Please refer to the accompanying full Prescribing Information.

EXPAREL is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene

brachial plexus nerve block to produce postsurgical regional analgesia. Safety and efficacy have not been

established in other nerve blocks.

PILLAR CLINICAL TRIALQUICK REFERENCE GUIDE

WAS TO ASSESS THE

SAFETY & EFFICAC Y of EXPAREL vs bupivacaine HCl

in Total Knee Arthroplasty using STANDARDIZED volume, technique, and

protocol in both the study and control groups

THE OBJECTIVE OF THE

PILLAR STUDY

Please see Important Safety Information and accompanying full Prescribing Information. 32

PILLARSTUDY DESIGN1

(NCT02713490)

16 study sites in the United States enrolled 139 patients

All patients were required to stay in the hospital for 48 hours post-op to capture all data required to assess primary endpoints

All surgeons were trained on and required to follow a standard infiltration technique and protocol as described in the published administration protocol for TKAs

Double-blind

139 adult patients underwent a

primary unilateral TKAR

AN

DO

MIZ

ATI

ON

1:1

EXPAREL Local infiltration with: 266 mg/20 mL EXPAREL + 20 mL 0.5% bupivacaine HCl + 80 mL saline

= 120 mL TOTAL volume

CONTROL GROUP Local infiltration with: 20 mL 0.5% bupivacaine HCl + 100 mL saline

= 120 mL TOTAL volume

PHASE IV

n=70

n=69

PRIMARY ENDPOINTS1

SECONDARY ENDPOINTS

Area under the curve (AUC) of visual analog scale (VAS) pain intensity scores 12 to 48 hours post-op

Total opioid consumption 0 to 48 hours post-op

AUC VAS pain scores through 72 hours

% of patientsopioid freethrough 72 hours

Opioid consumption through 72 hours

Time to first opioid rescue through 72 hours

Important Safety Information

EXPAREL is contraindicated in obstetrical paracervical block anesthesia.

Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation.

If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine.

EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients.

Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease.

Warnings and Precautions Specific to EXPARELAvoid additional use of local anesthetics within 96 hours following administration of EXPAREL.

EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks other than interscalene brachial plexus nerve block, or intravascular or intra-articular use.

The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials.

Please see Important Safety Information and accompanying full Prescribing Information. 54

RESULTS1

EXPAREL® (bupivacaine liposome injectable suspension) compared with bupivacaine HCl

Using the PILLAR protocol and administration technique, surgeons were able to achieve consistently favorable outcomes1

TOTAL OPIOID CONSUMPTION0 to 48 hours

FEWER OPIOIDSin EXPAREL group*

78%P=0.0048

EXPAREL Bupivacaine HCl

90

60

30

0

18.7 mg

48-Hour Opioid Consumption (mg)

84.9 mg

Important Safety Information, continued

Warnings and Precautions for Bupivacaine-Containing Products, continuedAllergic Reactions: Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients.

Chondrolysis: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use.

Methemoglobinemia: Cases of methemoglobinemia have been reported with local anesthetic use.

PAIN INTENSITY SCORESAUC of VAS pain intensity scores

12 to 48 hours

LESS PAINin EXPAREL group

13.6%P=0.0381

EXPAREL Bupivacaine HCl

209.3

180.8

Cumulative AUC VAS Pain Score

210

157.5

105

52.5

0

Rates and types of adverse events were similar between treatment groups. The most common adverse events in the EXPAREL group were nausea,

muscle spasms, and vomiting.

of patients in the EXPAREL group were

through the first 72 hours following surgery compared with 0% of patients who received bupivacaine HCl alone(P=0.01)

PREOPERATIVE & POSTOPERATIVE

MEDICATIONS AIDED OPIOID MINIMIZATION IN THE PILLAR STUDY1

Scheduled preoperative medications:

• Oral acetaminophen (eg, TYLENOL®) 1000 mg

• Oral celecoxib 200 mg

• Oral pregabalin 300 mg

• IV tranexamic acid 1 g

• Oral acetaminophen (eg, TYLENOL®) 975 to 1000 mg every 8 hours

• Oral celecoxib 200 mg every 12 hours

Rescue opioids permitted for breakthrough pain postoperatively, including:

• Oral oxycodone <10 mg every 4 hours as needed

• IV morphine 2.5 to 5.0 mg every 4 hours as needed

• Hydromorphone 0.5 to 1.0 mg every 4 hours as needed

4 hours pre-op1

Intra-op*

Post-op pain meds1

Bupivacaine HCl

Important Safety Information, continued

Warnings and Precautions for Bupivacaine-Containing Products

Central Nervous System (CNS) Reactions: There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression.

Cardiovascular System Reactions: Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death.

*Patient received either a single shot spinal approach or general anesthesia.

EXPAREL® (bupivacaine liposome injectable suspension) 266 mg/20 mL + 20 mL 0.5% bupivacaine HCl + 80 mL saline

20 mL 0.5% bupivacaine HCl + 100 mL saline

*The clinical benefit of the decrease in opioid consumption was not demonstrated in the pivotal trials.

Please see Important Safety Information and accompanying full Prescribing Information. 76

Adapted with permission; International Guidelines Center (guidelinecentral.com) – Erin Daniel, illustrator.

PILLAR PROTOCOL AND TECHNIQUE1

The PILLAR protocol highlights an appropriate infiltration technique, optimal targeting of tissue sites, and adequate volume expansion in TKA1

Consistent volume (120 mL) mixed with free bupivacaine HCl

Consistent infiltration protocol at anatomical sites with high nerve density

Consistent infiltration technique (1 to 1.5 mL volume spaced 1 to 1.5 cm apart)

Opioid-minimizing multimodal pain management protocol following surgery

Preoperative

• Patients receive acetaminophen (eg, TYLENOL®) 1000 mg + celecoxib 200 mg + pregabalin 300 mg and IV tranexamic acid 1 g within 4 hours of surgery

To achieve optimal analgesia, it is suggested to administer EXPAREL using1:

Intraoperative

EXPAREL

• All participants have access to rescue opioids as needed, including oral oxycodone ≤10 mg every 4 hours or IV morphine every 4 hours

Postoperative

• Patients receive oral acetaminophen (eg, TYLENOL®) 975 to 1000 mg as needed every 8 hours + celecoxib 200 mg as needed every 12 hours until discharge

10%of patients opioid-free

through 72 hours1

78%reduced opioidconsumption1

Long-lastingpain control2

Broad indicationfor infiltration

Unique multivesicular formulation

EXPAREL® (bupivacaine liposome injectable suspension)

DEMONSTRATED

13.6%lower pain

intensity scores1

Demonstrated in Phase IV TKA PILLAR Clinical Trial compared to bupivacaine HCl

Prior to Cementation

Syringe #1

• Posterior capsule (8-10 sticks medial and 8-10 sticks lateral)

Syringe #2

• Femur – medial and lateral periosteum, posterior periosteum, suprapatellar/quadriceps tendon

Syringe #3

• Tibia – fat pad (5 sticks)

• Pes anserinus, medial collateral ligament, and gutter (15 sticks)

Syringe #4

• Circumferential periosteum (15-20 sticks)

After Cementation

Syringe #5

• Midline quadriceps tendon (10 sticks)

• Retinaculum, medial gutter, femoral to tibial (10 sticks)

Syringe #6

• Lateral gutter, femoral to tibial (10 sticks)

• Subcutaneous/closure (10 sticks)

Important Safety InformationEXPAREL is contraindicated in obstetrical paracervical block anesthesia.

Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation.

If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine.

EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients.

Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease.

Warnings and Precautions Specific to EXPARELAvoid additional use of local anesthetics within 96 hours following administration of EXPAREL.

EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks other than interscalene brachial plexus nerve block, or intravascular or intra-articular use.

The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials.

Warnings and Precautions for Bupivacaine-Containing ProductsCentral Nervous System (CNS) Reactions: There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression.

Cardiovascular System Reactions: Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death.

Allergic Reactions: Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients.

Chondrolysis: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use.

Methemoglobinemia: Cases of methemoglobinemia have been reported with local anesthetic use.

Please refer to accompanying full Prescribing Information.

References1. Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local infiltration analgesia with

liposomal bupivacaine improves pain scores and reduces opioid use after total knee arthroplasty: results of a randomized controlled trial. J Arthroplasty. 2018;33(1):90-96.

2. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011;54(12):1552-1559.

EXPAREL® (bupivacaine liposome injectable suspension)

www.EXPAREL.com/pillar

Please contact your DePuy Synthes Sales Consultant for more information.

For complete information related to EXPAREL,call 1-855-RX-EXPAREL (793-9729) or visit www.EXPAREL.com.

PP-EX-US-3727 03/19 103455-181130 DSUSThe third-party trademarks used herein are the trademarks of their respective owners.

© Pacira Pharmaceuticals, Inc. © J & J Consumer Inc. © DePuy Synthes 2019. All rights reserved.