Managing Pain in the Midst of an Opioid Epidemic

Transcription

1 Managing Pain in the Midst of an Opioid Epidemic Dr. Jim Silliman President, CEO GeneAlign Dr. Jerry L. Epps Chief Medical Officer University of Tennessee Medical Center

2 Disclosures The faculty members have a consulting relationship with Pacira Pharmaceuticals, Inc. This program is sponsored and approved by Pacira Pharmaceuticals, Inc. This program is not accredited for continuing education (CE), and attendees will not receive CE credit These presentations are reflective of the individual faculty members experience and are not intended as recommendations by Pacira Pharmaceuticals, Inc. 2

3 A Potential Gateway to Long-Term Opioid Addiction Current pain management strategies are overreliant on opioids as the premier source of pain management Table of Contents The University of Tennessee Medical Center Case Study Observing a potential target population and how it may benefit from a personalized pain management approach Taking Steps Toward Change Identifying the effort required to improve pain management

4 A Potential Gateway to Long-Term Opioid Addiction Current pain management strategies are overreliant on opioids as the premier source of pain management

5 The National Prescription Drug Epidemic White House Summit on the Opioid Epidemic 1 : The abuse of opioids has a devastating impact on public health and safety in this country CDC 2 : 46 people in the United States die from an overdose of prescription painkillers every day 259 million prescriptions were written for painkillers in 2012 by healthcare providers Enough for every American adult to have a bottle of narcotic pills 10 of the highest prescribing states for painkillers are in the South References: 1. President Barack Obama White House Archive website. Accessed March 8, Centers for Disease Control and Prevention website. Accessed March 8,

6 A Lost Middle Ground: Pain Management Has Evolved From Undertreatment to Overreliance and Overtreatment 1980s Published studies and letters posit that opioids do not carry significant risks for adverse events or addiction 1,2 Pain is established as a fifth vital sign. Consistent pain management guidelines that rely on opioids are created 3,4 Today, more Americans die because of drug overdoses than because of car crashes, and most of these overdoses involve some form of opioid 5 References: 1. Porter J et al. N Engl J Med. 1980;302(2): Portenoy RK et al. Pain. 1986;25(2): Pain as the 5th Vital Sign Toolkit. Washington, DC: Dept of Veterans Affairs; Federation of State Medical Boards of the United States, Inc. Advocacy/pain_policy_july2013.pdf. Accessed March 3, Murthy VH. Public Health Reports. 2016;131: US Surgeon General 6

7 Opioid-Related Adverse Events Are Commonplace THE SITUATION THE CURRENT STANDARD OF CARE THE OUTCOME 73 % 99 % 92 % of inpatient surgeries report moderate to extreme pain after surgery 1 of patients receive opioids to manage postsurgical pain 2 of postsurgical patients who receive opioids report some sort of adverse events 3 References: 1. Gan TJ et al. Curr Med Res Opin. 2014;30(1): Kessler ER et al. Pharmacotherapy. 2013;33(4): Gregorian RS et al. J Pain. 2010;11(11):

8 Opioids Provide Pain Management, but at What Cost? 1 in 15 patients who receive postsurgical opioids become addicted 1,2 References: 1. Alam A et al. Arch Intern Med. 2012;172(5): Carroll I et al. Anesth Analg. 2012;115(3):

9 Reliance on Opioids Places a Burden on Healthcare Resources Patients experiencing opioid-related adverse events have higher healthcare resource utilization and costs % 150% longer hospital stays 47% 86% higher costs 36% 68% higher readmission rates References: 1. Kessler ER et al. Pharmacotherapy. 2013;33(4): Oderda GM et al. J Pain Palliat Care Pharmacother. 2013;27(1): Minkowitz HS et al. Am J Health Syst Pharm. 2014;71(18): Gan TJ et al. Curr Med Res Opin. 2015;31(4):

10 The Operating Room Inadvertently Becomes a Point of Origin for Long-Term Opioid Addiction 10

11 Postsurgical Opioid Utilization Can Lead to Chronic Use Patients 1 year after surgery 1 Patient aged 65 years with an opioid prescription 7 days postsurgery 2 33% of all patients were still using opioids 18% of opioid-naïve patients were still using narcotics 10% remained on opioids 1 year later 44% increased chance of becoming a long-term opioid user The current hospital pain management strategy suggests a need for non-opioid solutions References: 1. Wang M et al. Spine J. 2013; 13(9):S6-S7. 2. Alam A et al. Arch Intern Med. 2012;172(5):

12 Common Surgeries Create a Surplus of Opioids That Flood the Market With Product Proportion of patients taking half or less of prescribed opioid pills 1 C-SECTION 83% 71% THORACIC SURGERY Outpatient upper extremity surgery 2 ~ 300 patients, with 92% reporting adequate pain control Usually received 30 narcotic pills >50% took pain pills for 2 days or less Consumed an average of 11 pills per patient Almost 5000 leftover tablets Initiation of short-term opioid therapy may lead to long-term use References: 1. Bartels K et al. PLoS ONE. 2016;11(1):e Rodgers J et al. J Hand Surg Am. 2012;37(4):

13 Reducing Misuse, Abuse, and Diversion Controlled prescription drugs (CPDs) are abused at a higher rate than any illicit drug except marijuana 1 Pain medications are: The most common CPDs used illegally Most often involved in incidents of overdose Diversion of CPDs costs insurers up to $72.5 billion per year 2 References: 1. Drug Enforcement Administration website. Accessed March 8, US Dept of Justice website. Accessed March 8,

14 The University of Tennessee Medical Center Case Study Observing a potential target population and how it may benefit from a personalized pain management approach

15 Tennessee Department of Health Controlled Substance Database The number of prescription drugs prescribed annually for every Tennessean older than 12 years 1 51 PILLS OF HYDROCODONE 21 PILLS OF OXYCODONE Reference: 1. East Tennessee State University website. Accessed March 8,

16 Deaths Comparison of Select Causes of Death Tennessee Resident Select Causes of Death, Assault Suicide Overdose Reference: 1. East Tennessee State University website. Accessed March 8,

17 Observing Opioid Misuse in Tennessee to Identify Specific Populations That May Benefit From an Individualized Approach 1 For every person who dies, there are 851 people in various stages of misuse, abuse, and treatment At least 1,074,813 Tennesseans (1 in 6) misuse or abuse opioids or are in treatment 12,630 in treatment admissions for abuse Those who died in ,838 emergency department visits for misuse or abuse 136,404 who abuse opioids or are dependent 925,779 non-medical users Reference: 1. The Tennessean website. Accessed March 8,

18 University of Tennessee Medical Center: Summary of Changes Pain scale Emphasis on function Pathways: Impact in Cerner For pain orders embedded in disease/procedural pathway for minimal change Guidance established for inexperienced clinicians via 2 new pain pathways Experienced clinicians (hospitalists) using general medicine pathways essentially unaffected Multimodal (non-narcotic options) easier to access in computerized physician order entry Pain flowsheet 3 Strikes you re out (evaluate) Guidance for expected responses for both nursing and physicians established Red flags Prompt to identify the accurate diagnosis and treat the cause of the pain Use of sedation scales Escalation of nursing or patient concerns Something s not right! Mandatory attending evaluation Morphine milligram equivalents Common language of how much On-site drug disposal receptacle Secure and Responsible Drug Disposal Act 2010 Standardized management of opioid misuse Patient compact Nursing aid Withdrawal Addiction treatment 18

19 The Revised Pain Scale The pain scale has been revised to incorporate patient functional abilities. This will help patients to score their pain more accurately with a reference point PAIN ASSESSMENT RULER 1-10 PAIN INTENSITY SCALE NO PAIN CAN BE IGNORED ANNOYING VERY DISTRACTING VERY INTENSE UNBEARABLE Activity normal Able to function Affects physical ability Limits normal activity Can only think about pain Unable to function or speak 19

20 Where We Are Going Enhanced recovery after surgery 1 Understanding Opioid risk Multimodal pain management 2 management 3 the effects of β-endorphins 4 Personalized medicine through pharmacogenetics Utilizes the analysis of the genes responsible for the metabolism of medications and determined inherited variations that can affect a patient s response to certain medications 5 References: 1. Melnyk M et al. Can Urol Assoc J. 2011;5(5): Boston University Medical Campus website. ALFORD-Chronic-Pain-and-Opioid-Risk-Management.pdf. Accessed March 3, Beck DE et al. Ochsner J. 2015;15(4): Sprouse-Blum AS et al. Hawaii Med J. 2010;69(3): GeneAlign website. Accessed March 8,

21 Using Pharmacogenetics to Personalize Medicine May Help Improve Pain Management Strategies Personalized (precision) medicine National Institutes of Health: Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in environment, lifestyle and genes for each person 1 Pharmacogenetics Testing for an individual s ability to respond and process medications based on DNA 2 Opioid use PATIENT S MEDICATIONS Hydrocodone (Vicodin ) Diphenhydramine (Benadryl ) (OTC) Clopidogrel (Plavix ) Omeprazole (Prilosec ) (OTC) St. John s Wort (OTC) TARGET METABOLIC ENZYMES CYP2D6 CYP2C19 CYP3A4 PROPOSED NEW MEDICATION Fluoxetine (Prozac ) Optimized medication selection may provide faster and more efficient symptom relief 3 Simvastatin (Zocor ) CYP, cytochrome P-450; DNA, deoxyribonucleic acid; OTC, over the counter. References: 1. National Institutes of Health website. Accessed March 8, Scott SA. Genet Med. 2011;13(12): GeneAlign website. Accessed March 22,

22 OBAS Score Pharmacogenetic Guidance in Analgesia Selection Reduces Opioid Consumption and Improves Pain Management A recent study demonstrated that using pharmacogenetic guidance can reduce opioid use by 50%, as well as incidences of analgesia-related side effects 1 Using genetic testing for pain management improved the OBAS rating for patients recovering from surgery To improve analgesia assessment, the OBAS rating takes into consideration distress from opioid symptoms, analgesia effectiveness, and patient satisfaction OBAS SCORE 1 Pharmacogenetic Group Historical Group 0 POD 1 POD 5 Days Postsurgery P=0.01 OBAS, overall benefit of analgesia score; POD, postoperative day. References: 1. Senagore AJ et al. Am J Surg. 2017;213(3): Lehmann N et al. Br J Anaesth. 2010;105(4):

23 Work Flow for Addiction Risk Assessment Report Addiction Risk Results Behavior SOAPP Version 1.0-SF Score 12 Toxicology Genetics BDNF OPRM1 DRD2 BDNF, brain-derived neurotrophic factor; DRD2, dopamine receptor D2; OPRM1, opioid receptor mu 1; SOAPP, Screener and Opioid Assessment for Patients with Pain. 23

24 Health Plan Beta Test GeneAlign Gene Extensive Metabolizer (Normal) Intermediate Metabolizer (Impaired) Poor Metabolizer (Elevated Risk) Ultra-Rapid Metabolizer (Elevated Risk) Total Impaired Population 2D6 43% 33% 25% NA 58% 2C19 40% 25% 4% 31% 60% 2C9 65% 31% 4% NA 35% 3A4 94% 6% NA NA 6% 3A5 56% 22% 22% NA 44% 24

25 Patients Respond Differently to Medications, Thus Requiring Personalized Treatment PHARMACOGENETIC TESTING SAME DIAGNOSIS DIFFERENT PRESCRIPTIONS Good responders to Drug A Good responders to Drug B Good responders to Drug C Treatment-resistant or refractory patients 25

26 Reduction in Metabolic Opioid Severity a 11% Safe 62% Safe 58% Caution Before 36% Caution After 31% Warning 2% Warning a Based on 43 patients on opioids with CYP2D6 impairment. 26

27 Opioid Reduction With Multimodal Analgesia in TKA Ketamine 1 10%-30% NSAIDs 2,3 ~15%-55% Gabapentinoids 4,5 10%-49% Dexamethasone 7 41% IV acetaminophen 6 Average reduction of 9 mg of morphine equivalents IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug; TKA, total knee arthroplasty. References: 1. Moodie JE et al. Anesth Analg. 2008;107(6): Kazerooni R et al. J Arthroplasty. 2012;27(6): Rawal N et al. BMC Musculoskelet Disord. 2013;14: Mathiesen O et al. Br J Anaesth. 2008;101(4): Buvanendran A et al. Anesth Analg. 2010;110(1): Apfel CC et al. Pain. 2013;154(5): Backes JR et al. J Arthroplasty. 2013;28(8 suppl):

28 Opioid Reduction With Multimodal Analgesia in TKA Drugs Dose Before Surgery Route of Administration Time Before Surgery PGx Guidance NSAIDs Ketorolac Ibuprofen mg 800 mg PO/IV PO 1-2 h 1-2 h Ultra-rapid metabolizer 1A2 COX-2 inhibitors Celecoxib 400 mg PO 1 h Normal metabolizer 2C9, 2D6 Antineuropathic Gabapentin Pregabalin 1200 mg 150 mg PO PO 1-2 h 1 h Normal metabolizer 3A4, 2D6 Propacetamol Acetaminophen 2 g 1 g PO/IV PO/IV 15 min 15 min NA Liposomal bupivacaine Up to 266 mg Injection into the soft tissues of the surgical site during surgery Normal metabolizer 3A4 Please see Important Safety Information on slides 35 and 36. Full Prescribing Information is available at COX, cyclooxygenase; NA, not applicable; PGx, pharmacogenetics; PO, by mouth. 28

29 Protocols for Personalized Pain Management Stratify preoperative patients based on addiction risk, PGx, DDI, and toxicology Track I Track II Track III CHARACTERISTICS Low genetic risk Negative addiction indication Negative toxicology screen PHARM D RECOMMENDATIONS Identify best available rescue narcotic based on patient's genetic profile Identify multimodal perioperative pain management RN-assisted transitioning to NSAIDs, ice, TENS, etc. NURSING OVERSIGHT Education related to opioid addiction CHARACTERISTICS Moderate genetic risk Negative addiction indication or mutated opioid genetics Negative toxicology screen PHARM D RECOMMENDATIONS Identify best available rescue narcotic based on patient's genetic profile Encourage multimodal perioperative pain management Limit exposure length to minimum RN-assisted transitioning to NSAIDs, ice, TENS, etc. NURSING OVERSIGHT Education related to opioid risk mutations and opioid avoidance CHARACTERISTICS High genetic risk Or positive addiction indication and mutated opioid genetics Or positive toxicology confirmation PHARM D RECOMMENDATIONS Perioperative narcotic avoidance Primary: multimodal perioperative pain management (EXPAREL [bupivacaine liposome injectable suspension] or other multimodal or long-lasting anesthetics) RN or MD telemedicine involvement in postoperative pain management ADDICTION SPECIALIST OVERSIGHT Education specific to narcotics Narcotic surveillance Please see Important Safety Information on slides 35 and 36. Full Prescribing Information is available at DDI, drug-drug interaction, TENS, transcutaneous electrical nerve stimulation. 29

30 Sample Processing and Reporting Cheek swab by healthcare professional Swab sent to the lab Lab inputs data into GeneAlign system Analyst simplifies data Pharmacist performs an in-depth analysis and provides perioperative management summary After testing, individual data is analyzed to establish the primary course of action in pain management throughout all steps of a patient s surgical procedure 30

31 Avoidance of Prescription Drug Abuse After Surgery: Protocol-Driven, Nursing-Directed Telemedicine Program Presurgical assessment of a patient s addiction risk SOAPP Version 1.0-SF Genetics panel Brain-derived neurotrophic factor Dopamine receptor D2 Opioid receptor mu 1 Positive/negative toxicology Presurgical and postsurgical pain-control counseling Pill dispensing Measured prescription amounts Unused medications returned Postsurgical pain-control monitoring 31

32 Taking Steps Toward Change Identifying the effort required to improve pain management

33 Potential Opportunity Provide a protocol-based personalized medicine program to identify patients at risk for prescription-drug abuse and to manage pain after discharge from the hospital Significantly reduce opioid use and addiction in the United States Reduce the cost of surgical care and pain management Decrease adverse drug events and deaths from overdoses Reduce the conversion to heroin and other illicit drugs Develop evidence-based national guidelines 33

34 Needs FUNDING Nursing Information technology Laboratory testing Counseling Data analytics SUPPORT Commercial and government payers Government and community leaders Physicians and other providers News and other media 34

35 EXPAREL (bupivacaine liposome injectable suspension) Important Safety Information EXPAREL is contraindicated in obstetrical paracervical block anesthesia In clinical trials, the most common adverse reactions (incidence 10%) following EXPAREL administration were nausea, constipation, and vomiting 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. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations Warnings and Precautions Specific to EXPAREL EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks, or intravascular or intra-articular use 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. Formulations of bupivacaine other than EXPAREL should not be administered within 96 hours following administration of EXPAREL Full Prescribing Information is available at 35

36 EXPAREL (bupivacaine liposome injectable suspension) Important Safety Information (cont d) 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 paresthesias. 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 Full Prescribing Information is available at 36

37 Thank you Dr. Epps: Dr. Silliman: All trademarks, registered or unregistered, are the property of their respective owners Pacira Pharmaceuticals, Inc. Parsippany, NJ PP-NP-US /17