SUGAMMADEX

1 Dosing Considerations • Sugammadex Injection should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents.

• Doses and timing of Sugammadex Injection administration should be based on monitoring for twitch responses and the extent of spontaneous recovery that has occurred. • The recommended dose of Sugammadex Injection does not depend on the anesthetic regimen, but rather on the level of neuromuscular blockade to be reversed.

The anesthetic regimen may affect the recovery of the respiratory function and the reversal of the neuromuscular blockade independent of the reversal with Sugammadex Injection. • The use of Sugammadex Injection to reverse neuromuscular blockade induced by other steroidal neuromuscular blockers is not recommended.

g. atracurium and cisatracurium). 2 Recommended Dose and Dosage Adjustment • Pediatrics (birth-17 years of age): As for adults, the dose calculation is based on actual body weight. A dose of 2 mg/kg Sugammadex Injection is recommended when spontaneous recovery has reached the reappearance of T2 (moderate blockade) following rocuronium or vecuronium induced neuromuscular blockade.

A dose of 4 mg/kg Sugammadex Injection is recommended for reversal of rocuronium or vecuronium induced blockade if spontaneous recovery has reached at least 1-2 post- tetanic counts (PTC), and there is no twitch response to train-of-four (TOF) stimulation (deep blockade).

Immediate reversal has not been studied in the pediatric population. Doses higher than 4 mg/kg are not recommended for routine reversal of neuromuscular blockade as they may be associated with higher incidence of hypersensitivity and other adverse reactions.

9. 2 CLINICAL PHARMACOLOGY, Pharmacodynamics). 0 mg/kg Sugammadex Injection is recommended when spontaneous recovery has reached the reappearance of T2 (moderate blockade) following rocuronium or vecuronium induced neuromuscular blockade.

0 mg/kg Sugammadex Injection is recommended for reversal of rocuronium or vecuronium induced blockade if spontaneous recovery has reached at least 1-2 post-tetanic counts (PTC), and there is no twitch response to train-of-four (TOF) stimulation (deep blockade) following administration of rocuronium or vecuronium induced neuromuscular blockade.

A dose higher than 4 mg/kg Sugammadex Injection is not recommended for routine reversal of neuromuscular blockade induced by rocuronium or vecuronium, as it has not been studied and is possibly associated with higher incidence of hypersensitivity reactions.

2 mg/kg rocuronium for intubation. The efficacy of 16 mg/kg sugammadex for such use was studied in surgical patients without airway emergency. The efficacy of the 16 mg/kg dose of sugammadex injection following administration of vecuronium has not been studied (see 10 CLINICAL PHARMACOLOGY).

This dose is associated with a 1-2% risk of an anaphylaxis in addition to higher frequencies of other less serious hypersensitivity reactions in studies of healthy volunteers (see 10 CLINICAL PHARMACOLOGY). • Waiting Times for Re-Administration of Neuromuscular Blocking Agents for Intubation Following Reversal with Sugammadex Injection: A minimum waiting time is necessary before administration of a steroidal neuromuscular blocking agent after administration of Sugammadex Injection.

Recommendations are based upon a clinical study in healthy volunteers and simulations from a PK-PD model; the actual clinical patient response may vary significantly (see 10 CLINICAL PHARMACOLOGY). If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent.

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. For re-administration of rocuronium and vecuronium, the suggested minimum waiting time is outlined in the table below.

2 mg/kg is administered within 30 minutes after reversal with Sugammadex Injection, 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.

For re-administration of rocuronium or administration of vecuronium after reversal of rocuronium with 16 mg/kg Sugammadex Injection, a waiting time of 24 hours is suggested. • Renal Impairment: Sugammadex Injection is not recommended for use in patients with severe (CrCl <30 mL/min) renal impairment including those requiring dialysis (see 7 WARNINGS AND PRECAUTIONS).

No dose […]

, Clinical Trial Adverse Reactions). 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • Sugammadex Injection should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents.

• Sugammadex Injection may cause hypersensitivity reactions, including anaphylaxis or anaphylactoid reactions, on first or subsequent exposure. 2 ADVERSE REACTIONS, Clinical Trial Adverse Reactions). 1 Dosing Considerations • Sugammadex Injection should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents.

• Doses and timing of Sugammadex Injection administration should be based on monitoring for twitch responses and the extent of spontaneous recovery that has occurred. • The recommended dose of Sugammadex Injection does not depend on the anesthetic regimen, but rather on the level of neuromuscular blockade to be reversed.

The anesthetic regimen may affect the recovery of the respiratory function and the reversal of the neuromuscular blockade independent of the reversal with Sugammadex Injection. • The use of Sugammadex Injection to reverse neuromuscular blockade induced by other steroidal neuromuscular blockers is not recommended.

g. atracurium and cisatracurium). 2 Recommended Dose and Dosage Adjustment • Pediatrics (birth-17 years of age): As for adults, the dose calculation is based on actual body weight. A dose of 2 mg/kg Sugammadex Injection is recommended when spontaneous recovery has reached the reappearance of T2 (moderate blockade) following rocuronium or vecuronium induced neuromuscular blockade.

A dose of 4 mg/kg Sugammadex Injection is recommended for reversal of rocuronium or vecuronium induced blockade if spontaneous recovery has reached at least 1-2 post- tetanic counts (PTC), and there is no twitch response to train-of-four (TOF) stimulation (deep blockade).

Immediate reversal has not been studied in the pediatric population. Doses higher than 4 mg/kg are not recommended for routine reversal of neuromuscular blockade as they may be associated with higher incidence of hypersensitivity and other adverse reactions.

9. 2 CLINICAL PHARMACOLOGY, Pharmacodynamics). 0 mg/kg Sugammadex Injection is recommended when spontaneous recovery has reached the reappearance of T2 (moderate blockade) following rocuronium or vecuronium induced neuromuscular blockade.

0 mg/kg Sugammadex Injection is recommended for reversal of rocuronium or vecuronium induced blockade if spontaneous recovery has reached at least 1-2 post-tetanic counts (PTC), and there is no twitch response to train-of-four (TOF) stimulation (deep blockade) following administration of rocuronium or vecuronium induced neuromuscular blockade.

A dose higher than 4 mg/kg Sugammadex Injection is not recommended for routine reversal of neuromuscular blockade induced by rocuronium or vecuronium, as it has not been studied and is possibly associated with higher incidence of hypersensitivity reactions.

2 mg/kg rocuronium for intubation. The efficacy of 16 mg/kg sugammadex for such use was studied in surgical patients without airway emergency. The efficacy of the 16 mg/kg dose of sugammadex injection following administration of vecuronium has not been studied (see 10 CLINICAL PHARMACOLOGY).

This dose is associated with a 1-2% risk of an anaphylaxis in addition to higher frequencies of other less serious hypersensitivity reactions in studies of healthy volunteers (see 10 CLINICAL PHARMACOLOGY). • Waiting Times for Re-Administration of Neuromuscular Blocking Agents for Intubation Following Reversal with Sugammadex Injection: A minimum waiting time is necessary before administration of a steroidal neuromuscular blocking agent after administration of Sugammadex Injection.

Recommendations are based upon a clinical study in healthy volunteers and simulations from a PK-PD model; the actual clinical patient response may vary significantly (see 10 CLINICAL PHARMACOLOGY). If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent.

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. For re-administration of rocuronium and vecuronium, the suggested minimum waiting time is outlined in the table below.

Page 8 of 49Sugammadex Injection (sugammadex sodium) Protected B / Protégé B Table 2: Re-administration of rocuronium or vecuronium after routine reversal (up to 4 mg/kg Sugammadex Injection) […]

, Hypersensitivity Reactions; 8.

Sugammadex Injection is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

e. anaphylaxis, or anaphylactic reactions), have occurred in individuals with or without prior exposure to sugammadex (see