Buprenorphine for Family Medicine. Hannah Snyder, MD Addiction Medicine Fellow, UCSF 12/7/17

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+ Buprenorphine for Family Medicine Hannah Snyder, MD Addiction Medicine Fellow, UCSF 12/7/17

+ Disclosures No conflicts of interest Off-label use of medications

+ Who here: Has taken care of a patient on buprenorphine? Has an X License? Has primary care patients on buprenorphine?

+ Key Points Addiction is a chronic brain disease Opioid agonist treatment works Opioid agonist maintenance works better Buprenorphine and methadone both work it depends on the patient Prescribing in primary care is easy and important

+ Addiction is a chronic illness Addiction is a chronic illness 40-60% of people relapse within a year of treatment Similar rates of symptom recurrence to other illness Medication is treatment NIDA, McClellan et al

+ Opioid Agonist Therapy (OAT) 6 Buprenorphine and methadone Goals: no withdrawal, cravings, sedation, no euphoria if use opioids Maintenance, not detox 8-9/10 relapse within 30 d Chutuape et al, 2017

+ Opioid Agonist Therapy (OAT) 7 Buprenorphine and methadone Goals: no withdrawal, cravings, sedation, no euphoria if use opioids Maintenance, not detox 40 35 30 25 20 15 10 5 All cause mortality per 1000 person years 0 In methadone Out of methadone In buprenorphine Out of buprenorphine Sordo et al 2017

+ Opioid Agonist Treatment Offer if meet OUD criteria Presenting with: Withdrawal Abscess, cellulitis, endocarditis Totally unrelated Part of any primary care practice, hospital One of most impactful interventions

+ Opioid agonist therapy prevents morbidity and promotes recovery 9 Reduce injection and illicit drug use Promotes return to work and family obligations Reduce HIV and HCV transmission Reduce bacterial infections Reduce criminal behavior

Opioid Y Opioid receptor

Y Non MAT Opioids: full agonist heroin, oxycodone, Percocet, etc Y Methadone: full agonist Activates receptor, prevents binding Y Buprenorphine: partial agonist High affinity, ceiling effect Y Naltrexone, naloxone: Full antagonist, high affinity

+ Naltrexone Opiate antagonist PO daily or IM monthly Not first line 28% not induced vs 6% for bup Lee et al 2017

+ Buprenorphine: a note about withdrawal Must be in withdrawal prior to induction Bup: high affinity, low intrinsic activity Risk of precipitated withdrawal Heroin Y Buprenorphine Y

+ Withdrawal Tachycardia Dilated pupils Goosebumps Yawning Runny nose, tearing Anxiety Pain Vomiting, diarrhea

Methadone Buprenorphine

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist, often paired with antagonist (naloxone) abuse deterrent

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid in OTP For pain: tablet Sublingual tablet/film For pain: patch, buccal, implant, IV

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions Allergy Severe liver disease QTc prolongation Drug-drug interactions High risk job Allergy Severe liver disease Heavy EtOH or benzo Need for opioids Recent methadone SAMHSA

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film QTc prolongation Cautions Drug-drug interactions Hypogonadism Risks Torsades Constipation Sweating Severe liver disease Heavy EtOH or benzo Precipitated withdrawal GI upset, constipation Headache Insomnia

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions QTc prolongation Drug-drug interactions Risks ++ + Sedation More dose-dependent sedation Severe liver disease Heavy EtOH or benzo Less sedation, ceiling effect SAMHSA

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions QTc prolongation Drug-drug interactions Risks ++ + Sedation + - Visit Frequency Daily may earn takehomes Severe liver disease Heavy EtOH or benzo Daily or weekly monthly SAMHSA

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions QTc prolongation Drug-drug interactions Risks ++ + Sedation + - Visit Frequency Daily Monthly Location of care OTP (aka methadone clinic) Severe liver disease Heavy EtOH or benzo Clinic w/ X waivered provider (primary care, prenatal, psychiatry, or addiction) SAMHSA

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions QTc prolongation Drug-drug interactions Risks ++ + Sedation + - Visit Frequency Daily Monthly Location of care OTP Clinic Severe liver disease Heavy EtOH or benzo Retention Higher Lower (RR 0.89, CI 0.72-0.95), unless 16 mg SAMHSA, Cochrane

Methadone Buprenorphine Mechanism Full opioid agonist Partial agonist Formulation Liquid Sublingual tablet/film Cautions QTc prolongation Drug-drug interactions Risks ++ + Sedation + - Visit Frequency Daily Monthly Location of care OTP Clinic Retention Higher Lower Opioid negative urine Equivalent Severe liver disease Heavy EtOH or benzo Equivalent at doses 16 mg SAMHSA, Cochrane

+ Pregnancy Either buprenorphine or methadone MOTHER study: buprenorphine vs methadone Shorter hospitalization, less morphine w buprenorphine Buprenorphine without naloxone (for now) Jones et al

+ Buprenorphine: Misconceptions Diversion Sedation Can t control pain acute and chronic Substituting one drug Contraindicated w EtOH or benzos Induction in clinic only

+ Buprenorphine: Implementation Legal: X waiver (incl NP & PA) Max 30 patients Log all prescriptions for DEA Monitoring: PDMP/CURES Utox, urine buprenorphine LFTs if elevated Prescribing: Phone in/manual fax/paper rx Any pharmacy under MediCal Carve Out Behavioral: consider counseling, 12 step

+ Don t forget Other substance use Safe injection HIV, hepatitis Mental health Naloxone, PREP

+ Key Points Addiction is a chronic brain disease Opioid agonist treatment works Opioid agonist maintenance works better Buprenorphine and methadone both work it depends on the patient Prescribing in primary care is easy and important

+ What next? X License trainings https://tinyurl.com/asamwaiver https://tinyurl.com/pcssmatwaiver Substance Use Warmline http://nccc.ucsf.edu/clinical-resources/substance-use-resources/ (855) 300-3595 Monday Friday, 9 a.m. 8 p.m. EST Hannah.Snyder@ucsf.edu

+ References https://www.asam.org/docs/default-source/advocacy/opioid-addiction-disease-facts-figures.pdf Chutuape, M et al. One-, three-, and six-month outcomes after brief inpatient opioid detoxification. The American Journal of Drug and Alcohol Abuse. Vol 27:1, 2001. https://www.drugabuse.gov/publications/drugs-brains-behavior-science-addiction/treatment-recovery https://www.drugabuse.gov/sites/default/files/sanfrancisco2014.pdf Jones H, Kaltenbach K, Heil S, Stine S, Coyle M, Arria A, O Grady K, Selby P, Martin P, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. New England Journal of Medicine 2010; 363:2320-2331 Lee J et al. Comparative Effectiveness of extended release naltrexone vs buprenophrine-naloxone for opioid relapse prevention (X-BOT): a multicenter, open-label, randomized control trial. The Lancet 2017 Ling W, Hillhouse M, Domier C, Doraimani G, Hunter J, Thomas C, Jenkins J, Hasson A, Annon J, Saxon A, Selzer J, Boverman J, Bilangi R. Buprenorphine tapering schedule and illicit use. Addiction 2009; 104(2):256-265 McLellan A, Lewis D, O Brien C, Kleber H. Drug dependence, a chronic medical illness: Implications for treatment, insurance, and outcomes evaluation. JAMA 2000;284(13):1689-1695 Mattick R, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014. Mattick R, Breen C, Kimber J, Davoli M. Methadone Maintenance Therapy vs no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews 2009. www.naabt.org https://www.nytimes.com/interactive/2017/06/05/upshot/opioid-epidemic-drug-overdose-deaths-are-risingfaster-than-ever.html Ries R, Fiellin D, Miller S, Saitz R. The ASAM Priniciples of Addiction Medicine, 5 th Edition. 2014. Wolters Kluwer. SAMHSA NSUDH: https://www.samhsa.gov/data/sites/default/files/nsduh-ffr1-2016/nsduh-ffr1-2016.pdf SAMHSA MAT-PDOA. Providing Pharmacotherapy for Pregnant and Postpartum Women With Opioid Use Disorder: A Guide. https://www.samhsa.gov/medication-assisted-treatment/training-resources/buprenorphine-physician-training Sordo L, Barrio G, Bravo M, Indave B, Degenhardt L, Wiessig L, Ferri M, Pastor-Barriuso R. Mortality Risks During and After Opioid Substitution Treatment: Systematic Review and Meta-Analysis of Cohort Studies. BMJ 2017; 357:j1550. Zador D, Sunjic S. Deaths in methadone maintenance treatment in New South Wales, Australia 1990-1995, Addiction 2000; 95(1):77-84