronium or vecuronium from the sugammadex complex 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 day of surgery.
Intravenous administration of fusidic acid:
Preoperative use of fusidic acid may cause some delay in recovery of the T4/T1 ratio to 0.9. Recurrence of neuromuscular blockade is not expected in the postoperative phase, as fusidic acid infusion lasts several hours and blood levels accumulate over 2–3 days. See FT section 4.2 for re-administration of sugammadex.
Interactions potentially affecting the efficacy of other medicinal products (encapsulation interactions):
Administration of sugammadex may reduce plasma concentrations (free) of certain drugs, potentially decreasing their efficacy. If this occurs, the physician should consider re-administering the same drug, administering a therapeutically equivalent drug (preferably from a different chemical class), and/or applying necessary non-pharmacological interventions.
Hormonal contraceptives:
The interaction between sugammadex 4 mg/kg and progestogen is expected to reduce progestogen exposure (34% of AUC), similar to the reduction observed when a daily dose of oral contraceptive is taken 12 hours late, which may lead to reduced effectiveness. For estrogens, the effect is expected to be less pronounced. Therefore, administration of a bolus dose of sugammadex is considered equivalent to missing a daily dose of an oral steroidal contraceptive (either combined or progestogen-only). If sugammadex is administered on the same day as an oral contraceptive, refer to the recommendations for missed dose in the oral contraceptive’s product leaflet. For non-oral hormonal contraceptives, the patient should use a non-hormonal contraceptive method for the next 7 days and follow the product leaflet recommendations.
Interactions due to prolonged effect of rocuronium or vecuronium:
If drugs that potentiate neuromuscular blockade are used in the postoperative period, special attention should be paid to the possibility of recurrence of neuromuscular blockade. See the product leaflets of rocuronium or vecuronium for a list of specific drugs that potentiate neuromuscular blockade. In case of recurrence of neuromuscular blockade, the patient may require mechanical ventilation and repeat dosing of sugammadex (see FT, section 4.2).
Fertility, pregnancy, and lactation
Pregnancy
There are no clinical data on exposure to sugammadex in pregnant women.
Animal studies do not suggest direct or indirect harmful effects on pregnancy, embryofetal development, parturition, or postnatal development.
Sugammadex should be used with caution in pregnant women.
Lactation
It is unknown whether sugammadex is excreted in human breast milk. Animal studies have shown that sugammadex is excreted in milk. Oral absorption of cyclodextrins is generally low, and no effect on the breastfed infant is expected after a single dose administered to the mother during lactation.
A decision must be made whether to discontinue breastfeeding or discontinue therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Fertility
The effects of sugammadex on human fertility have not been studied. Animal studies to evaluate fertility showed no adverse effects.
Adverse reactions
Summary of safety profile
Bridion was administered concomitantly with neuromuscular blockers and anesthetics in surgical patients. Therefore, causality of adverse effects is difficult to assess.
The most frequently reported adverse reactions in surgical patients were cough, respiratory complications due to anesthesia, anesthesia complications, hypotension due to therapeutic procedure, and surgical complications (Frequent (≥ 1/100 to < 1/10)).
Table 2: Table of adverse reactions
The safety of sugammadex has been evaluated in 3,519 individual patients through a combined phase I–III safety database. The following adverse reactions were reported in placebo-controlled trials in which patients received anesthesia and/or neuromuscular blockers (1,078 patients exposed to sugammadex vs. 544 exposed to placebo):
[Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000)]
System organ classification | Frequencies | Adverse reactions (Preferred terms) |
Immune system disorders | Uncommon | Hypersensitivity reactions (see SmPC, section 4.4) |
Respiratory, thoracic and mediastinal disorders | Common | Cough |
Injury, poisoning and procedural complications | Common | Respiratory complications due to anaesthesia Anaesthetic complications (see SmPC, section 4.4) Hypotension due to therapeutic procedure Surgical complication |
Description of selected adverse reactions
Hypersensitivity reactions:
Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers (for information on volunteers, see below, Healthy volunteer information). In clinical trials of surgical patients, these reactions were reported infrequently, and in post-marketing reports, the frequency is unknown.
These reactions ranged from isolated skin reactions to serious 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, hypotension (severe), tachycardia, tongue swelling, pharyngeal swelling, bronchospasm, and obstructive pulmonary events. Severe hypersensitivity reactions may be fatal.
In post-marketing reports, hypersensitivity has been observed with both sugammadex and the sugammadex-rocuronium complex.
Respiratory complications related to anaesthesia:
Respiratory complications related to anaesthesia included spasms associated with the end of anaesthesia or extubation against the endotracheal tube, coughing, mild spasms related to the end of anaesthesia or extubation, awakening reaction during surgery, coughing during the anaesthetic procedure or during surgery, or patient spontaneous breathing related to the anaesthetic procedure.
Anaesthesia complications:
Anaesthesia complications, indicating recovery of neuromuscular function, include limb or body movement or coughing during administration of anaesthesia or during surgery, facial spasms, or suctioning at the endotracheal tube. See SmPC, section 4.4, superficial anaesthesia.
Procedure-related complications:
Procedure-related complications included coughing, movement, tachycardia, bradycardia, and increased heart rate.
Profound bradycardia:
After marketing authorisation, isolated cases of profound bradycardia and bradycardia with cardiac arrest have been observed a few minutes after administration of sugammadex (see SmPC, 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% for reappearance of neuromuscular blockade was observed, based on neuromuscular monitoring or clinical evidence (see SmPC, section 4.4).
Information on healthy volunteers:
A randomised, 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). Suspected hypersensitivity reactions were adjudicated by an independent committee. The incidence of confirmed 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. Only one confirmed case of anaphylaxis occurred after administration of the first dose of sugammadex 16 mg/kg (incidence of 0.7%). Upon repeat dosing with sugammadex, there was no indication of increased frequency or severity of hypersensitivity.
In a previous study with a similar design, there were three confirmed cases of anaphylaxis, all after administration of sugammadex 16 mg/kg (incidence of 2.0%).
In the pooled Phase I clinical trial database, adverse reactions that were common (≥ 1/100 to < 1/10), very common (≥ 1/10), and more frequent in patients treated with sugammadex than in the placebo group include dysgeusia (10.1%), headache (6.7%), nausea (5.6%), urticaria (1.7%), pruritus (1.7%), dizziness (1.6%), vomiting (1.2%), and abdominal pain (1.0%).
Additional information for special populations
Pulmonary complications:
In post-marketing data and in a specific clinical trial, bronchospasm was reported as an adverse reaction possibly related to treatment in patients with a history of pulmonary complications. As with all patients with a history of pulmonary complications, physicians should be vigilant for 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 morbid obesity
In a specific clinical trial in patients with morbid obesity, the safety profile was generally similar to that in adult patients in combined Phase 1 to 3 trials (see Table 2).
Patients with severe systemic disease
In a trial in patients classified as ASA Class 3 or 4 (i.e., patients with severe systemic disease or patients with severe systemic disease that is a constant threat to life), the adverse reaction profile in these ASA Class 3 and 4 patients was generally similar to that in adult patients in combined Phase 1 to 3 trials (see Table 2). See SmPC, section 5.1.
Overdose
During clinical trials, one case of accidental overdose with 40 mg/kg was reported, with no significant adverse reactions occurring. In human tolerance studies, sugammadex was administered at doses up to 96 mg/kg. No dose-related adverse reactions or serious adverse reactions were reported.
Sugammadex can be removed by haemodialysis using a high-flux filter, but not with a low-flux filter. Clinical trials indicate that plasma concentrations of sugammadex can be 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 injections.
Shelf life
3 years
After first opening and dilution, chemical and physical in-use stability has been demonstrated for 48 hours between 2 °C and 25 °C. From a microbiological standpoint, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should generally not exceed 24 hours between 2 °C and 8 °C, unless dilution has been carried out under validated aseptic 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 after dilution of the medicinal product, see SmPC, section 6.3.
Special precautions for disposal and other handling
Bridion may be administered via the same line as an ongoing 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 0.9% sodium chloride solution) between the administration of Bridion and other medications.
Use in the paediatric population
For paediatric patients, Bridion may be diluted using sodium chloride 9 mg/ml (0.9%) to a concentration of 10 mg/ml (see SmPC, section 6.3).