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Should neuromuscular blockade reoccur following extubation, adequate ventilation should be provided.
Effect on haemostasis: In vitro experiments, a prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) has been observed with sugammadex in combination with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran.
In a study in volunteers, sugammadex doses of 4 mg/kg and 16 mg/kg resulted in a maximum mean prolongation of aPTT of 17% with 4 mg/kg and 22% with 16 mg/kg and a maximum mean prolongation of PT (international normalized ratio, INR) of 11% with 4 mg/kg and 22% with 16 mg/kg. These limited mean prolongations of aPTT and PT (INR) were of short duration (<=30 minutes). Based on clinical data (n=1738), there was no clinically significant effect of sugammadex alone or in combination with anticoagulants on the incidence of perioperative or postoperative bleeding complications.
Considering the transient nature of the limited prolongation of aPPT and PT caused by sugammadex alone or in combination with these anticoagulants, it is unlikely that sugammadex would cause an increased risk of bleeding. Since there is no information on the use of sugammadex in patients with known coagulation disorders, careful monitoring of coagulation parameters is recommended according to routine clinical rule.
Recurrence of neuromuscular blockade: Recurrence of neuromuscular blockade has been reported in clinical trials mainly at suboptimal doses (dose-finding studies). To prevent recurrence of neuromuscular block, the usual recommended reversal doses should be administered promptly (see Precautions).
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/imageBased on PK modelling 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.
Renal impairment: 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. Refer to the monograph 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).
Interactions: Interactions due to occupancy: 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: 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. 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.
To date, substitution interactions have been reported with a few drugs (see Interactions potentially affecting the efficacy of sugammadex: Toremifene and Intravenous administration of fusidic acid under Interactions).
Light anaesthesia: When neuromuscular blockade was reversed intentionally in the middle of anaesthesia in clinical trials, signs of light anaesthesia were noted occasionally (movement, coughing, grimacing and suckling of the tracheal tube).
If neuromuscular blockade is reversed, while anaesthesia is continued, additional doses of anaesthetic and/or opioid should be given as clinically indicated.
Marked bradycardia: In rare instances, marked bradycardia has been observed within minutes after the administration of sugammadex for reversal of neuromuscular blockade. Bradycardia may occasionally lead to cardiac arrest. (See Adverse Reactions). Patients should be closely monitored for haemodynamic 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.
Hepatic impairment: 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. In case hepatic impairment is accompanied by coagulopathy see the information on the Effect on haemostasis as previously mentioned.
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.
Delayed recovery: 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 may be associated with longer recovery times.
Drug hypersensitivity reactions: Clinicians should be prepared for the possibility of drug hypersensitivity reactions and take the necessary precautions (see Adverse Reactions).
Patients on controlled sodium diets: Each mL of solution contains 9.4 mg sodium. Each dose containing 23 mg sodium is said to be "sodium free".
If more than 2.5 mL of solution is required, this should be considered in patients on a controlled salt diet.
Effects on Ability to Drive and Use Machines: There is no evidence of the effect of the drug on the ability to drive and use machines.
