Combating the Crisis: Medication Assisted Treatment DISCLOSURES DISCLAIMER 2/15/2019

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1 Combating the Crisis: Medication Assisted Treatment for Opioid Use Disorder Kiley Boeding, PharmD PGY I Pharmacy Resident Iowa City Veterans Affairs Healthcare System DISCLOSURES Dr. Boeding does not have any actual or potential conflicts of interest to disclose and will not be discussing off label use of medications. DISCLAIMER Methadone, buprenorphine, and naltrexone are all FDA approved options for opioid use disorder (OUD). This presentation will largely focus on methadone and buprenorphine as they are more commonly used in clinical practice. Non pharmacologic treatment options will not be mentioned during this presentation. As with any chronic disease, successful treatment involves a multifaceted approach. 1

2 GOAL Upon conclusion of this presentation, attendees will be able to identify the three FDA approved medication assisted treatment (MAT) options (methadone, buprenorphine, naltrexone) for opioid use disorder (OUD) and understand their place in therapy. PHARMACIST OBJECTIVES 1) Determine the role of MAT, such as methadone, buprenorphine, and naltrexone, in the treatment of opioid use disorder 2) Compare and contrast each MAT option, in terms of efficacy, tolerability, and accessibility, and be able to recommend appropriate therapy for a clinical scenario 3) Develop a dosing regimen for methadone and buprenorphine, including the induction and maintenance phase 4) Counsel a patient on the appropriate administration of MAT, such as buprenorphine/naloxone buccal or sublingual film 5) Describe potential barriers to MAT, and be able utilize various tools, such as the Iowa PMP Aware, to assist patients with finding potential MAT options PHARMACY TECHNICIAN OBJECTIVES 1) Determine the role of MAT, such as methadone, buprenorphine, and naltrexone, in the treatment of opioid use disorder 2) Distinguish between tolerance and withdrawal and be able to educate a patient or colleague on the difference 3) Characterize the different scheduled classifications of methadone, buprenorphine and naltrexone, and which requires a prescription from a provider with a DEA X waiver 4) Recall which medications used for opioid use disorder can be filled at a community pharmacy and which have to be prescribed and administered from a specialty clinic 5) Describe potential barriers to MAT, and be able utilize various tools, such as the Iowa PMP Aware, to assist patients with finding potential MAT options 2

3 ONE PERSON DIES FROM AN OPIOID RELATED DEATH EVERY 16 MINUTES CDC, Vital Signs, July 2017 Since 1999, overdose deaths from opioids, including prescription and illicit, have Increased six fold CDC, Understanding the Epidemic, December

4 MIDWESTERN REGION Opioid overdoses increased 70% from July 2016 to September 2017 CDC, Vital Signs, 2017 IOWA 2015: 59 opioid overdose deaths 163 opioid related deaths 2016: 86 opioid overdose deaths 180 opioid related deaths 2017*: 99 opioid overdose deaths 202 opioid related deaths *preliminary data Des Moines Register. February 2018 In 2016, 11.5 million people selfreported that they had personally misused prescriptions opioids during the previous year SAMHSA: Key Mental Health Indicators in United States: Results from the 2016 National Survey on Drug Use and Health. September

5 6% 53% drug dealer friend or relative or stranger 37.5% prescription or stealing from healthcare provider SAMHSA: Key Mental Health Indicators in United States: Results from the 2016 National Survey on Drug Use and Health. September 2017 Americans suffered from opioid use disorder in 2016 CDC. Assessing and Addressing OUD. October 2017 SAMHSA: Key Mental Health Indicators in United States: Results from the 2016 National Survey on Drug Use and Health. September 2017 Adults (26+) 89% 1.6 million Young Adults (18 25) 9% 392,000 Adolescents (12 17) 2% 153,000 CDC. Assessing and Addressing OUD. October 2017 SAMHSA: Key Mental Health Indicators in United States: Results from the 2016 National Survey on Drug Use and Health. September

6 PATIENT CASE: John Doe PATIENT CASE 29 year old male Auto mechanic Married; 1 st child due in July No history of medical or psychiatric conditions No medications Prescribed opioids following motor vehicle accident in 2014 Prescription pills progressed to heroin Approximately 25% of patients prescribed opioids for chronic pain misuse them Approximately 10% develop an opioid use disorder NIH, Opioid Overdose Crisis. January

7 Approximately 5% those who misuse opioids transition to heroin Approximately 80% of heroin users first misused prescription opioids NIH, Opioid Overdose Crisis. January 2019 Psychotropic substance use Psychological trauma Mental Health Diagnosis Dose Preadolescent sexual abuse Smoking Duration History of legal problems Substance Use Disorder History Nonfunctional status due to pain Poor Social Support Young Age Webster, L. Anesthesia & Analgesia: November 2017 Vol 125. Issue 5. pg PATIENT CASE Denies seeking prior help Medical, 12 step programs, etc. Multiple unsuccessful attempts on his own Endorsed daily heroin use Uses to avoid nausea, vomiting, diarrhea No longer talks to his parents Fired last week using on the job Afraid his wife will leave 7

8 DSM V DIAGNOSTIC CRITERIA FOR OPIOID USE DISORDER 1. Opioids are taken in larger amounts over a longer period than intended 2. Persistent desire or unsuccessful efforts to cut down or control opioid use 3. Great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects 4. Craving or a strong desire or urge to use opioids 5. Recurrent opioid use resulting in failure to fulfill major role obligations at work, school, or home 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems cause or exacerbated by the effects of opioids 7. Important social, occupation, or recreational activities are given up or reduced because of opioid use 8. Recurrent opioid use in situations in which it is physically hazardous 9. Continued opioid use despite knowledge of having persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance 10. Exhibits tolerance 11. Exhibits withdrawal American Psychiatric Association. DSM DSM IV DIAGNOSTIC CRITERIA FOR OPIOID USE DISORDER MILD MODERATE SEVERE Presence of 2 3 criteria Presence of 4 5 criteria Presence of 6 or more criteria Uncontrolled Use Multiple areas of life Tolerance or Withdrawal American Psychiatric Association. DSM TOLERANCE Need for markedly increased amounts of opioids to achieve intoxication or desired effect Markedly diminished effect with continued use of the same amount of opioids CDC. Assessing and Addressing OUD. October

9 DEPENDENCE A physical condition in which the body has adapted to the presence of a drug Suddenly stopping opioids results in predictable and measureable symptoms, known as withdrawal CDC. Assessing and Addressing OUD. October 2017 WITHDRAWAL Minutes to days of cessation/reduction Three or more of the following Dysphoric mood Nausea, vomiting, diarrhea Muscle aches Lacrimation or rhinorrhea Sweating Insomnia CDC. Assessing and Addressing OUD. October 2017 NORMAL EUPHORIA Medication Assisted Treatment WITHDRAWAL Tolerance & Physical Dependence ACUTE USE CHRONIC USE Weber, A. Reist, H. Opioid Use Disorders: Managing a Chronic Disease. Progress in Learning

10 GOALS OF MAT Suppress opioid withdrawal Decrease illicit opioid use Reduce cravings Reduce overdose death Promote and facilitate engagement in recovery orientated activities Produce a satisfying, productive life T.P.G Herbert D, et al. Am Psychiatr Assoc. no. August pp ROLE OF MAT Helps achieve longterm goal of reducing opioid use and the associated negative consequences, including death from overdose Retention in Treatment Employment Rates HIV/HCV Transmission Drug related criminal behavior Cravings Illicit drug use A VA Clinician s Guide to Identification and Management of Opioid Use Disorder Only 10% of patients with opioid use disorder receive treatment Bias against MAT Access to Care World Health Organization

11 BIAS AGAINST MAT Active disease is considered a criminal problem MAT is substituting one opioid for another Abstinence is more effective than MAT Not in my professional scope should be treated by an addiction specialist ACCESS TO CARE METHADONE SAMHSA certified outpatient therapy programs Daily onsite administration Potential for at home self administration One dose/week first 90 days Two doses/week second 90 days Up to 2 weeks of doses after 1 year Up to 1 month of doses after 2 years SAMHSA: Substance Abuse and Mental health Services Administration METHADONE CLINICS IOWA Sioux City Des Moines (x3) Cedar Falls Marion Cedar Rapids Davenport Knoxville Dubuque 11

12 METHADONE CLINICS IOWA CLINIC LOCATION BCBS MEDICAID CASH # United Community Services Cedar Valley Recovery Services Ankeny Des Moines Knoxville Cedar Falls Dubuque Marion Accepted * Accepted $10 per day Accepted * No^ $13 per day CRC Recovery Cedar Rapids No^ Accepted $12 per day Center for Behavioral Health Davenport Des Moines Sioux City No No $13 per day Covert Action Des Moines Accepted^ No $60 per week *Coverage varies depending on individual plan ^Pending acceptance #Cost of medication does not include potential admission fees, doctor or counselor fees ACCESS TO CARE BUPRENORPHINE Drug Addiction Treatment Act (DATA 2000) Treat opioid dependence from office based practice Schedule III V Physicians, nurse practioners, and physicians assistants with DEA X waiver Prescriber Patient Limits 30 patients per physician 100 patients per physician after 1 year 275 patients per physician after 2 years Any pharmacy can fill prescription for sublingual or buccal formulations 12

13 BUPRENORPHINE COST Medicaid Suboxone Buprenorphine/naloxone tablets (generic) Buprenorphine tablets (generic) Limitations Prior Authorizations Enrolled in treatment program Renewals require documentation of taper attempts source/advocacy/state medicaid reports/state medicaid reports_ia.pdf BUPRENORPHINE COST Blue Cross Blue Shield Buprenorphine sublingual tab (Tier 1) Buprenorphine/naloxone sublingual tab (Tier 1) Suboxone film (Tier 4) Subsolv sublingual tablets (Tier 4) Bunavail film (Tier 4) AWP Generic buprenorphine tablets = $ Suboxone films = $ source/advocacy/state medicaid reports/state medicaid reports_ia.pdf MEDICATION ASSISTED TREATMENT (MAT) METHADONE BUPRENORPHINE NALTREXONE 13

14 Opioid agonist therapy (OAT) should be considered 1 st line treatment for opioid use disorder VA/DoD, vol.version 3, no. December 2015, pp , METHADONE Full opioid agonist OPIOID BUPRENORPHINE Partial Agonist NALTREXONE Opioid Antagonist LOG DOSE NALTREXONE Opioid antagonist Decreased euphoria with opioid use Displaces other opioids Not a controlled substance Opioid free for 7 10 days prior Not recommended as first line agent A VA Clinician s Guide to Identification and Management of Opioid Use Disorder

15 METHADONE METHADONE First FDA approved opioid for detoxification and maintenance Schedule II controlled substance Full opioid agonist No ceiling effect METHADONE DOSING Induction Low dose (10 30mg/day) Daily monitoring Gradual titration over days to weeks Titration Adjust doses by 5mg or less every 5 days or more 5 10mg no sooner than every 3 4 days Maintenance Withdrawal symptoms prevented for 24 hours Reduced or eliminated cravings Blunts or blocks euphoria Usual dose (80 120mg/day) SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 Payte and Khuri Opioid Maintenance Pharmacotherapy A Course for Clinicians 15

16 PATIENT CASE After education and careful assessment, John is approved for methadone treatment. John arrives to clinic in withdrawal as instructed. You assist the provider with the induction and recommend 20mg. When should you assess response to therapy? a) 15 minutes b) 3 hours c) 6 hours d) Tomorrow METHADONE DOSING Remain in observation for 2 4 hours Symptoms lessen Intoxication or sedation Neither sedation nor reduction of withdrawal Administer another 5mg (wait 2 4 hours) Maximum total daily dose of 40mg SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 Payte and Khuri Opioid Maintenance Pharmacotherapy A Course for Clinicians METHADONE ADVERSE EFFECTS Amenorrhea Constipation Drowsiness Edema Nausea Respiratory depression Sexual dysfunction/decreased libido Sweating Weight gain 16

17 METHADONE PRECAUTIONS Respiratory depression QTc prolongation Drug Interactions Major: 2B6, 3A4 Minor: 2C19, 2C9, 2D6 METHADONE BASELINE MONITORING State PDMP History Physical exam Withdrawal Urine drug screen, blood alcohol Pregnancy test Hepatitis and HIV testing SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 METHADONE MONITORING Resolution of withdrawal symptoms Absence of euphoria (patient reported) ECG Constipation Nausea Pruritus Sedation SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February

18 METHADONE ADVANTAGES Reduces opioid cravings Blunts or blocks effects of other opioids Lower potential for euphoria 40+ years of research and treatment experience Improved treatment retention Drug Alcohol Depend. Vol 7, no 3, pp Jun 1981 Dole, E. McIntire, R. Dual Diagnosis: The Quandary of Chronic Pain, Chronic Opioids, MAT and Recover. ASHP Midyear 2018 METHADONE TREATMENT CONTROL (NO METHADONE) Decreased Drug Alcohol Depend. Vol 7, no 3, pp Jun 1981 A VA Clinician s Guide to Identification and Management of Opioid Use Disorder No drug abuse After 2 years, methadone recipients were more likely to be drug free and had fewer adverse outcomes No drug abuse Drug abuse In prison Deceased METHADONE DISADVANTAGES Abuse potential Full agonist, no ceiling effect Numerous drug interactions Access limited to methadone clinics Barriers to patient compliance Significant stigma in the community 18

19 METHADONE STIGMA Publicly funded buprenorphine outpatient treatment center in Baltimore, MD N= % African American; 33.8% female Mean age of 45.2 (SD=7.0) Structured Interview Why did you decide to get treatment with buprenorphine? What is the single most important reason that you entered buprenorphine treatment? Why did you choose buprenorphine and not methadone treatment? Gryczynski J, Jaffe JH, Schwartz RP, et al. Am J Addict. 2013; 22: METHADONE STIGMA Methadone was a drug substitution, limited therapeutic benefit Methadone was addicting, requiring longterm indefinite treatment; buprenorphine could be taking for a shorter duration Buprenorphine had less severe withdrawal Gryczynski J, Jaffe JH, Schwartz RP, et al. Am J Addict. 2013; 22: BUPRENORPHINE 19

20 BUPRENORPHINE Partial opioid agonist Ceiling effect High affinity for opioid receptors Single agent or combined agent with naloxone Combination to prevent diversion/injection Products are not interchangeable BUPRENORPHINE PREPARATIONS Single agent Belbuca (buccal film) Buprenorphine HCl (sublingual tablets) Buprenorphine + naloxone Suboxone (buccal or sublingual film) Bunavail (buccal film) Zubsolv (sublingual tablet) Buprenorphine/naloxone (sublingual tablet) BUPRENORPHINE PREPARATIONS Subcutaneous implant Probuphine Previously stabilized on buprenorphine 74.2mg buprenorphine released over 6 months Implanted by provider with special training Extended release injection Sublocade Monthly subcutaneous abdominal injection 20

21 BUPRENORPHINE DOSING Induction 2 4mg buprenorphine 2mg/0.5mg 4mg/1mg buprenorphine/naloxone Max: 8mg on day 1 Titration: 2 4mg increments Maintenance Target dose (16mg/day) Range 4 24mg SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 BUPRENORPHINE ADVERSE EFFECTS Constipation Glossodynia (tongue pain) Insomnia Nausea/Vomiting Oral hypoesthesia (oral numbness) Oral mucosal erythema Sweating BUPRENORPHINE PRECAUTIONS Respiratory depression Hepatic events Drug interactions Fewer drug interactions than methadone Metabolized by 3A4 Potential for diversion 21

22 BUPRENORPHINE BASELINE MONITORING State PDMP History Physical exam Withdrawal Urine drug screen, blood alcohol Pregnancy test Liver function test Hepatitis and HIV testing BUPRENORPHINE MONITORING Resolution of withdrawal symptoms Respiratory depression Blood pressure Constipation Liver function tests (baseline, periodically) BUPRENORPHINE ADVANTAGES Ceiling Effect Fewer drug interactions Naloxone combination IV abuse deterrent Take home dosing Less stigma 22

23 BUPRENORPHINE DISADVANTAGES Limited to providers with DEA X waiver Less pain control Lack of long term data Treatment retention is lower than methadone BUPRENORPHINE vs. METHADONE Multicenter, randomized, open label trial N=1269 Outcomes Treatment retention Methadone 74% vs. Buprenorphine 46% (p<0.01) Effect of dose on treatment retention High dose demonstrated better retention Methadone >60mg; 80% retention Buprenorphine 30 32mg; 60% retention Hser Y, et al. Addiction 2014 PATIENT CASE 6 months later, John comes back to your clinic after being stable on 100mg/day of methadone. With a new baby, he finds it difficult to get to the methadone clinic. He would like to switch to buprenorphine. What is your response? a) Recommend against changing therapy as patient is currently stable b) Calculate an equal analgesic dose and begin equivalent buprenorphine dose c) Abruptly stop methadone to induce withdrawal d) Taper methadone and induce withdrawal 23

24 METHADONE BUPRENORPHINE Taper methadone to 30mg/day Remain at that dose for 1 week Begin buprenorphine when the patient manifests symptoms of withdrawal 24+ hours between last methadone dose and first buprenorphine dose SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 Weber, A. Reist, H. Opioid Use Disorders: Managing a Chronic Disease. Progress in Learning 2018 PATIENT CASE 2 years later John is back in clinic. He is expecting their second daughter in a few weeks. He is wondering how long he will have to be on MAT? MAT LONG TERM THERAPY No known duration of treatment Longer durations = superior outcomes Goal of MAT Produce a satisfying, productive life NOT see how fast patients discontinue treatment SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February

25 MAT LONG TERM THERAPY Continue therapy as long as patients benefit and wish to continue No ideal tapering protocol Gradual taper (weeks to months) Individualized to patient response SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 MAT LONG TERM THERAPY Full Remission MAT maintenance Negative urine drug screens No other criteria for opioid use disorder Physically dependent, but not addicted SAMSHSA. TIP 63: Medications for Opioid Use Disorder. February 2018 METHADONE vs. BUPRENORPHINE Treatment Setting METHADONE Specialty licensed outpatient provider BUPRENORPHINE/ NALOXONE Office based Mechanism of Action Full agonist Partial agonist FDA approved for OUD Yes Yes Reduces Cravings Yes Yes Candidates with a history of failed treatment attempts Recommended for OUD candidates with pain conditions requiring shortacting opioids Many failed attempts Yes None/few failed attempts No A VA Clinician s Guide to Identification and Management of Opioid Use Disorder

26 PATIENT CASE John didn t show up to his appointment today. You call John and he states he fell on the ice and hurt his back. How do you treat acute pain in patients with OUD? PAIN MANAGEMENT AND OUD Risk vs. Benefit Identify the source Morning withdrawal symptoms may be misinterpreted as an exacerbation of pain Medications to avoid Opioid analgesics Sedative hypnotics Muscle relaxants Other medications with addiction potential A VA Clinician s Guide to Identification and Management of Opioid Use Disorder PAIN MANAGEMENT AND OUD Nonpharmacological therapies Assessment/treatment of co morbid psychiatric conditions Non opioid medications APAP, NSAID SNRI, TCA Topical (lidocaine, capsaicin) Gabapentin A VA Clinician s Guide to Identification and Management of Opioid Use Disorder

27 PAIN MANAGEMENT AND OUD Higher analgesic doses may be necessary Opioid analgesic tolerance Heightened pain sensitivity Divide opioid agonist therapy Duration of action shorter for analgesia Give dose more frequently (BID or TID) A VA Clinician s Guide to Identification and Management of Opioid Use Disorder PAIN MANAGEMENT AND OUD MEDICATION CONSIDERATIONS Non opioid therapies Smaller amounts of opioids and lowest effective dose MONITORING Frequent office visits Signs of relapse Early refills Unexpected UDS Dose increase requests TREATMENT PLANNING AND SUPPORT Manage co morbid psychiatric conditions Offer addiction treatment and support resources (12 step, counseling) Conduct pill counts Consult pain management specialist Opioid efficacy Frequent UDS and PDMP (2 4 times/year) Expand pain treatment to include relapseprevention strategies and directed relapse management A VA Clinician s Guide to Identification and Management of Opioid Use Disorder What if John Doe was Jane Doe? 27

28 OUD IN PREGNANCY Methadone and buprenorphine monotherapy are first line in pregnancy Improved prenatal care Reduced illicit drug use Minimizes risk of in utero fetal withdrawal Not recommended Naltrexone Detoxification American College of Obstetrics and Gynecologists.Obstet Gyencol 2012;119: CHANGE THE CONVERSATION Counter the stigma by using accurate, nonjudgmental language to describe OUD, those it affects, and its treatment with medications A VA Clinician s Guide to Identification and Management of Opioid Use Disorder USE PERSON FIRST LANGUAGE INSTEAD OF THIS Mr. Doe is an opioid addict Mr. Doe has a drug problem CONSIDER SAYING Mr. Doe has a substance use disorder involving opioids Mr. Doe is suffering from problems caused by drugs A VA Clinician s Guide to Identification and Management of Opioid Use Disorder

29 AVOID JUDGEMENTAL TERMINOLOGY INSTEAD OF THIS Your urine drug test was clean/dirty Mr. Doe uses narcotics You need to stop your habit of using opioids CONSIDER SAYING Your urine drug test was negative/positive for illicit substances Mr. Doe uses opioids Iwould like to help you get treatment for your opioid use disorder A VA Clinician s Guide to Identification and Management of Opioid Use Disorder BE SUPPORTIVE INSTEAD OF THIS There is no cure for your disease I can t help you if you choose to keep using opioids CONSIDER SAYING Recovery is achievable I understand that no one chooses to develop opioid use disorder. It is a medical disorder that can be managed with treatment A VA Clinician s Guide to Identification and Management of Opioid Use Disorder SUMMARY Methadone and buprenorphine are first line therapy for opioid use disorder Methadone has the best evidence for treatment but must be prescribed/administered within an approved treatment facility Higher doses of methadone and buprenorphine are associated with greater treatment retention Longer durations of therapy have superior outcomes; patients should continue MAT as long as they receive benefit and wish to continue 29

30 QUESTIONS? 30