Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
As is normal post-anaesthetic practice following neuromuscular blockade, it is recommended to monitor the patient in the immediate post-operative period for untoward events including recurrence of neuromuscular blockade.


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.


Recurrence of neuromuscular blockade:
In clinical studies with subjects treated with rocuronium or vecuronium, where sugammadex was administered using a dose labelled for the depth of neuromuscular blockade, 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 section 4.2 and section 4.8).


Effect on haemostasis:
In a study in volunteers doses of 4 mg/kg and 16 mg/kg of sugammadex resulted in maximum mean prolongations of the activated partial thromboplastin time (aPTT) by 17 and 22% respectively and prothrombin time international normalised ratio [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=3,519) and on a specific study in 1184 patients undergoing hip fracture/major joint replacement surgery there was no clinically relevant effect of sugammadex 4 mg/kg alone or in combination with anticoagulants on the incidence of peri- or post-operative bleeding complications.


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 co- morbid condition.


An increased risk of bleeding cannot be excluded in patients:
•   with hereditary vitamin K dependent clotting factor deficiencies;
•   with pre-existing coagulopathies;
•   on coumarin derivates and at an INR above 3.5;
•     using anticoagulants who receive a dose of 16 mg/kg sugammadex.
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.


Waiting times for re-administration with 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                      NMBA 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


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


Based 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:
The use of sugammadex in patients with severe renal impairment is contraindicated and is not reccomended in patients requiring dialysis (see section 5.1).


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 section 4.8.) 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 not be treated with Sugammadex.
In case hepatic impairment is accompanied by coagulopathy see the information on the effect on haemostasis.


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 section 4.2 for the time to recovery in elderly), or oedematous state (e.g., severe hepatic impairment) may be associated with longer recovery times.


Drug hypersensitivity reactions:
Clinicians should be prepared for the possibility of drug hypersensitivity reactions (including anaphylactic reactions) and take the necessary precautions (see section 4.8).


Sodium:
This medicinal product contains up to 9.45 mg sodium per mL, equivalent to 0.47 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7 Effects on ability to drive and use machines
SUGAMEDIN has no known influence on the ability to drive and use machines.