Buprenorphine All You Ever Wanted to Know

1. BuprenorphineAll You Ever Wanted to Know Susan Gurney MSN, NP-C, PMHNP-BC

2. Objectives • Describe the mechanism of action of buprenorphine • List the criteria needed to diagnosis opioid use disorder • Describe how NPs can begin prescribing buprenorphine

3. Maine had 418 OD deaths in 2017, 42 more than 2016 According to the U.S. CDC there were 63,632 drug overdose deaths in the United States in 2016 174 deaths per day; one death every 8.28 minutes 42,249 (66.4%) were due to opioids.  More deaths than those as a result of firearms, homicide, suicide, and motor vehicle crashes.

4. Buprenorphine • The Drug Addiction Treatment Act of 2000 (DATA 2000) permitted office-based prescribing of schedules III drugs approved for addiction by physicians who are certified in addiction medicine or addiction psychiatry, or have completed at least 8 hours of authorized training.

5. Buprenorphine • July 2016 The Comprehensive Addiction and Recovery Act (CARA) was signed into law • Expanded prescribing privileges to nurse practitioners (NPs) and physician assistants (PAs) for five years (until October 1, 2021). NPs and PAs must complete 24 hours of training to be eligible for a waiver to prescribe. A bill has been submitted (4/4/18) to make prescribing permanent for NPs and PAs. • Grants for naloxone • Addressed primary prevention to recovery support as well as PMP

7. Mechanism of Action • Buprenorphine is a partial opioid agonist at the Mu receptor • Has a strong affinity and will displace full Mu receptor agonist like methadone and heroin • Affinity is the strength with which a drug physically binds to a receptor • Dissociation is the speed (slow or fast) of disengagement or uncoupling of a drug from the receptor • Buprenorphine dissociates slowly

8. Mechanism of Action • Bup may reduce the effects of other opioids taken due to its high affinity for and slow dissociation from the Mu receptor • Naloxone is an opioid antagonist • It is used to discourage IV use of Bup in opioid dependent people • Serum concentration reaches peak 30 to 60 min after SL • Elimination half-life is 37 hours

9. Adverse Effects • Sedation • Nausea • Constipation • Headache • Diaphoresis • Itching • Numb mouth • Swollen &/or painful tongue • Withdrawal sx if abrupt D/C

10. Drug Interactions • Potent 3A4 inhibitor • Erythromycin, Ketoconazole and HIV proteas inhibitors can cause substantial increases in plasma concentration

11. Opioid Use Disorder • A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12 month period • Opioids taken in larger amts or over longer period than was intended • Persistent desire or unsuccessful efforts to cut down • Great deal of time spent- obtaining/recovering • Craving

12. Opioid Use Disorder • Failure to fulfill major role obligations at work, school or home • Continued use despite of problems • Important social, occupational or rec activities are given up • Recurrent use in hazardous situations • Continued use despite physical or psych problems • Tolerance • Withdrawal

13. How to Qualify to Prescribe • Take the free 24 hour on-line course • www.asam.org/education/live-online-cme/buprenorphine • www.aanp.org ce center- buprenorphine waiver course • SAMSHA in turn forwards this to DEA to get x-waiver

14. How to Apply for Waiver • SAMSHA Buprenorphine Waiver Notification needs to be filled out (Notification of Intent (NOI) online), need DEA and certificate from 24 hour course • https://www.samhsa.gov/medication-assisted-treatment/qualify-nps-pas-waiver • Effective  February 27, 2017 SAMHSA began accepting electronic submissions of the NOI. These waiver applications are forwarded to the DEA, which will assign the NP or PA a special identification number. DEA # with X in front of it. • My DEA # MG 1035066, X waiver # XG1035066 • DEA regulations require this number to be included on all buprenorphine prescriptions for opioid use disorder treatment, with the NP’s/PA’s DEA registration number.

15. Writing the Prescription • X number needs to be on prescription • In Maine, pharmacies are requiring that Chronic and Exemption D also be written on prescription due to law of July 2017 • These are part of the Opioid Prescription Requirements and exemption codes • DX code: F11.20 (Opioid dependence, uncomplicated) • D is Medication assisted treatment • It says under D that acute/chronic not required, but some pharmacies are requiring it

16. Also Consider…. • Check PMP before initial prescription and every 3 months • Offer prescription for Narcan • Narcan Nasal Spray 4mg #1 (2 pack) Administer as directed prn for suspected OD DX: F11.20 Refills: 2 • MaineCare requires PA if client filling more than 1 time in a month

17. Risk Evaluation and Mitigation Strategy (REMS) Induction checklist • Meet diagnostic criteria • Discuss risks of bup and side effects • Storage, keep away from children • Induction doses, prescribe limited amount • Schedule next visit

18. Risk Evaluation and Mitigation Strategy (REMS) Maintenance checklist • Consider pill/film count • Assess appropriateness of dosage • Conduct urine drug screens • Assess participation in counseling • Assess whether benefits of treatment outweigh risks • Assess whether client is making progress towards goals • Schedule next visit

19. Formulations • 2002 Buprenorphine/naloxone (Suboxone) SL tablets and Buprenorphine SL tablets (Subutex) tablets d/c by manufacturer once films became available • 2010 Buprenorphine/naloxone SL films • 2013 Buprenorphine/naloxone SL tablets (Zubsolv) • 2014 Buprenorphine/naloxone buccal films (Bunavail) • 2016 Buprenorphine implants (Probuphine) • 2017 Buprenorphine extended release SC inj (Sublocade)

20. Formulations • Zubsolv and Bunavail have greater bioavailability than Suboxone, meaning they deliver more buprenorphine to the bloodstream, thus achieving the same effect as the original product with lower doses • i.e. 5.7mg/1.4mg of Zubsolv and 4.2mg/0.7mg of Bunavail provide the same buprenorphine exposure as 8mg/2mg Suboxone

21. Probuphine • 4 subdermal implants x1 for 6 months- need to be on stable buprenorphine doses of 8mg/2mg or less for at least 3 m • contains 74.2 mg of buprenorphine (equivalent to 80 mg of bup hcl) • All HCP performing insertions &/or removals of PROBUPHINE must successfully complete a live training program, & demonstrate procedural competency prior to inserting or removing the implants

22. Sublocade • For abdominal subcutaneous injection only • Need to be on stable dose of buprenorphine of at least 8mg • 300mg for 1st 2 months, then maintenance dose of 100mg monthly • Steady state is achieved at 4 to 6 months • Patients discontinuing Sublocade may have detectable plasma levels of buprenorphine for 12 months or longer • Cost approximately 1500$ a month

23. Sublocade • Forms a solid mass upon contact with body fluids • Only available through restricted program due to risk of serious harm/death that could result from IV use • Healthcare settings and pharmacies that order and dispense Sublocade must be certified in the Sublocade REMS Program • In the event the depot needs to be removed, it can be surgically excised under local anesthesia within 14 days of injection

24. Buprenorphine • Indivior- recommends day 1 8mg/2mg, increase to 2 strips day 2 • Sublingual administration during induction, if in maintenance phase may take buccally • If taking 2 films at a time, place the 2nd one under tongue on opposite side. Avoid letting the films touch • While dissolving, do not chew or swallow the film

26. Buprenorphine • Induction- clients need to be in visible withdrawals • COWS score should be 7 or greater to start • The ClinicalOpiateWithdrawalScale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiatewithdrawal and monitor these symptoms over time.

27. The 11 symptoms measured by the COWS are: • Resting pulse rate (taken after the patient has been sitting or lying down for 60 seconds); measured on a scale of 0-4, from 80 or below, to a pulse rate greater than 120 • Sweating over the previous 30 minutes, not accounted for by room temperature or the patient’s physical activity; measured on a scale of 0-4, from no reports of chills or flushing, to sweat streaming off the patient’s face • Restlessness observed during assessment; measured on a scale of 0-4, from the patient being able to sit still, to the patient being unable to sit still for more than a few seconds • Patient’s pupil size; measured from 0-4, from the pupils being pinned or of a standard size for room light, to the pupils being so dilated that only the rim of the iris can be seen • Bone or joint aches if the patient had been previously experiencing pain; measured on a scale of 0-4, from no such aches being present, to the patient constantly rubbing joints and being unable to sit still because of pain

28. The 11 symptoms measured by the COWS are: • Runny nose or teary eyes, not accounted for by symptoms of a cold or allergies; measured from 0-4, from no such symptoms being present, to the nose constantly running or discharge from the eyes streaming down the cheeks • Gastrointestinal upset over the previous 30 minutes; measured on a scale of 0-4, from no such symptoms being present, to multiple instances of diarrhea or vomiting • Observable tremors when the hands are outstretched; measured on a scale of 0-4, from no visible tremors, to full twitching of muscles • Yawning during assessment; measured from 0-4, from no yawning, to yawning several times per minute • Anxiety or irritability; measured from 0-4, from no anxiety, to the patient being so anxious or irritable that the assessment is difficult to conduct • Goosebumps on the skin; measured on a scale of 0-4, from the skin being smooth, to “prominent” bumps and bristling of the hairs on the skin

31. Buprenorphine • If switching from methadone treatment program I taper client to 20mg methadone and client does not dose for 2 days prior • Some providers taper to 30mg and do not dose for 2 or 3 days prior

32. Goals of Induction • Discontinue or markedly reduce use of other opioids • Decrease cravings • Decrease withdrawal symptoms • Minimal/no side effects

33. Buprenorphine • For most clients, I start 8mg/2mg • To avoid precipitating withdrawals, I tell them to cut strip in ½ and just take that, if no withdrawals, take the other ½ 1 to 2 hours later • In office inductions can be done • Have it in stock or write prescription and have client return • ¼ strip, reassess COWS

34. Buprenorphine • Generally see them 1 week later • Assess for any withdrawals

35. Pregnancy • Emerging evidence supports the use of buprenorphine for opioid assisted treatment during pregnancy • If prescribed it is off label so should do an informed consent with client • Buprenorphine is recommended without naloxone, to prevent any neonatal exposure to naloxone, especially if injected • Advantages of Bup over methadone • Less severe Neonatal Abstinence Syndrome (NAS) • Lower risk of overdose • Ability to have a prescription vs daily dosing of methadone at a clinic • Fewer drug interactions

36. Pregnancy • Rates of Neonatal Abstinence Syndrome(NAS) are similar among infants born to methadone- vs. buprenorphine-maintained mothers, but symptoms were less severe for infants whose mothers were treated with buprenorphine maintenance (Thomas et al. 2014). • Total NAS score and several specific signs (tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) have been observed to be significantly more frequent in methadone-exposed neonates, while sneezing was more frequent among buprenorphine-exposed neonates • Infants who were breastfed had less severe NAS and were less likely to require pharmacologic treatment (23.1% vs. 30.0%) than infants who were bottlefed

37. Counseling • Individual, group, IOP (intensive outpatient program) • The more clients do for their recovery, the more successful they will be

38. Resources • PCSS-MAT (Providers clinical support system-medication assisted treatment)- PCSS’s mission is to increase healthcare providers’ knowledge and skills in the prevention, identification, and treatment of substance use disorders with a focus on opioid use disorders. • Clinical coaching program to provide guidance to prescribers and key health professionals on prevention, identification, and treatment of opioid use disorder. • The Outpatient Treatment Manual for the Care of Opioid-Dependent Pregnant Women with Buprenorphine by Alane O’Connor DNP and William Alto MD

39. Heroin

40. These are bundles- 1 Gr Heroin, it is sold as a ticket (small bag)- 20$ a ticket in Central Maine. 10 to 20 tickets to a bundle

43. Track Marks • Look for long sleeves in summer • Prominent bruised veins • Red marks hands

44. Thank you for your attentionsgurney@roadrunner.com