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days to go: ASP+6% CMS reimbursement for proven non-opioids used in all outpatient surgical settings is coming January 1, 2025.

Dosing for local infiltration

Dosing for local infiltration

For adults, a maximum dose of 266 mg (20 mL) is recommended, based on:

  • Size of the surgical site
  • Volume required to cover the area
  • Individual patient factors that may impact the safety of an amide local anesthetic

For pediatric patients aged 6 to less than 17 years, dosing is weight based: 4 mg/kg (up to a maximum of 266 mg)

Admixing bupivacaine HCl with 266 mg (20 mL) of EXPAREL

  • 20 mL vial contains 266 mg of EXPAREL, which is equivalent to 300 mg of bupivacaine HCl
  • 1:2 ratio allows 150 mg of bupivacaine HCl to 266 mg of EXPAREL
Expansion Techniques
Administration Guidance
dosing 266

Approved for postsurgical pain management in pediatrics

The first and only FDA-approved long-lasting local analgesic for ages 6 and above.1 Demonstrated in PLAY, a clinical trial centered uniquely on safety in children.2 Pediatric patients in the EXPAREL study were defined as 6 to <17 years of age.

Study Design
Download IconRead the Tirotta PLAY study

The PLAY study was designed to establish the safety and pharmacokinetics (PK) of EXPAREL in pediatric patients3

A multicenter, open-label, phase 3 trial with 2 parts including pediatric patients 6 to <17 years of age

study design teen silo

Age Group 1 12 to <17 years old Spine surgery

n=61

Local infiltration

  • EXPAREL 4 mg/kg* n=31
  • n=16 with PK data
  • Bupivacaine HCl 2 mg/kg† n=30
  • n=15 with PK data

Blood samples collected from 0.25 to 60 hours after treatment

study design kid silo

Age Group 2 6 to <12 years old Spine or cardiac surgery

n=34

Local infiltration

Spine

Cardiac

  • EXPAREL 4 mg/kg* n=5
  • n=2 with PK data
  • EXPAREL 4 mg/kg* n=29
  • n=21 with PK data

Blood samples collected 0.25 to 60 hours after treatment for spine surgery, 0.25 to 72 hours after treatment for cardiac surgery

Study End Points

Part 1: PK and safety

Part 2: Long-term safety

  • AEs up to 30 days after surgery
  • Neurologic assessments
  • Clinical laboratory tests
  • Vital signs

Baseline characteristics were generally comparable among groups.

*Maximum total dose of 266 mg.

†Maximum total dose of 175 mg.

The safety of EXPAREL was comparable to bupivacaine and consistent across treatment groups

EXPAREL was well tolerated for all age groups, with TEAEs being mild or moderate and no discontinuations3

Overview of TEAEs With EXPAREL Greater Than or Equal to 10%
Patients aged 6 to <17 years old Patients aged 6 to <12 years old
Spine surgery EXPAREL 4 mg/kg; n=36 (%) Cardiac surgery EXPAREL 4 mg/kg; n=29 (%)
Vision blurred 7 (19.4) 1 (3.4)
Constipation 9 (25) 4 (13.8)
Nausea 11 (30.6) 2 (6.9)
Hypoesthesia oral 4 (11.1) 0
Vomiting 10 (27.8) 4 (13.8)
Anemia postoperative 5 (13.9) 0
Muscle spasms 4 (11.1) 0
Hypotension 4 (11.1) 0
There were no treatment-related cardiac or nervous system adverse events in the EXPAREL arms4

TEAE, treatment-emergent adverse event.

There is not enough evidence to determine if the numbers associated with spine surgery in patients aged 12 to <17 years old are indicative of differences in the surgery types.

Demonstrated safety with PK profiles that were well below toxic thresholds and bupivacaine PK levels3

The PK profile of EXPAREL in pediatric patients was:

  • Comparable across age groups
  • Generally consistent with the EXPAREL PK profile in adults

Group 1 PK Plot of Mean Concentrations (ng/mL) Over Time With EXPAREL and Bupivacaine3

group 1 pk chart v
  • Mean Cmax after EXPAREL administration in the spine surgery group combined was 353 ng/mL.
  • Mean Cmax after bupivacaine HCI administration in the spine surgery group was 488 ng/mL.3
  • Mean Cmax was 447 ng/mL after EXPAREL administration for cardiac surgery, with median time to Cmax occurring later vs the spine surgery group combined (23 hours vs 1.2 hours).

Cmax, maximum concentration.

The bupivacaine HCI data is for reference purposes only and does not reflect an active comparator in the study.

Demonstrated safety with PK profiles that were well below toxic thresholds and bupivacaine PK levels

The PK profile of EXPAREL in pediatric patients was:

  • Comparable across age groups
  • Generally consistent with the EXPAREL PK profile in adults

Group 2 PK Plot of Mean Concentrations (ng/mL) Over Time With EXPAREL3

group 2 pk chart v

  • Mean Cmax after EXPAREL administration in the spine surgery group combined was 353 ng/mL.
  • Mean Cmax after bupivacaine HCI administration in the spine surgery group was 488 ng/mL.3
  • Mean Cmax was 447 ng/mL after EXPAREL administration for cardiac surgery, with median time to Cmax occurring later vs the spine surgery group combined (23 hours vs 1.2 hours).

Cmax, maximum concentration.

The bupivacaine HCI data is for reference purposes only and does not reflect an active comparator in the study.

For children, a non-opioid option should be the only option

The risks and complications of adult-based pain management approaches may be magnified in children.5 Opioids, short-acting local anesthetics, and delivery devices are the mainstay despite safety implications and limited studies in children.5

Even so...

50% of children report moderate to severe pain in the hospital after surgery6

~20% of children report chronic pain 12 months after surgery6

Opioids can be attributed to 50% of postsurgical respiratory failure events in children and may also hinder recovery, extend hospital stay, and negatively impact both patient and parent experience.7-9

Potential side effects and complications with current modalities

Opioids5

  • Nausea/vomiting
  • Constipation
  • Urinary retention
  • Cognitive impairment
  • Dependence

Device-based platforms (ie, pumps and catheters)

  • Accidental removal10
  • Overdose11
  • Leakage12
  • Infection10
  • Unpredictability or malfunction10-12

Societies recommend opioid-minimizing pain management platforms

Medical societies recommend non-opioid analgesics and a multimodal approach to pain management for pediatric patients13

*This guideline was developed by the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee, in addition to a geographically diverse multidisciplinary team composed of leaders in pediatric opioid stewardship from academic and community hospitals and representatives from the American College of Surgeons (ACS) Education Committee, the American Academy of Pediatrics Section on Surgery, pediatric anesthesia, pediatric nursing, general surgery residency, pediatric surgery physician assistants, and addiction science.17

ASP, average sales price; CMS, Centers for Medicare and Medicaid Services.

Important Notice

Indication

EXPAREL® (bupivacaine liposome injectable suspension) is indicated to produce postsurgical local analgesia via infiltration in patients aged 6 years and older and regional analgesia in adults via an interscalene brachial plexus nerve block, sciatic nerve block in the popliteal fossa, and an adductor canal block. Safety and efficacy have not been established in other nerve blocks.

Important Safety Information

  • EXPAREL is contraindicated in obstetrical paracervical block anesthesia.
  • Adverse reactions reported in adults with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported in adults with an incidence greater than or equal to 10% following EXPAREL administration via nerve block were nausea, pyrexia, headache, and constipation.
  • Adverse reactions with an incidence greater than or equal to 10% following EXPAREL administration via infiltration in pediatric patients six to less than 17 years of age were nausea, vomiting, constipation, hypotension, anemia, muscle twitching, vision blurred, pruritus, and tachycardia.
  • Do not admix lidocaine or other non-bupivacaine local anesthetics with EXPAREL. EXPAREL may be administered at least 20 minutes or more following local administration of lidocaine.
  • EXPAREL is not recommended to be used in the following patient populations: patients <6 years old for infiltration, patients younger than 18 years old for nerve blocks, 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 EXPAREL

  • Avoid 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, sciatic nerve block in the popliteal fossa, and adductor canal 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 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.
  • 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 full Prescribing Information.

References

  1. US National Library of Medicine. Multicenter study for pediatric subjects evaluating pharmacokinetics and safety of EXPAREL (PLAY). https://clinicaltrials.gov/ct2/show/study/NCT03682302?term=exparel+pediatric&recrs=e&draw=2&rank=1 Accessed March 21, 2021.
  2. Pacira BioSciences. Pacira BioSciences announces FDA acceptance of sNDA for EXPAREL use in pediatric patients [press release]. https://investor.pacira.com/news-releases/news-release-details/pacira-announces-fda-approval-supplemental-new-drug-0 Accessed March 8, 2021.
  3. Tirotta CF, de Armendi AJ, Horn ND, et al. A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY). J Clin Anesth. 2021;75:11053.
  4. Data on File. 6539. Parsippany, NJ: Pacira BioSciences, Inc.; March 2021.
  5. Diwan R. Acute pain management: acute and chronic pain management in children. New York School of Regional Anesthesia [NYSORA]. Published July 8, 2018. https://www.nysora.com/topics/sub-specialties/pediatric-anesthesia/acute-chronic-pain-management-children/ Accessed October 7, 2024.
  6. Rabbitts JA, Fisher E, Rosenbloom BN, Palermo TM. Prevalence and predictors of chronic postsurgical pain in children: a systematic review and meta-analysis. J Pain. 2017;18(6):605-614.
  7. Chidambaran V, Sadhasivam S, Mahmoud M. Codeine and opioid metabolism: implications and alternatives for pediatric pain management. Curr Opin Anaesthesiol. 2017;30(3):349-356.
  8. Gandhi K, Viscusi E. Multimodal pain management techniques in hip and knee arthroplasty. J NYSORA. 2019;13(12):1-10.
  9. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician. 2001;63(10):1979-1984.
  10. Capdevila X, Pirat P, Bringuier S, et al; French Study Group on Continuous Peripheral Nerve Blocks. Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: a multicenter prospective analysis of the quality of postoperative analgesia and complications in 1,416 patients. Anesthesiology. 2005;103(5):1035-1045.
  11. Remerand F, Vuitton AS, Palud M, et al. Elastomeric pump reliability in postoperative regional anesthesia: a survey of 430 consecutive devices. Anesth Analg. 2008;107(6):2079-2084.
  12. Marhofer D, Marhofer P, Triffterer L, Leonhardt M, Weber M, Zeitlinger M. Dislocation rates of perineural catheters: a volunteer study. Br J Anaesth. 2013;111(5):800-806. c patients. Front Med (Lausanne). 2018;5(57):1-4.
  13. Modrzyk A, Pasierbek MJ, Korlacki W, Grabowski A. Introducing enhanced recovery after surgery protocol in pediatric surgery. Adv Clin Exp Med. 2020;29(8):937-942.
  14. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273.
  15. Cravero JP, Agarwal R, Berde C, et al. The Society for Pediatric Anesthesia recommendations for the use of opioids in children during the perioperative period. Ped Anesthesia. 2019;29:547-571.
  16. Kelley-Quon LI, Kirkpatrick MG, Ricca RL, et al. Guidelines for opioid prescribing in children and adolescents after surgery: an expert panel opinion. JAMA Surg. 2021;156(1):76-90.
SEE MORE

EXPAREL® (bupivacaine liposome injectable suspension) is indicated to produce postsurgical local analgesia via infiltration in patients aged 6 years and older and regional analgesia in adults via an interscalene brachial plexus nerve block, sciatic nerve block in the popliteal fossa, and an adductor canal block. Safety and efficacy have not been established in other nerve blocks.

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