Download set a smooth recovery in motion

USED
IN
MORE THAN
1
MILLION
PAT I E N T S
SET A SMOOTH RECOVERY IN MOTION
Reduce the need for opioids while providing long-lasting postsurgical
pain control…all from a single dose
Please refer to accompanying full Prescribing Information.
1
Opioid burden
Postsurgical pain management: an important part of recovery
Current treatment strategy leaves room for improvement
Although as many as 99% of postsurgical patients receive an opioid 2
74
%
of patients reported
moderate to extreme
pain after discharge3
57
%
of patients preferred
a nonopioid3
30
%
of patients
worried about
becoming addicted3
Source: Postsurgical patient survey of patients who had undergone surgery in the past 5 years (N=300).3
Opioids: effective, yet pose concerns for patients and health care providers 2,4-6
•A
dverse events increase risk of morbidity, delay ambulation, can increase length of stay, and may lead to hospital readmissions2,5
—O
pioids are not recommended in several high-risk patient populations4
—O
pioid-related issues can have a negative impact on patient satisfaction and reimbursement3,5,6
A high potential for misuse, dependency, or diversion creates a societal burden 7-9
• 1 in 15 patients prescribed opioids will go on to long-term use or abuse7,8
• In a study (N=250), the average patient consumed 1/3 of their opioid prescription, resulting in 4,639 leftover pills that could be diverted9
• In 2010, approximately 5 million people were classified as opioid abusers10
2
A multimodal strategy is recommended to reduce opioid reliance11-13
• American Society of Anesthesiologists (2012): Guideline Recommendations for Acute
Pain Management
“
”
Whenever possible, anesthesiologists should use multimodal pain management therapy.
11
• The Centers for Disease Control and Prevention and The Joint Commission
support an opioid-reducing strategy12,13
should reflect a [patient]-centered approach and consider the patient’s current
“Strategies
presentation, the health care providers’ clinical judgment, and the risks and benefits associated
with the strategies, including potential risk of dependency, addiction, and abuse.
”
12
The challenges of implementing an opioid-reducing strategy
• T he short duration of most local anesthetics (≤8 hours) limits their effectiveness when
postsurgical pain is at its worst 5,14
•S
upplementation is often needed with catheters and pumps, which can15-20
— Limit mobility
— Introduce risk of infection
— Cause variable infusion rates and concentrations
— Migrate or dislodge
• T he average cost of catheter and pump maintenance, monitoring, and materials
adds up to >$60020,21
3
DepoFoam®
Cutting-edge technology sets EXPAREL apart
With a unique drug delivery system, EXPAREL is designed to extend postsurgical analgesia
• Indicated for single-dose administration into the surgical site to produce postsurgical analgesia
•D
epoFoam uniquely delivers bupivacaine over time to extend pharmacologic effect
— Encapsulates bupivacaine via a multivesicular liposomal drug
delivery technology22
— R
eleases bupivacaine over time as lipid membranes reorganize22
Plasma levels of bupivacaine may persist for 96 hours23,*
300
Plasma bupivacaine concentration (ng/mL)
Reliable release of a low dose of bupivacaine
over time1
• L onger duration provides coverage when postsurgical pain
250
*Data from TKA study.
200
is at its worst
150
• E liminates the need for titration with a single dose
100
• E liminates the need for external devices to prolong analgesia
• E XPAREL dosing is not weight based
50
— Different formulations of bupivacaine are not bioequivalent
0
even if the milligram dosage is the same; therefore, it is not
24
48
0
possible to convert dosing from any other formulation of
Time (h)
bupivacaine to EXPAREL and vice versa
•O
ther formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL
4
EXPAREL 266 mg
72
96
Pharmacokinetics
Low systemic exposure
to bupivacaine
EXPAREL Cmax values fell below adverse event thresholds
in clinical trials
EXPAREL Cmax (ng/mL)
4,500
Cardiac threshold
4,000
Cmax (ng/mL)
3,500
3,000
2,500
CNS threshold
2,000
1,500
1,000
500
0
Bony model
(Bunionectomy; 106 mg)
n=26
Soft-tissue model
(Hemorrhoidectomy; 266 mg)
n=25
• T he blood plasma level where CNS effects are typically seen with traditional bupivacaine: >2,000 ng/mL
• T he blood plasma level where cardiac effects are typically seen with traditional bupivacaine: >4,000 ng/mL
• T he rate of systemic absorption of bupivacaine is dependent on the total dose, the route of
administration, and the vascularity of the administration site
Please refer to accompanying full Prescribing Information.
5
Set a smooth recovery in motion with EXPAREL
EXPAREL: significant long-lasting pain control that reduces the
need for opioids
1,5
Cumulative reductions in pain and opioid use through 72 hours1,5
0
Percentage reduction
compared with placebo
N=189
10
20
30%
30
40
50
Reduction in
cumulative
pain scores
P<0.0001
45%
Reduction in
opioid
consumption
P=0.0006
•S
ignificant reductions in pain intensity up to 24 hours (P<0.0001) with a
45% decrease in opioid consumption through 72 hours; the clinical benefit
of the decrease in opioid consumption was not demonstrated1
6
Studies demonstrating the safety and efficacy of EXPAREL were conducted in hemorrhoidectomy and bunionectomy.
Set a smooth recovery in motion with EXPAREL
Significantly longer time to first
opioid rescue
5
Median time to first opioid use5
EXPAREL
Placebo
N=189
P<0.0001
14.3 hours
1.2 hours
0
2
4
6
8
10
12
14
16
Time (h)
• 2 8% of patients were opioid free at 72 hours with EXPAREL vs 10% with placebo (P<0.0008)5
Soft-tissue (hemorrhoidectomy) trial design1,5
•P
hase 3 trial of patients undergoing a 2- or 3-column excisional hemorrhoidectomy (N=189) randomized to receive single
administration of 266 mg of EXPAREL or placebo for postsurgical analgesia
•P
rimary endpoint was cumulative pain scores as reflected in the AUC of NRS through 72 hours
•P
lacebo was preservative-free saline for injection
•O
pioid rescue medication (up to 10 mg IM morphine) was available to all patients
Please refer to accompanying full Prescribing Information.
7
Set a smooth recovery in motion with EXPAREL
Assessing the full value of EXPAREL:
pain reduction + opioid reduction
Significantly lower AUC NRS scores vs placebo1,24
AUC NRS scores
6
5
EXPAREL
Placebo
P<0.0001
N=189
P<0.0001
4
P<0.0001
3
P=0.0007
P=0.0388
2
P=0.1361
P=0.5371
24
36
P=0.5289
P=0.9094
P=0.8383
48
60
72
1
0
1
2
4
8
12
Time (h)
• 0 -24 hours: EXPAREL demonstrated significant reductions in pain intensity scores vs placebo24
Significantly less cumulative opioid consumption vs placebo1,24
Opioid consumption (mg)
20
16
EXPAREL
Placebo
N=189
P<0.0001
12
P=0.0003
48
60
P=0.0006
P<0.0001
P<0.0001
8
4
0
12
24
36
Time (h)
8
P<0.0001
72
contrast to looking at pain
“Inscores
alone, the use of multiple
outcome measures [including
the use of postsurgical opioid
rescue medication] may provide
a more meaningful assessment
of the therapeutic effects of
an analgesic medication in a
clinical study setting. 24
”
—Schmidt
Set a smooth recovery in motion with EXPAREL
EXPAREL: meeting the need for lasting
efficacy while reducing opioid reliance
0-24 hours: EXPAREL demonstrated a
significant reduction in pain intensity scores
•D
ifferences in scores diminished over time due to use of rescue medication24
• In the placebo group, median time to first rescue medication was 1.2 hours;
use of rescue medication led to equalization in pain control beginning at 24 hours1,24
— Rescue medication (up to 10 mg IM morphine) was available every 4 hours as needed over the first 72 hours
— By 24 hours postsurgery, 88% of placebo patients had used opioid rescue medication
Cumulative difference in opioid consumption
was maintained through 72 hours
•R
eduction in cumulative pain intensity scores was maintained with
less cumulative opioid use through 72 hours24
Please refer to accompanying full Prescribing Information.
9
Set a smooth recovery in motion with EXPAREL
EXPAREL: tolerability and safety profile similar to placebo
1
In clinical trials
•S
afety evaluated in 21 clinical trials (1,307 patients received EXPAREL)1
— 1 0 wound infiltration trials: 823 patients
—N
umerous procedures; EXPAREL doses ranged from 66 mg to 532 mg
•W
ell tolerated; most common adverse events (incidence ≥10%) were nausea, constipation, and vomiting
• E XPAREL demonstrated a favorable cardiac safety profile25,26
—N
o detectable cardiac toxicity signal
—N
o QTc prolongation, even at supratherapeutic doses
In clinical practice
• L ow incidences of adverse events (0.04%) reported in postmarketing integrated safety analysis following 600,000 exposures1
More than
1 million patients
have received EXPAREL
since 2012 1
10
Set a smooth recovery in motion with EXPAREL
A single dose of EXPAREL delivers
long-lasting pain control1
•D
ose EXPAREL based on the administration site and the volume required
to cover the area
— C
an be administered undiluted or expanded up to a total volume of
300 mL with normal (0.9%) saline for injection or lactated Ringer’s
solution to accommodate the size of the surgical site
•A
vailable as 266 mg, 1.3%/20 mL single-use vials
•M
aximum dose of EXPAREL should not exceed 266 mg (one 20 mL vial)
•N
o dosage adjustment needed for mild to moderate hepatic impairment, renal impairment, or elderly patients
Important Safety Information
Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL
as with other local anesthetic products.
Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in
patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally,
are at a greater risk of developing toxic plasma concentrations.
Please refer to accompanying full Prescribing Information.
11
Set a smooth recovery in motion with EXPAREL
EXPAREL administration
• Inject EXPAREL slowly into soft tissues of the surgical
site with frequent aspiration to check for blood and
minimize the risk of intravascular injection
Epidermis
1
2
3
4
Dermis
Nociceptors
Subcutaneous
tissue
Fascia
Muscle
Administration precautions
•W
ait 20 minutes after administering other non-bupivacaine-based local anesthetics before administering EXPAREL into the same
surgical site
•A
llow topical antiseptics to dry before administering EXPAREL into the same surgical site
•W
hen using bupivacaine HCl before EXPAREL, the dose of bupivacaine HCl should be ≤50% the dose of EXPAREL. As a reference:
— One 20 mL vial of EXPAREL contains 266 mg of free base bupivacaine; 266 mg of free base bupivacaine is equivalent to 300 mg of
bupivacaine HCl
— One 30 mL vial of 0.5% bupivacaine HCl contains 150 mg bupivacaine HCl
— Toxic effects of these drugs are additive and their administration should be used with caution, including monitoring for neurological
and cardiovascular effects
•D
o not admix EXPAREL with other drugs prior to administration
12
Set a smooth recovery in motion with EXPAREL
EXPAREL stays more precisely where placed,
requiring more injections to cover the same area
Technique and distribution are important when
administering into the surgical site
• Inject EXPAREL slowly into the soft tissue of the surgical site
Bupivacaine
EXPAREL
using a deep-tissue infiltration technique
—Administer EXPAREL with a 25-gauge or larger needle
• E XPAREL is best administered using a series of injections
to effectively cover the surgical area since it does not
diffuse throughout tissues in the same manner as
traditional bupivacaine
Note: Graphic is for illustrative purposes only.
Please refer to accompanying full Prescribing Information.
13
Important Safety Information
EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in
patients younger than 18 years of age.
Non-bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from
EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine
after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours
following administration of EXPAREL.
Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after
injection of EXPAREL as with other local anesthetic products.
Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be
used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability
to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.
In clinical trials, the most common adverse reactions (incidence ≥10%) following EXPAREL administration were
nausea, constipation, and vomiting.
Please refer to accompanying full Prescribing Information.
14
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References: 1. Data on file. Parsippany, NJ: Pacira Pharmaceuticals, Inc.; February 2015. 2. Kessler ER, Shah M, Gruschkus SK, Raju A. Cost and quality implications of opioid-based postsurgical pain
control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy. 2013;33(4):383-391. 3. Gan TJ,
Habib AS, Miller TE, White W. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. Published online: November 15, 2013.
Accessed March 4, 2015. 4. The Joint Commission. Safe use of opioids in hospitals. Sentinel Event Alert; August 8, 2012; Issue 49. 5. Gorfine SR, Onel E, Patou G, Krivokapic Z. Bupivacaine extendedrelease 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. 6. Survey of patients’ experiences. Medicare.gov website. http://www.medicare.gov/HospitalCompare/Data/PatientSurvey/Overview.aspx. Accessed January 5, 2015. 7. Alam A,
Gomes T, Zheng H, Mamdani MM, Juurlink DN, Bell CM. Long-term analgesic use after low-risk surgery: a retrospective cohort study. Arch Intern Med. 2012;172(5):425-430. 8. Carroll I, Barelka P,
Wang CK, Wang BM, et al. A pilot cohort study of the determinants of longitudinal opioid use after surgery. Anesth Analg. 2012;115(3):694-702. 9. Rodgers J, Cunningham K, Fitzgerald K, Finnerty E.
Opioid consumption following outpatient upper extremity surgery. J Hand Surg Am. 2012;37(4):645-650. 10. Popping pills: prescription drug abuse in America. National Institute on Drug Abuse website.
http://www.drugabuse.gov/related-topics/trends-statistics/infographics/popping-pills-prescription-drug-abuse-in-america. Accessed March 4, 2015. 11. 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. 2004;100(6):1573-1581. 12. The Joint Commission. Clarification of the Pain Management Standard PC.01.02.07. Joint Commission Perspectives. 2014;34(11):11.
http://www.jointcommission.org/assets/1/18/Clarification_of_the_Pain_Management__Standard.pdf. Accessed March 4, 2015. 13. Centers for Disease Control and Prevention. Common elements in
guidelines for prescribing opioids for chronic pain. http://www.cdc.gov/drugoverdose/prescribing/common-elements.html. Updated April 1, 2015. Accessed June 12, 2015. 14. Golf M, Daniels SE, Onel E.
A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011;28(9):776-788. 15. Ilfeld BM, Loland VJ,
Sandhu NS, Suresh PJ, Bishop MJ, Donohue MC. Continuous femoral nerve blocks: the impact of catheter tip location relative to the femoral nerve (anterior versus posterior) on quadriceps weakness
and cutaneous sensory block. Anesth Analg. 2012;115(3):721-727. 16. Kinder R, Hsiung R. Overview of peripheral nerve blocks. In: Chu LF, Fuller A, eds. Manual of Clinical Anesthesiology. Philadelphia,
PA: Lippincott Williams & Wilkins; 2011. https://www.inkling.com/read/manual-clinical-anesthesiology-chu-fuller-1st/chapter-34/overview-of-peripheral-nerve. Accessed October 7, 2014. 17. Process
for handling elastomeric pain relief balls (ON-Q PainBuster and others) requires safety improvements. Institute for Safe Medication Practices website. https://www.ismp.org/newsletters/acutecare/
articles/20090716.asp. Accessed June 3, 2015. 18. I-Flow ON-Q pump with ONDEMAND bolus button. US Food and Drug Administration website. http://www.fda.gov/MedicalDevices/Safety/
ListofRecalls/ucm317826.htm. Accessed January 5, 2015. 19. Continuous peripheral nerve blocks in outpatients. NYSORA–The New York School of Regional Anesthesia website. http://www.nysora.com/
regional-anesthesia/foundations-of-ra/3055-continuous-peripheral-nerve-blocks-in-outpatients.html. Accessed January 5, 2015. 20. Frost & Sullivan. New opportunities for hospitals to improve
economic efficiency and patient outcomes: the case of EXPAREL™, a long-acting, non-opioid local analgesic. http://www.frost.com/prod/servlet/cpo/252218999. Accessed January 5, 2015. 21. White PF,
Kehlet H, Neal JM, Schricker T, Carr DB, Carli F; Fast-Track Surgery Study Group. The role of the anesthesiologist in fast-track surgery: from multimodal analgesia to perioperative medical care.
Anesth Analg. 2007;104(6):1380-1396. 22. How DepoFoam® works. Pacira Pharmaceuticals, Inc. website. http://www.pacira.com/depofoam-platform/how-it-works.php. Accessed January 8, 2015.
23. Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to
bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012;19(5):530-536. 24. Schmidt WK, Patou G, Joshi GP. Evaluating therapeutic benefit in postsurgical analgesia requires
global assessment: an example from liposome bupivacaine in hemorrhoidectomy. Hosp Pract (1995). 2012;40(1):160-165. 25. Bergese SD, Onel E, Morren M, Morganroth J. Bupivacaine extended-release
liposome injection exhibits a favorable cardiac safety profile. Reg Anesth Pain Med. 2012;37(2):145-151. 26. Naseem A, Harada T, Wang D, et al. Bupivacaine extended release liposome injection does
not prolong QTc interval in a thorough QT/QTc study in healthy volunteers. J Clin Pharmacol. 2012;52(9):1441-1447.
15
In the management of postsurgical pain
A smooth start to recovery
begins with EXPAREL
Reduce the need for opioids while providing
long-lasting postsurgical pain control…
all from a single dose
• Indicated for single-dose administration into the surgical site
to produce postsurgical analgesia
•D
epoFoam® drug delivery system slowly delivers bupivacaine
over time to extend the pharmacologic effect of EXPAREL22
•S
ignificantly reduces opioid consumption1,5
• E liminates the need for catheters and pumps that may hinder recovery 2,5,15-20
• Safety and tolerability profile similar to placebo1
Used in more than
1 million patients
Please refer to accompanying full Prescribing Information.
For complete information related to EXPAREL, call 1-855-RX-EXPAREL (793-9727)
or visit www.EXPAREL.com.
©2015 Pacira Pharmaceuticals, Inc.
Parsippany, NJ 07054
PP-EX-US-0665
06/15
since 2012 1