Medication Assisted Treatment For Opioid Use Disorders - PowerPoint Presentation

Medication Assisted Treatment For Opioid Use Disorders Shannon Allen, MDJade Wellness CenterJuly 19, 2018

Rates of Relapse in Opioid Use Disorders are High

Benefits of Medication Assisted Treatments Reduce risk of overdose and death Improve social functioning Reduce risk of infectious disease transmission Reduce engagement in criminal activities Improved maternal and fetal outcomes Increased retention in treatment Safe

MAT Formulation Receptor Pharmacology FDA Approval in Pregnancy DEA Schedule Treatment Setting Naltrexone PO tablet Long acting intramuscular injection Implant (not FDA approved) Full mu opioid antagonist Not FDA approved, Not standard of care Non-narcotic Not scheduled Physician’s office, Opioid Treatment program, other health care setting

PO Naltrexone: Revia Range 25 mg – 150 mg /dayFDA recommends 50 mg /dayIM Naltrexone: Vivitrol -380 mg dose, Q4weeks -IM in the buttocks -Compliance is a huge barrier to treatment success

Benefits of Naltrexone Reduces cravingsPrevents effects of opiatesReduces rates of relapse to opiatesAny physician can prescribe No physiologic dependence Promoted by abstinence based models of treatment

Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson Jr, R. A., … & Gordon, M. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232-1242. Improved Opioid Outcomes with XR-NTX: Lower relapse rates Greater percentage of opioid-negative UDS Longer time to relapse Zero overdoses

Adverse Side Effects of Naltrexone Nausea, Vomiting Headache Appetite decreased Insomnia Dizziness Diarrhea Arthralgias Anxiety Depression, suicidal thoughts CPK increased Black Box warning for hepatoxicity Monitor LFTs Contraindicated in acute liver disease Decreased risk with Vivitrol

Injection Site Reaction with Vivitrol Increased risk if injection occurs in SC adipose layerRedness, induration, swelling, tenderness Can lead to cellulitis, abscess, necrosis

Precipitated Opioid Withdrawal with Naltrexone Recommendation is to be opioid free for minimum 7-10 daysNaloxone ChallengeCan be a barrier to starting antagonist treatment

Risk of Opioid Overdose with Naltrexone Accidental overdoses occur:After detox from opioids, before first dose is administeredWith attempts to overcome the opioid receptor blockadeUsing opioids after discontinuation of treatment Using opioids after missing a dose

Barriers to Naltrexone Lack of insurance or finances to pay for itPatient lack of awareness Physician lack of knowledgeIncarceration Complexity of ordering XR-NTX Complexity of administering

MAT Formulation Receptor Pharmacology FDA Approval in pregnancy DEA Schedule Treatment Setting Methadone Oral soln, liquid concentrate, table or diskette, powder Full mu opioid agonist Never formally approved by FDA, Gold standard II Opioid Treatment Programs

Historical Context of Methadone Maintenance Dr. Vincent Dole, becomes chair of Narcotics Committee of the Health Research Council of NYC. Joins with Dr. Marie Nyswander, an addiction psychiatrist, and together develop methadone as a maintenance therapy in 1964 “Methadone maintenance provides a safe and effective way to normalize the function of otherwise intractable opiate addiction” 1973 – Methadone Control Act Establishes federally funded clinics for prevention and treatment of opioid dependence. Regulates licensing for dispensing methadone.

Methadone Pharmacology Extensive bioavailabilityUp to 80% orally bioavailable Long elimination half life, ranging from 22-36 hours Allows for daily dosing Peak serum levels in 2-4 hours Highest rates of sedation, euphoria, analgesia Tolerance remains stable No need to escalate the dose (vs. short acting opioids) Hepatic metabolism through CYP450 enzymes Major substrate of CYP3A4 isozyme

Opioid Treatment Programs SAMHSA-certified program, that engages in supervised assessment and treatment for individuals who are addicted to opioids. Can include IOP, residential programs, hospital settings Variety of on-site services medically supervised withdrawal maintenance treatment medical, psychiatric, psychosocial and other types of supportive care. High level of regulations (federal, state, county, etc.)

Eligibility For Methadone Maintenance Must be 18 years old some states make exception for 16-18 yo Must have at least 12 months of physiologic dependence to opioids Exceptions: pregnancy Exceptions: high risk populations such as HIV positive, recently released from incarceration Must meet requirements for moderate to severe Opioid use disorder

Methadone Maintenance Goals Of Treatmentrelieve narcotic craving suppress the abstinence syndrome block the euphoric effects associated with opiates Minimize side effect profile Dosing Doses > 60 mg per day are recommended Most people stabilize between 60 – 120 mg daily

Methadone Side Effects Constipation, GI upset Excessive sweating Drowsiness, fatigue Decreased libido, hypogonadism QTc prolongation (and TdP) Increased risk with high dose methadone (>100 mg) Respiratory depression Central sleep apnea Death – usually due to respiratory arrest (esp with BZD, EtOH) or fatal arrhythmia

Barriers to Methadone Maintenance Treatment Lack of insurance or finances to pay for treatmentIncarceration Only 55% of prison systems allow for prescription of methadone Logistics of frequent dosing Transportation, childcare, time off from work, etc Legal involvement Must meet state eligibility

MAT Formulation Receptor Pharmacology FDA Approval in Pregnancy DEA Schedule Treatment Setting Buprenorphine Sublingual tablet or film *mono-product *combination- product with Naloxone Subdermal implant Subcutaneous injection Partial mu opioid agonist Not FDA approved III Physician’s office, Opioid Treatment program, other health care setting

History of Buprenorphine Maintenance Drug and Alcohol Treatment Act (DATA) 2000Schedule III, IV, V medications can be prescribed as maintenance treatment for opioid dependence qualifying physicians  can receive a  waiver  from the special registration requirements in the Controlled Substances Act Can be office based (vs. OTP) In 2002, FDA approves buprenorphine as a schedule III medication for treatment of opioid dependence

Buprenorphine Properties High Receptor Affinity Can precipitate withdrawalSlow Dissociation (long ½ life) Elimination half life is 20-73 hrs (mean 37 hrs) Low Intrinsic activity (partial agonism)

Buprenorphine Pharmacology Partial agonist at mu opioid receptor Low intrinsic activity Creates ceiling effect Reduced side effect profile Reduced risk for respiratory depression and overdose

Buprenorphine Induction Patients are advised to abstain from short-acting opiates for >24 hours, long acting opiates for >48-72 hoursGoal: Moderate Withdrawal COWS >10 CINA >10 Buprenorphine is initiated at low dose 2-4 mg If no precipitated withdrawal within 2 hours, can repeat dose (up to 8 mg on day 1)

Buprenorphine Formulations Poor oral bioavailability<40% of SL administration 2 sublingual formulations Buprenorphine (Subutex) Preferred formulation in pregnancy and breastfeeding Buprenorphine with naloxone (Suboxone, Zubsolv) 4:1 buprenorphine to naloxone Naloxone, only active if IV or IM administration Added to limit diversion

Buprenorphine Formulations Buccal formulation (Bunavail)-- daily--4:1 buprenorphine to naloxone

Buprenorphine Formulations Subdermal implant (Probuphine)--buprenorphine mono-product--8 mg equivalent--Remove and reinsert at 6 months --Must complete training to prescribe and surgically insert/remove

Buprenorphine Formulations Subcutaneous injection (Sublocade)--Buprenorphine mono-product--Repeat injections every 4 weeks 2 x 300 mg, then 100 mg maintenance dose --corresponds to 100% mu receptor occupancy --Must be REMS certified --Blackbox warning: intravenous administration can result in potentially fatal thrombo-embolic events

Buprenorphine Dosing (sublingual) Dosing range from 2-32 mg SL dailyFDA does not support doses above 24 mg Typically therapeutic dose is 16 mg SL daily 95% receptor occupancy at 16 mg (Greenwald et al. 2003) Some managed care will not cover more than 16 mg, or more than 1 year of treatment

Buprenorphine Side Effects Constipation, GI upset Excessive sweating Drowsiness, fatigue Decreased libido, hypogonadism QTc prolongation?? Central sleep apnea Respiratory Depression (especially with BZD) Children are vulnerable

Diversion of Buprenorphine is Uncommon In 2014, Buprenorphine made up <1% of all reported drugs diverted in the United StatesReasons: To manage withdrawal To self treat pain To self treat depression

Barriers to Buprenorphine Maintenance Lack of insurance or finances to pay for treatmentFear of legal consequences Incarceration Only 14% of prison systems allow for prescription of buprenorphine Not enough certified or trained prescribers Patient limits Of all physicians with waivers, <½ are not treating patients Lack of support services Difficult, time consuming Fear of audits

MAT Barriers: Insurance Coverage Initial and Reauthorization RequirementsLimits on dosagesLimits on quantity“Fail First” criteria Annual or lifetime medication limits Refusal to cover specific MAT

MAT Barriers: Provider Inadequate TrainingTreatment of addiction is limited in medical school and residenciesTherapists are not trained about MAT Negative attitude, Stigma Follow Abstinence Base Philosophy Suboptimal Dosing Preference for detox or tapering off

MAT Barriers: Pharmacy Refusal to carry MATNegative attitudes, StigmaAdditional RequirementsRefusal to fill prescriptions

MAT Barriers: Patients Stigma, negative attitudeConfidentiality concernsInconvenientLack of information Fear of legal consequences

Which MAT Should I Choose?

Treatment Works! But no single treatment is right for everyone