Monitoring respiratory function during recovery:
Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored following reversal of neuromuscular blockade. Even if recovery from neuromuscular blockade is complete, other medicinal products used in the peri- and post-operative period could depress respiratory function and therefore ventilatory support might still be required.
Should neuromuscular blockade reoccur following extubation, adequate ventilation should be provided.
Effect on hemostasis:
In a study in volunteers, doses of 4mg/kg and 16mg/kg of sugammadex resulted in maximum mean prolongations of aPTT by 17 and 22% respectively and of PT (INR) by 11 and 22% respectively. These limited mean aPTT and PT (INR) prolongations were of short duration (≤ 30 minutes). Based on the clinical data-base (N=3519) there was no clinically relevant effect of sugammadex alone or in combination with anticoagulants on the incidence of peri- or post-operative bleeding complications.
In a specific study in 1184 surgical patients who were concomitantly treated with an anticoagulant, small and transient increases were observed in aPTT and PT (INR) associated with sugammadex 4 mg/kg, which did not translate into an increased bleeding risk with sugammadex compared with usual treatment.
In in vitro experiments additional aPTT and PT prolongation was noted for sugammadex in combination with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran. Considering the transient nature of the limited prolongation of a PTT and PT caused by sugammadex alone or on top of these anticoagulants, it is unlikely that sugammadex has an increased risk of bleeding. Since bleeding risk has not been studied systematically at higher doses than sugammadex 4 mg/kg, coagulation parameters should be carefully monitored according to routine clinical practice in patients with known coagulopathies and in patients using anticoagulants who receive a dose of 16 mg/kg sugammadex.
Recurrence of neuromuscular blockade:
In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labeled for the depth of neuromuscular blockade (N=2022), an incidence of 0.20% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence. The use of lower than recommended doses may lead to an increased risk of recurrence of neuromuscular blockade after initial reversal and is not recommended (see Dosage & Administration and Adverse Reactions).
Waiting times for re-administration with neuromuscular blocking agents after reversal with sugammadex:
Re-administration of rocuronium or vecuronium after routine reversal (up to 4 mg/kg sugammadex): (See Table 7).
Click on icon to see table/diagram/image
When rocuronium 1.2 mg/kg is administered within 30 minutes after reversal with Bridion, the onset of neuromuscular blockade may be delayed up to approximately 4 minutes and the duration of neuromuscular blockade may be shortened up to approximately 15 minutes.
Based on PK modeling the recommended waiting time in patients with mild or moderate renal impairment for re-use of 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium after routine reversal with sugammadex should be 24 hours. If a shorter waiting time is required, the rocuronium dose for a new neuromuscular blockade should be 1.2 mg/kg.
Re-administration of rocuronium or vecuronium after immediate reversal (16 mg/kg sugammadex): For the very rare cases where this might be required, a waiting time of 24 hours is suggested.
If neuromuscular blockade is required before the recommended waiting time has passed, a nonsteroidal neuromuscular blocking agent should be used. The onset of a depolarizing neuromuscular blocking agent might be slower than expected, because a substantial fraction of postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent.
Sugammadex is not recommended for use in patients with severe renal impairment, including those requiring dialysis (see Pharmacology: Pharmacodynamics under Actions).
Interactions due to the lasting effect of rocuronium or vecuronium:
When medicinal products which potentiate neuromuscular blockade are used in the post-operative period special attention should be paid to the possibility of recurrence of neuromuscular blockade. Please refer to the package leaflet of rocuronium or vecuronium for a list of the specific medicinal products which potentiate neuromuscular blockade. In case recurrence of neuromuscular blockade is observed, the patient may require mechanical ventilation and re-administration of sugammadex (see Dosage & Administration).
Capturing interactions: Due to the administration of sugammadex, certain medicinal products could become less effective due to a lowering of the (free) plasma concentrations (see Interactions potentially affecting the efficacy of other medicinal products (see also Precautions): Hormonal contraceptives under Interactions).
If such a situation is observed, the clinician is advised to consider the re-administration of the medicinal product, the administration of a therapeutically equivalent medicinal product (preferably from a different chemical class) and/or non-pharmacological interventions as appropriate.
Displacement interactions: Due to the administration of certain medicinal products after sugammadex, theoretically rocuronium or vecuronium could be displaced from sugammadex. Displacement interactions are at present only expected for a few drug substances (toremifene and fusidic acid, see Interactions). As a result recurrence of neuromuscular blockade might be observed. In this situation the patient must be ventilated. Administration of the medicinal product which caused displacement should be stopped in case of an infusion. In situations when potential displacement interactions can be anticipated, patients should be carefully monitored for signs of recurrence of neuromuscular blockade (approximately up to 15 minutes) after parenteral administration of another medicinal product occurring within a period of 7.5 hours after sugammadex administration.
When neuromuscular blockade was reversed intentionally in the middle of anesthesia in clinical trials, signs of light anesthesia were noted occasionally (movement, coughing, grimacing and suckling of the tracheal tube).
If neuromuscular blockade is reversed, while anesthesia is continued, additional doses of anesthetic and/or opioid should be given as clinically indicated.
In rare instances, marked bradycardia has been observed within minutes after the administration of sugammadex for reversal of neuromuscular blockade. Isolated cases of bradycardia with cardiac arrest have been reported. (See Adverse Reactions.) Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. Treatment with anti-cholinergic agents such as atropine should be administered if clinically significant bradycardia is observed.
Sugammadex is not metabolized 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. In case hepatic impairment is accompanied by coagulopathy see the information on the effect on hemostasis.
Use in Intensive Care Unit (ICU):
Sugammadex has not been investigated in patients receiving rocuronium or vecuronium in the ICU setting.
Use for reversal of neuromuscular blocking agents other than rocuronium or vecuronium:
Sugammadex should not be used to reverse block induced by nonsteroidal neuromuscular blocking agents such as succinylcholine or benzylisoquinolinium compounds.
Sugammadex should not be used for reversal of neuromuscular blockade induced by steroidal neuromuscular blocking agents other than rocuronium or vecuronium, since there are no efficacy and safety data for these situations. Limited data are available for reversal of pancuronium induced blockade, but it is advised not to use sugammadex in this situation.
Conditions associated with prolonged circulation time such as cardiovascular disease, old age (see Dosage & Administration for the time to recovery in elderly), or oedematous state (e.g., severe hepatic impairment) may be associated with longer recovery times.
Clinicians should be prepared for the possibility of drug hypersensitivity reactions (including anaphylactic reactions) and take the necessary precautions (see Adverse Reactions).
Patients on a controlled sodium diet:
Each ml solution contains 9.7 mg sodium. A dose of 23 mg sodium is considered essentially 'sodium-free'. If more than 2.4 ml solution needs to be administered, this should be taken into consideration by patients on a controlled sodium diet.
Effects on ability to drive and use machines:
Bridion has no known influence on the ability to drive and use machines.