Buprenorphine Induction and Maintenance Guidelines

Guidelines for buprenorphine induction and maintenance for patients dependent on short-acting or long-acting opioids. Covers microdosing, home vs. office induction, managing withdrawal symptoms, dose titration, patient education, and follow-up protocols. Includes information on assessing withdrawal, proper dosing, and transitioning from methadone. Recommendations for in-house and home inductions to ensure safe and effective treatment.

• Buprenorphine
• Opioid Dependency
• Induction Guidelines
• Patient Education
• Withdrawal Management

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1. Buprenorphine Induction Continued: Microdosing NORTHERN COLORADO MAT LEARNING FORUM Lesley Brooks, MD Thursday, April 4, 2019 Colorado Opioid Synergy Larimer and Weld

2. Short acting opioids Most patients dependent on short-acting opioids. Heroin and many Rx narcotics = short acting. Abstinence timing for short-acting is 12-16 hours; for intermediate-acting is 17-24 hours To Review Bupe induction and maintenance checklist Need for withdrawal prior to induction Home vs Office Induction Microdosing Long acting opioids Due to longer action, patients must abstain longer before induction. May need "comfort" medicine (e.g., non-opioid analgesics, non-benzo anxiolytic, antidiarrheal agents, antiemetics, antispasmodics) for withdrawal after the first day until a stable dose Treat induction for long-acting opioids with care, as precipitated withdrawal more likely. Methadone (MTD) = long-acting. Transferring from MTD requires additional steps: taper to 30-40mg daily, then abstain for 36hrs after last dose. Ref: https://www.btodrems.com/Portal/Content%20Library/Appropriate%20Use%20Checklist.pdf Colorado Opioid Synergy Larimer and Weld

3. In-House / Office Induction J. Dubin COWS score 12-15 1st dose 2-4 mg under observation in office or inpatient setting. Observe in office for at least 1 hr, document effect. Repeat dose to comfort. 1stday s dose may range from 2-16 mg. Lower doses required in those with lower level of physical dependence. If withdrawal occurs after patient leaves the office, request patient return to clinic. Avoid this complication by taking the time to assure moderate withdrawal discomfort prior to the first dose. Remain in contact with patient by phone during 1st 1-2 days; adjust dose as needed over next 5-7d Give sufficient medication only until the next visit, within 3-7 days Colorado Opioid Synergy Larimer and Weld

4. Home Inductions J. Dubin Good candidate: Pt who has had patient education Previously treated patients known to be reliable patients who demonstrate knowledge of the risks of unobserved induction, willing to come to the office in the event of problems. Suboptimal candidate: patient has expressed significant fear of withdrawal May starting buprenorphine too early and causing a precipitated withdrawal. Provide explicit written instructions and SOWS/COWS Maintain close telephone/office contact with patient during course of induction Have patient return within 2-7 days of starting buprenorphine. Colorado Opioid Synergy Larimer and Weld

5. Home Induction: Home Induction: Education Handout Education Handout Example Example Educate pt on when to start bupe (in AM) - # hrs since last dose, - sx they should have prior to starting Describe what dose to take, how to take it - 4-8 mg under tongue Explain - when they will feel better - what to do if they don t (another dose in 1-3 hrs) - Max dose on 1st day - when to call the clinic - when to return for follow up Colorado Opioid Synergy Larimer and Weld

6. Microdosing Methadone (MTD) Works well for many, improved retention in treatment over bupe requires no abstinence period Limitations include daily dosing, geographic location, drug-drug interactions, careful titration to avoid side effects Buprenorphine (bupe) Also works well for many; slightly less effective at retention in treatment vs MTD Improved side effect profile, few drug-drug interactions requires presence of withdrawal; can itself precipitate w/d if abstinence timing insufficient Colorado Opioid Synergy Larimer and Weld

7. Induction Challenges Conventional Bupe Induction Despite precautions, can lead to precipitated w/d Can be a difficult experience for the person with OUD Can lead to risk of relapse to illicit opioid use Hammig et al (University of Basel Psychiatric Hospital, Switzerland) Published Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method , Substance Use and Rehabilitation, 2016 Will review this method today Colorado Opioid Synergy Larimer and Weld

8. Hammig et al: Microdosing Hypotheses Based on slow bupe kinetics, observation that small doses of IV bupe did not produce w/d in MTD patients Repetitive admin of small bupe doses w/ short (12hr) intervals should not w/d Bupe will accumulate at the receptor Over time, increasing amounts of full agonist will be replaced by bupe at receptor Proposed: overlapping induction of bupe in persons with ongoing use of street heroin or high-dose full agonist (MTD) w/o severe w/d sx Colorado Opioid Synergy Larimer and Weld

9. Hammig: Case 1 F, middle-class, Swiss family Hx of sexual abuse, PTSD, poly-SUD (cocaine, psilocybin, MDMA, cannabis, heroin), MDD w/ suicide attempt, bulimia all b/w 12-18yrs Mult attempts at bupe maintenance; bupe mono as bup/ntx not avail in SZ 30yrs of age at time of presentation to Univ Basel, 3g/day street heroin Conventional induction severe w/d, trauma-related flashbacks, anxiety Returned to heroin use after 2 weeks Again returned to program for re-induction but nervous about tolerability of process Colorado Opioid Synergy Larimer and Weld

10. Hammig: Case 1 Implemented Bernese Method/Microdose Induction Started with low dose bupe 0.2mg overlapping with heroin use small daily dose increases abrupt cessation of heroin/full agonist when target dose reached Case 1 stabilized at 12mg/d bupe Has relapsed several times w/ heroin, re-initiated bupe with Bernese method Experienced another episode of MDD, tx d with escitalopram & therapy Stable off heroin x 2.5yrs Colorado Opioid Synergy Larimer and Weld

11. Microdosing Microdosing Protocol Protocol Hammig group asked pharmacy to cut tablets into quarters Pharmacy board does not allow pharmacists to cut - Ask for guidance Colorado Opioid Synergy Larimer and Weld

12. Microdosing Microdosing Protocol Protocol Hammig group asked pharmacy to cut tablets into quarters Pharmacy board does not allow pharmacists to cut - Ask for guidance Day # Bupe Dose Bupe Dose-2mg (#tabs) Methadone Dose 1 0.5mg X 1 1/4 tab 30mg 2 0.5mg BID 1/4 tab X 2 25mg 3 1mg BID 1/ 2 tab X 2 20mg 4 2mg BID 1 tab X 2 15mg 5 4mg BID 1 tabs X 4 10mg 6 8mg Daily 4 tabs 5mg (last day) Colorado Opioid Synergy Larimer and Weld

13. Hammig: Naltrexone Microdosing Protocol Case 1 desired complete abstinence; wanted to initiate NTX for craving Hammig et al. assumed NTX could be started similar to overlapping bupe induction Case 1 tapered off bupe to 2mg/d then Used small amounts of NTX ( scratched off from 50mg tablet ) with daily increases Did not develop w/d sx or cravings Stopped bupe, increased NTX to 25mg/d After several months, stopped NTX 3yrs 3mos abstinent at publication Colorado Opioid Synergy Larimer and Weld

14. Naltrexone Naltrexone Microdosing Microdosing Oral naltrexone comes in 50mg tablets Microdosing of 0.125, 0.250, 1mg, etc requires compounding pharamcy Local solution for microdosing ?? Day # NTX Dose Methadone Dose 1 0.125/0.250mg 30mg 2 0.125/0.250mg 25mg 3 0.125/0.250mg 20mg 4 0.125/0.250mg 15mg 5 0.125/0.250mg 10mg 6 0.125/0.250mg 5mg (last day) 2008, Mannelli et al Colorado Opioid Synergy Larimer and Weld

15. MAT MAT Which MAT is best for my patient? Which MAT is best for my patient? No clearly established criteria. Venue as important as Rx. Some things to consider - What is your patient s preference? - How stable is your patient? - Is the person pregnant? - What is their treatment history? - How severe is their use disorder? - Are there co-occurring disorders? - How strong is their support system? - What kind of and how much structure do they need? - Can the person stop using long enough for induction? Colorado Opioid Synergy Larimer and Weld

16. References 1. H mmig, Robert et al. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Substance abuse and rehabilitation vol. 7 99- 105. 20 Jul. 2016, doi:10.2147/SAR.S109919 2. Mannelli, Paolo et al. Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial. Addiction biology vol. 14,2 (2008): 204-13. doi:10.1111/j.1369-1600.2008.00119.x Colorado Opioid Synergy Larimer and Weld

17. Thank you! Thank you! Who s got a case? Who s got a case? Colorado Opioid Synergy Larimer and Weld