Manufacturer: Merck FDA Approval Date: December 15, 2015 Bridion® - Sugammadex Manufacturer: Merck FDA Approval Date: December 15, 2015

Bridion® - Sugammadex Objectives At the end of this presentation participants will be able to: Appropriately recommend Bridion® - Sugammadex Effectively educate patients on the purpose, proper use and potential adverse effects of Bridion® - Sugammadex

Bridion® - Sugammadex Clinical Application Indications: Used for adults undergoing surgery for the reversal of neuromuscular blockade (NMB) induced by rocuronium or vecuronium Not indicated to reverse blockade of nonsteroidal neuromuscular blocking agents (eg, succinylcholine) Not indicated for use in ICU setting Bridion® [package insert].

Bridion® - Sugammadex Clinical Application Contraindications: Hypersensitivity to sugammadex or any component of the product Precautions: Use not recommended with severe renal impairment or dialysis-dependent patients Caution with mild-to-moderate renal impairment (no dosage adjustment) Bridion® [package insert].

Bridion® - Sugammadex Clinical Application Pregnancy: No available human data In animal studies, fetal birthweight was reduced when 8x human dose was administered Lactation: Unknown excretion in human breast milk Present in animal milk Bridion® [package insert].

Bridion® - Sugammadex Drug Facts Mechanism of Action Cyclodextrin that forms a 1:1 complex with rocuronium and vecuronium This reduces the amount of free NMB agent in plasma In turn, the concentration gradient favors movement of NMB agent away from the neuromuscular junction Bridion® [package insert].

Bridion® - Sugammadex Drug Facts Drug Interactions: Hormonal contraceptives: must recommend additional, non-hormonal method of contraception for next 7 days Toremifene: recovery can be delayed Bridion® [package insert].

Bridion® - Sugammadex Adverse Effects Side effects are dose-dependent Common (2-4 mg/kg) {16 mg/kg} [placebo]: Nausea (23%) {26%} [23%] Vomiting (11%) {15%} [10%] Serious (2-4 mg/kg) {16 mg/kg} [placebo]: Prolonged QT interval (1%) {6%} [1%] Bradycardia (1%) {5%} [1%] Hypotension (4%) {13%} [4%] Anaphylaxis (0%) {1%} [0%] Bridion® [package insert].

Bridion® - Sugammadex Dosing Information 2-4 mg/kg IV bolus based on actual body weight depending on blockade status Immediate Reversal: 16 mg/kg IV bolus based on actual body weight This dose has only been studied for rocuronium reversal Bridion® [package insert].

Bridion vs. neostigmine reversal agent for NMB induced by rocuronium or vecuronium at reappearance of T2 (Moderate Blockade) Eur J Anaesthesiol 2001;18:99 -Randomized, single-dose, active-controlled, safety-assessor blinded trial of 198 patients (adults scheduled for surgery under general anesthesia in the supine position) -Efficacy of sugammadex compared with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs) -Primary outcome: Time to a train of four ratio (T4/T1) of 0.9

Purpose: Comparing the efficacy of sugammadex with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs Design: Randomized, single-dose, active-controlled, safety-assessor blinded trial of 98 patients Sugammadex 2.0mg/kg or neostigmine 50 μg/kg plus glycopyrrolate 10 μg/kg were administered intravenously in randomized order -Randomized, single-dose, active-controlled, safety-assessor blinded trial of 198 patients (adults scheduled for surgery under general anesthesia in the supine position) -Efficacy of sugammadex compared with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs) - Blobner M, et al. Eur J Anaesthesiol. 2001;18:99.

Primary outcome: Recovery time after reversal agent administration Included: Adult patients scheduled for surgery under general anesthesia in the supine position > 18 years old ASA class 1 to 3 Primary outcome: Recovery time after reversal agent administration measured as train of four ratio (T4/T1) of 0.9 -Randomized, single-dose, active-controlled, safety-assessor blinded trial of 198 patients (adults scheduled for surgery under general anesthesia in the supine position) -Efficacy of sugammadex compared with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs) - Blobner M, et al. Eur J Anaesthesiol. 2001;18:99.

Adverse effects were not attributed to the study drug Serious adverse effects were reported for 2 subjects in the sugammadex group and 3 in the neostigmine group Adverse effects were not attributed to the study drug -Randomized, single-dose, active-controlled, safety-assessor blinded trial of 198 patients (adults scheduled for surgery under general anesthesia in the supine position) -Efficacy of sugammadex compared with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs) - Blobner M, et al. Eur J Anaesthesiol. 2001;18:99.

Sugammadex achieved significantly faster recovery of T4/T1 ratio to 0 Sugammadex achieved significantly faster recovery of T4/T1 ratio to 0.9 compared with neostigmine after neuromuscular block with rocuronium Outliers and variability of recovery times were significantly lower following reversal with sugammadex -Randomized, single-dose, active-controlled, safety-assessor blinded trial of 198 patients (adults scheduled for surgery under general anesthesia in the supine position) -Efficacy of sugammadex compared with neostigmine given with glycopyrrolate or atropine in antagonizing block produced by aminosteroidal NMBAs) - Blobner M, et al. Eur J Anaesthesiol. 2001;18:99.

Bridion® - Sugammadex Cost Comparison Neuromuscular Blocking and Reversal Agents AWP Pricing Sugammadex 200 mg/2 ml SDV $1140 Sugammadex 500 mg/5 ml SDV $2088 Neostigmine (Bloxiverz) 1 mg/ml 10 ml MDV $1185 Pyridostigmine (Regonol) 5 mg/ml 2ml Vial $384 Glycopyrrolate (Robinul) 0.2 mg/ml SDV $390 AWP pricing as of 2/26/2016

Bridion® - Sugammadex Summary Bridion, sugammadex, is first-in-class cyclodextrin that directly reverses neuromuscular blockade It is indicated for the reversal of neuromuscular blockade for rocuronium and vecuronium for patients undergoing surgical procedures only Dosed: 2-4 mg/kg IV bolus based on total body weight OR 16 mg/kg IV bolus reserved for emergent reversal Offers faster reversal times compared to neostigmine All women of child bearing age should be counseled on using backup contraception for 7 days post-op It is not cost prohibitive, but is more expensive than neostigmine

Bridion® - Sugammadex References www.bridion.com Bridion package insert. Merck. Dec. 2015. Blobner M, Eriksson L, Scholz J, Hillebrand H, Pompei L. Sugammadex (2.0 mg/kg) significantly faster reverses shallow rocuronium-induced neuromuscular blockade compared with neostigmine (50 µg/kg). Eur J Anaesthesiol 2001;18:99.

Bridion® - Sugammadex References 4. Sugammadex: DrugDex. (2016). In Micromedex (Columbia Basin College Library ed.)  [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved March 21, 2016 from http://www.micromedexsolutions.com/ 5. Neostigmine: DrugDex. (2016). In Micromedex (Columbia Basin College Library ed.)  [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved March 21, 2016 from http://www.micromedexsolutions.com/