Chemical formula: C₇₂H₁₀₄Na₈O₄₈S₈ Molecular mass: 2,002.12 g/mol PubChem compound: 6918585
Sugammadex interacts in the following cases:
Sugammadex is not metabolised nor excreted by the liver; therefore dedicated studies in patients with hepatic impairment have not been conducted. Patients with severe hepatic impairment should be treated with great caution.
The interaction between 4 mg/kg sugammadex and a progestogen was predicted to lead to a decrease in progestogen exposure (34% of AUC) similar to the decrease seen when a daily dose of an oral contraceptive is taken 12 hours too late, which might lead to a reduction in effectiveness. For oestrogens, the effect is expected to be lower. Therefore the administration of a bolus dose of sugammadex is considered to be equivalent to one missed daily dose of oral contraceptive steroids (either combined or progestogen only). If sugammadex is administered at the same day as an oral contraceptive is taken reference is made to missed dose advice in the package leaflet of the oral contraceptive. In the case of non-oral hormonal contraceptives, the patient must use an additional non hormonal contraceptive method for the next 7 days and refer to the advice in the package leaflet of the product.
The use of fusidic acid in the pre-operative phase may give some delay in the recovery of the T4/T1 ratio to 0.9. No recurrence of neuromuscular blockade is expected in the post-operative phase, since the infusion rate of fusidic acid is over a period of several hours and the blood levels are cumulative over 2-3 days.
For toremifene, which has a relatively high binding affinity for sugammadex and for which relatively high plasma concentrations might be present, some displacement of vecuronium or rocuronium from the complex with sugammadex could occur. Clinicians should be aware that the recovery of the T4/T1 ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of the operation.
In in vitro experiments a pharmacodynamic interaction (aPTT and PT prolongation) was noted with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran. In patients receiving routine post-operative prophylactic anticoagulation this pharmacodynamic interaction is not clinically relevant. Caution should be exercised when considering the use of sugammadex in patients receiving therapeutic anticoagulation for a pre-existing or comorbid condition.
An increased risk of bleeding cannot be excluded in patients:
If there is a medical need to give sugammadex to these patients the anaesthesiologist needs to decide if the benefits outweigh the possible risk of bleeding complications taking into consideration the patients history of bleeding episodes and type of surgery scheduled. If sugammadex is administered to these patients monitoring of haemostasis and coagulation parameters is recommended.
In post-marketing data and in one dedicated clinical trial in patients with a history of pulmonary complications, bronchospasm was reported as a possibly related adverse event. As with all patients with a history of pulmonary complications the physician should be aware of the possible occurrence of bronchospasm.
For sugammadex no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Caution should be exercised when administering sugammadex to pregnant women.
It is unknown whether sugammadex is excreted in human breast milk. Animal studies have shown excretion of sugammadex in breast milk. Oral absorption of cyclodextrins in general is low and no effect on the suckling child is anticipated following a single dose to the breast-feeding woman. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sugammadex therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
The effects with sugammadex on human fertility have not been investigated. Animal studies to evaluate fertility do not reveal harmful effects.
Sugammadex has no known influence on the ability to drive and use machines.
Sugammadex is administered concomitantly with neuromuscular blocking agents and anaesthetics in surgical patients. The causality of adverse events is therefore difficult to assess. The most commonly reported adverse reactions in surgical patients were cough, airway complication of anaesthesia, anaesthetic complications, procedural hypotension and procedural complication (Common (≥1/100 to <1/10)).
The safety of sugammadex has been evaluated in 3,519 unique subjects across a pooled phase I-III safety database. The following adverse reactions were reported in placebo controlled trials where subjects received anaesthesia and/or neuromuscular blocking agents (1,078 subject exposures to sugammadex versus 544 to placebo): [Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000)].
| System organ class | Frequencies | Adverse reactions (Preferred terms) |
|---|---|---|
| Immune system disorders | Uncommon | Drug hypersensitivity reactions |
| Respiratory, thoracic and mediastinal disorders | Common | Cough |
| Injury, poisoning and procedural complications | Common | Airway complication of anaesthesia Anaesthetic complication Procedural hypotension Procedural complication |
Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers. In clinical trials of surgical patients these reactions were reported uncommonly and for post-marketing reports the frequency is unknown.
These reactions varied from isolated skin reactions to serious systemic reactions (i.e. anaphylaxis, anaphylactic shock) and have occurred in patients with no prior exposure to sugammadex. Symptoms associated with these reactions can include: flushing, urticaria, erythematous rash, (severe) hypotension, tachycardia, swelling of tongue, swelling of pharynx, bronchospasm and pulmonary obstructive events. Severe hypersensitivity reactions can be fatal.
Airway complications of anaesthesia included bucking against the endotracheal tube, coughing, mild bucking, arousal reaction during surgery, coughing during the anaesthetic procedure or during surgery, or anaesthetic procedure-related spontaneous breath of patient.
Anaesthetic complications, indicative of the restoration of neuromuscular function, include movement of a limb or the body or coughing during the anaesthetic procedure or during surgery, grimacing, or suckling on the endotracheal tube.
Procedural complications included coughing, tachycardia, bradycardia, movement, and increase in heart rate.
In post-marketing, isolated cases of marked bradycardia and bradycardia with cardiac arrest have been observed within minutes after administration of sugammadex.
In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labelled for the depth of neuromuscular blockade (N=2,022), an incidence of 0.20% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence.
A randomised, double-blind study examined the incidence of drug hypersensitivity reactions in healthy volunteers given up to 3 doses of placebo (N=76), sugammadex 4 mg/kg (N=151) or sugammadex 16 mg/kg (N=148). Reports of suspected hypersensitivity were adjudicated by a blinded committee. The incidence of adjudicated hypersensitivity was 1.3%, 6.6% and 9.5% in the placebo, sugammadex 4 mg/kg and sugammadex 16 mg/kg groups, respectively. There were no reports of anaphylaxis after placebo or sugammadex 4 mg/kg. There was a single case of adjudicated anaphylaxis after the first dose of sugammadex 16 mg/kg (incidence 0.7%). There was no evidence of increased frequency or severity of hypersensitivity with repeat dosing of sugammadex.
In a previous study of similar design, there were three adjudicated cases of anaphylaxis, all after sugammadex 16 mg/kg (incidence 2.0%).
In the Pooled Phase 1 database, AEs considered common (≥1/100 to <1/10) or very common (≥1/10) and more frequent among subjects treated with sugammadex than in the placebo group, 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%).
In post-marketing data and in one dedicated clinical trial in patients with a history of pulmonary complications, bronchospasm was reported as a possibly related adverse event. As with all patients with a history of pulmonary complications the physician should be aware of the possible occurrence of bronchospasm.
In studies ofpaediatric patients 2 to 17 years of age, the safety profile of sugammadex (up to 4 mg/kg) was generally similar to the profile observed in adults.
In one dedicated clinical trial in morbidly obese patients, the adverse reaction profile was generally similar to the profile in adult patients in pooled Phase 1 to 3 studies.
In a trial in patients who were assessed as American Society of Anesthesiologists (ASA) Class 3 or 4 (patients with severe systemic disease or patients with severe systemic disease that is a constant threat to life), the adverse reaction profile in these ASA Class 3 and 4 patients was generally similar to that of adult patients in pooled Phase 1 to 3 studies.
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