Sugammadex Equity 100 Mg Solution

SUGAMMADEX EQUITY is indicated for the routine reversal of neuromuscular blockade induced by rocuronium or vecuronium. SUGAMMADEX EQUITY is also indicated for the immediate reversal of neuromuscular blockade at 3 minutes after administration of rocuronium. For the paediatric population SUGAMMADEX EQUITY is only recommended for routine reversal of rocuronium induced blockade in children above 7 years of age.

Posology: SUGAMMADEX EQUITY should be administered under the supervision of an anaesthetist. The use of an appropriate neuromuscular monitoring technique is recommended to monitor the recovery of the neuromuscular blockade. When certain medicines that may cause displacement interactions are administered parenterally within 7,5 hours of SUGAMMADEX EQUITY, patients should be monitored for signs of recurrence of neuromuscular blockade. The recommended dose of SUGAMMADEX EQUITY depends on the level of neuromuscular blockade to be reversed. The recommended dose does not depend on the anaesthetic regimen. SUGAMMADEX EQUITY can be used to reverse different levels of rocuronium or vecuronium induced neuromuscular blockade.

Routine reversal of neuromuscular blockade: A dose of 4 mg/kg SUGAMMADEX EQUITY is recommended if recovery has reached at least 1 u2013 2 post-tetanic counts (PTC) following rocuronium or vecuronium induced blockade (see section 4.4). A dose of 2 mg/kg SUGAMMADEX EQUITY is only recommended if spontaneous recovery has reached the reappearance of T2 (shallow blockade) following rocuronium or vecuronium induced blockade (see section 4.4).

Immediate reversal: If there is a clinical need for immediate reversal at 3 minutes following administration of rocuronium, a dose of 16 mg/kg SUGAMMADEX EQUITY is recommended. There is no data to recommend the use of SUGAMMADEX EQUITY for immediate reversal following vecuronium induced blockade.

Special populations: Renal impairment: For mild and moderate renal impairment (creatinine clearance u2265 30 and < 80 mL/min): The dose recommendations are the same as for adults without renal impairment. The use of SUGAMMADEX EQUITY in patients with severe renal impairment, including patients requiring dialysis (CrCI < 30 mL/min), is not recommended (see section 4.4). Studies in patients with severe renal impairment do not provide sufficient safety information to support the use of SUGAMMADEX EQUITY in these patients.

Elderly patients: After administration of SUGAMMADEX EQUITY at reappearance of T2 following a rocuronium induced blockade, the median time to recovery of the T4/T1 ratio to 0,9 in adults (18 to 64 years) was 2,2 minutes; in elderly adults (65 to 74 years) it was 2,6 minutes and in very elderly adults (75 years or more) it was 3,6 minutes. Even though the recovery times in elderly patients tend to be slower, the same dose recommendation as for adults should be followed (see section 4.4).

Obese patients: In obese patients, the dose of SUGAMMADEX EQUITY should be based on actual body weight. The same dose recommendations as for adults should be followed.

Hepatic impairment: For mild to moderate hepatic impairment: As SUGAMMADEX EQUITY is mainly excreted renally no dose adjustments are required. Studies in patients with hepatic impairment have not been conducted. Caution should be exercised when considering the use of SUGAMMADEX EQUITY in patients with severe hepatic impairment or when hepatic impairment is accompanied by coagulopathy (see section 4.4).

Paediatric population: The data for the paediatric population are limited. There is insufficient information on the use of SUGAMMADEX EQUITY for children < 7 years of age. There is no information on SUGAMMADEX EQUITY use for neonates. Therefore, SUGAMMADEX EQUITY is not recommended for use in these populations. Children and adolescents: For routine reversal of rocuronium induced blockade at reappearance of T2 in children and adolescents (7 to 17 years) 2 mg/kg SUGAMMADEX EQUITY is recommended. Immediate reversal in children and adolescents has not been investigated and is therefore not recommended. SUGAMMADEX EQUITY 100 mg/mL may be diluted to 10 mg/mL to increase the accuracy of dosing in the paediatric population, 7 years and older.

Method of administration: SUGAMMADEX EQUITY should be administered intravenously as a single bolus injection. The bolus injection may be given rapidly, within 10 seconds, directly into a vein or into an existing IV line. For information on compatibility of SUGAMMADEX EQUITY with infusion solutions, see section 6.6.

Hypersensitivity to sugammadex sodium or to any of the components of SUGAMMADEX EQUITY (see section 6.1).

SUGAMMADEX EQUITY is not to be used to reverse depolarising neuromuscular blocking medicines. Wating times for re-administration with non-depolarising neuromuscular blocking medicines (NMBM) after reversal with SUGAMMADEX EQUITY. Re-administration of rocuronium or vecuronium after a recommended dose reversal (up to 4 mg/kg of SUGAMMADEX EQUITY): Minimum waiting time NMBM 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. When rocuronium 1,2 mg/kg is administered within 30 minutes after reversal with SUGAMMADEX EQUITY, 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 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 EQUITY 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 EQUITY): A waiting time of 24 hours is recommended. If neuromuscular blockade is required before the recommended waiting time has passed, a nonsteroidal neuromuscular blocking medicine should be used. The onset of a depolarising neuromuscular blocking medicine might be slower than expected, because a substantial fraction of post-junctional nicotinic receptors may still be occupied by the neuromuscular blocking medicine.

Medicine hypersensitivity: Medical practitioners should be prepared for the possibility of medicine hypersensitivity reactions (including anaphylactic reactions) and take the necessary precautions.

Renal impairment: SUGAMMADEX EQUITY is not recommended for use in patients with severe renal impairment, creatinine clearance < 30 mL/min, including patients requiring dialysis (see section 5.2). Because of the estimated prolonged half-life of sugammadex in severe renally impaired patients, a full neuromuscular blockade may not be achieved after re-use of 0,6 mg/kg rocuronium or 0,1 mg/kg vecuronium within 24 hours after SUGAMMADEX EQUITY reversal.

Marked bradycardia: Marked bradycardia has been observed within minutes after the administration of sugammadex, as in SUGAMMADEX EQUITY for reversal of neuromuscular blockade. Cases of bradycardia with cardiac arrest have been reported (see section 4.8). Patients should be closely monitored for haemodynamic changes during and after reversal of neuromuscular blockade. Treatment with anticholinergic medicines such as atropine should be administered if clinically significant bradycardia is observed.

Monitoring respiratory function during recovery: Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored following reversal of neuromuscular block. Even if recovery from neuromuscular blockade is complete, other medicines used in the peri- and post-operative period could depress respiratory function and therefore ventilatory support might still be required. Should neuromuscular blockade re-occur following extubation, adequate ventilation should be provided.

Effect on haemostasis: In a study in volunteers, doses of 4 mg/kg and 16 mg/kg of sugammadex, as in SUGAMMADEX EQUITY 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 (u2264 30 minutes). 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 patients receiving 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. In in-vitro experiments additional aPTT and PT prolongation was noted for sugammadex, as in SUGAMMADEX EQUITY in combination with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran. Patients with known coagulopathies and in patients who receive a dose of 16 mg/kg sugammadex, coagulation parameters should be carefully monitored according to routine clinical practice.

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 patients), or oedematous state (e.g. severe hepatic impairment) may be associated with longer recovery times.

Hepatic impairment: SUGAMMADEX EQUITY is not metabolised nor excreted by the liver; therefore dedicated studies in patients with hepatic impairment have not been conducted. Hepatic impairment may be accompanied by coagulopathy (see the information on the Effect on haemostasis above).

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 sucking 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.

Use in intensive care unit: SUGAMMADEX EQUITY has not been investigated in patients receiving rocuronium or vecuronium in the ICU setting.

Use for reversal of neuromuscular blocking medicines other than rocuronium or vecuronium: SUGAMMADEX EQUITY should not be used to reverse block induced by nonsteroidal neuromuscular blocking medicines such as succinylcholine or benzylisoquinolinium compounds. SUGAMMADEX EQUITY should not be used for reversal of neuromuscular blockage induced by steroidal neuromuscular blocking medicines 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 blockage, but it is advised not to use SUGAMMADEX EQUITY in this situation.

The information reported in this section is based on binding affinity between sugammadex and other medicines, non-clinical experiments, clinical studies and simulations using a model taking into account the pharmacodynamic effect of neuromuscular blocking medicines and SUGAMMADEX EQUITY. Based on these data, no clinically significant pharmacodynamic interaction with other medicines are expected, with the exception of toremifene, fusidic acid and hormonal contraceptives. For these medicines, a clinically relevant interaction could not be excluded. No clinically relevant interactions were reported during the clinical development. Due to the administration of certain medicines after sugammadex, theoretically rocuronium or vecuronium could be displaced from SUGAMMADEX EQUITY. As a result, recurrence of neuromuscular blockade might be observed. In this situation the patient must be ventilated. Administration of medicines 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 re-occurrence of blockade (approximately up to 15 minutes), after parenteral administration of another medicine occurring within a period of 7,5 hours after SUGAMMADEX EQUITY administration.

SUGAMMADEX EQUITY should be used cautiously when co-administered with:

• Toremifene: For toremifene, which has a relatively high affinity constant and relatively high plasma concentrations, some displacement of vecuronium or rocuronium from the complex with SUGAMMADEX EQUITY could occur. The recovery of the train of four ratio, T4/T1, to 0,9 could therefore be delayed in patients who have received toremifene on the same day of surgery (see section 4.4).
• Intravenous administration of fusidic acid: The use of fusidic acid in the pre-operative phase may cause 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 to 3 days.
• Hormonal contraceptives: In a simulation performed with a PK-PD model, it was found that the interaction between 4 mg/kg SUGAMMADEX EQUITY and a progestogen could 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. Therefore, the administration of a bolus dose of SUGAMMADEX EQUITY is considered to be equivalent to one missed daily dose of oral contraceptive steroids. Please refer to the missed dose advice in the package insert of the oral contraceptive, for any action required if an oral contraceptive is taken on the same day that SUGAMMADEX EQUITY is administered. In the case of non-oral hormonal contraceptives, the patient must use an additional non-hormonal contraceptive method for the next 7 days.

Interactions due to the lasting effect of rocuronium or vecuronium: When medicines 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 professional information of rocuronium or vecuronium for a list of the specific medicines which potentiate neuromuscular blockade.

Interference with laboratory tests: SUGAMMADEX EQUITY has been shown to interfere with the serum progesterone assay. This interference was observed in plasma samples spiked with a concentration of SUGAMMADEX EQUITY in the same range as obtained for Cmax after a dose of 16 mg/kg.

Paediatric population: No formal interaction studies have been performed. The above-mentioned interactions for adults and the warnings should also be taken into account for the paediatric population.

Pregnancy: The safety of SUGAMMADEX EQUITY in pregnant women has not been established.

Breastfeeding: Excretion of SUGAMMADEX EQUITY in human milk has not been studied, but can be expected based on pre-clinical data. Caution should be exercised when administering SUGAMMADEX EQUITY to breastfeeding women.

Fertility: The effects of SUGAMMADEX EQUITY on human fertility has not been investigated. Animal studies to evaluate fertility do not reveal harmful effects.

SUGAMMADEX EQUITY has no influence on the ability to drive and use machines. Patients should not drive, use machinery, or perform tasks that require concentration until they are certain that SUGAMMADEX EQUITY does not adversely affect their ability to do so safely (see section 4.8).

Tabulated list of adverse reactions:

• Immune system disorders: Less frequent: Medicine hypersensitivity reactions
• Nervous system disorders: Frequent: Dysgeusia
• Respiratory, thoracic and mediastinal disorders: Frequent: Cough
• Injury, poisoning and procedural complications: Frequent (with sub-optimal doses): Prolonged neuromuscular blockade
• Frequent: Anaesthetic complication, Airway complication of anaesthesia, Procedural hypotension, Procedural complication.

Description of selected adverse reactions:

Airway complication of anaesthesia: 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 contra breath (spontaneous breath of patient, anaesthetic procedure related).

Procedural complication: Procedural complications included coughing, tachycardia, bradycardia, movement and increase in heart rate.

Anaesthetic complications: Anaesthetic complications, indicative of the restoration of neuromuscular function, including movement of a limb or the body or coughing during the anaesthetic procedure or during surgery, grimacing, or sucking on the endotracheal tube, were judged to be related to treatment in about 1 % of the patients and in none of the placebo group. Most occurrences of anaesthetic complications were mild to moderate.

Recurrence of neuromuscular blockade: In clinical studies with patients treated with rocuronium or vecuronium, where sugammadex (as in SUGAMMADEX EQUITY) 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. In cases where recurrence of neuromuscular blockade is observed, the patient must be ventilated.

Medicine hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have occurred in some patients and volunteers (for information on volunteers, see Information on healthy volunteers below). 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 EQUITY. Symptoms associated with these reactions can include: Flushing, urticaria, erythematous rash, (severe) hypotension, tachycardia, swelling of the tongue, swelling of the pharynx, bronchospasm and pulmonary obstructive events. Severe hypersensitivity reactions can be fatal.

Information on healthy volunteers: Hypersensitivity reactions, including anaphylaxis, have been observed with SUGAMMADEX EQUITY. In a study in healthy volunteers, hypersensitivity reactions were reported frequently with sugammadex 16 mg/kg and less frequently with sugammadex 4 mg/kg or placebo. The most common adverse reaction in pooled healthy volunteers was dysgeusia (10 %).

Marked bradycardia: In post-marketing, cases of marked bradycardia and bradycardia with cardiac arrest have been observed within minutes after administration of sugammadex (see section 4.4).

Additional information on special populations: Pulmonary patients: 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.

Paediatric patients: A limited database suggests that the safety profile of sugammadex (up to 4 mg/kg) in paediatric patients above 7 years old, was similar to that in adults.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of SUGAMMADEX EQUITY is important. It allows continued monitoring of the benefit/risk balance of SUGAMMADEX EQUITY. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRAu2019s website.

SUGAMMADEX EQUITY can be removed using haemodialysis with a high-flux filter, but not with a low-flux filter. Based upon clinical studies, SUGAMMADEX EQUITY concentrations in plasma are reduced with a high-flux filter by about 70 % after a 3 to 6 hour dialysis session.