Suboxone) in the Outpatient Setting

Patricia Caddy, MD, Kesh Smith, MD

A quick-reference guide for prescribing buprenorphine/ naloxone (Suboxone) in the outpatient setting

By empowering physicians to treat opioid use disorder in their own clinics, an easy-to-use resource supporting Suboxone induction could have important impacts on both individual and public health.

ABSTRACT: British Columbia is in peer-reviewed articles grounded in ritish Columbia is experienc- the midst of an opioid crisis. Treat- evidence-based medicine. While the ing one of the greatest pub- ment with buprenorphine/naloxone project was undertaken at the Na- Blic health emergencies in its (Suboxone) is one way to mitigate the naimo site of the UBC Island Medical history. Opioid-related deaths con- many harms resulting from opioid Program, key stakeholders consid- tinue to climb because opioid use is use, yet studies show that few phy- ered during development included increasing and illicit drugs are be- sicians are prescribing this medi- primary care physicians, trainees, ing contaminated with devastatingly cation. A quick-reference guide for and people with opioid use disorder potent opioids such as fentanyl and physicians that supports Suboxone throughout BC. Feedback was obtai- carfentanil. In 2017 the province had induction in the outpatient setting ned from physicians with an interest 1210 illicit drug overdose deaths as- was proposed as part of a Resident in addiction medicine. The clinical sociated with fentanyl compared with 1 Scholar Project required for comple- tool that resulted from the project 667 the year before. ting a residency in family medicine is intended to be a supplementary In April 2016 the sharply rising at the University of British Colum- resource, not a stand-alone one. Fur- number of deaths related to fentanyl bia. The project involved the crea- ther improvement of the tool is ex- led BC’s provincial health officer to tion and evaluation of a teaching pected in future as physicians using declare an “opioid overdose emer- tool for physicians based on recent the resource participate in a self- gency.” Shortly after, the special li- guidelines from the British Columbia test survey and feedback process. censure requirement was removed for Centre on Substance Use as well as prescribing Suboxone, a formulation of buprenorphine and naloxone com- bined at a ratio of 4:1 and administered sublingually. This made it legal

Dr Caddy is currently completing her residency in family medicine at the Nanaimo site of the University of British Columbia Family Medicine Residency Program. Dr Smith has completed his residency in family medicine at the Nanaimo site of the Uni- versity of British Columbia Family Medicine This article has been peer reviewed. Residency Program.

392 bc medical journal vol. 60 no. 8, october 2018 bcmj.org A quick-reference guide for prescribing buprenorphine/naloxone (Suboxone) in the outpatient setting

for any physician with prescribing proposed was intended to serve as a tween patients with this disorder and privileges to use Suboxone to treat supplement to published guidelines their physicians. opioid use disorder, a complex neu- and online courses, and to provide robehavioral illness recognized in the contact information for specialists Literature review DSM-5. Opioid use disorder is char- in addiction medicine should further Studies have shown that treatment acterized not only by negative chang- support be needed. By empowering with opioid substitution therapy leads es in a person’s ability to function at physicians to treat opioid use disor- to sustained abstinence from opioid home, at work, and in society, but by der in their own clinics, the resource use, reduced risk of morbidity and the development of physical toler- could reduce referrals to more spe- mortality, and better rates of treat- ance and withdrawal symptoms. Sub- cialized clinics, which is preferable ment retention when compared with oxone can be used to manage these symptoms because the buprenorphine it contains is a partial agonist at the mu opioid receptor with a very high binding affinity. Once bound, buprenorphine activates the receptor less than a full agonist such as morphine, When prescribed skillfully, fentanyl, heroin, or methadone. The Suboxone results in the naloxone content of Suboxone deters tampering and misuse as it is active reduction or elimination of only when administered parenterally, withdrawal symptoms. often precipitating withdrawal symptoms in the opioid-tolerant user. When prescribed skillfully, Sub- oxone results in the reduction or elimination of withdrawal symptoms without providing the reinforcing “high” or potenially deadly sedative according to a meta-analysis pub- abstinence or withdrawal-only ther- effects of a full agonist, and is now lished by Srivastava and colleagues, apies.2 Suboxone and methadone are recommended as first-line therapy for who state that “opioid addiction is considered equally efficacious for the management of opioid use disor- best managed in a primary care set- opioid substitution therapy and are der in BC.2 ting.”3 A resource supporting Subox- the two medications recommended in one use could have important impacts the latest British Columbia guideline. Suboxone prescribing on both individual and public health. The College of Physicians and Sur- resource Greater access to and acceptance of geons of BC recommends completing A resource designed to reduce bar- Suboxone as an opioid substitution an online Suboxone training program, riers to treating opioid use disorder therapy initiated by family physicians although this is not required in order with Suboxone in the family prac- could increase the number of patients to prescribe Suboxone. Still, relative- tice setting was proposed as part of treated for addiction, thus reducing ly few family physicians in BC pre- the Resident Scholar Project required overdose deaths and bloodborne ill- scribe the medication. Although no for the University of British Colum- nesses stemming from use of IV drug studies have been conducted in BC bia family medicine residency pro- paraphernalia. This could also im- specifically, several qualitative stud- gram. A quick-reference guide was prove treatment retention, a factor ies elsewhere have examined the bar- seen as a way to fill the knowledge associated with higher rates of ab- riers that prevent family doctors from gap felt by many would-be prescrib- stinence.4 Finally, greater physician prescribing Suboxone to their patients. ers considering starting a patient on willingness to prescribe Suboxone One of the most commonly cited bar- Suboxone and to support clinicians could lessen the stigma associated riers is a perceived lack of know- in need of a refresher who fear “de- with seeking treatment for opioid use ledge and confidence in the induction skilling” after taking a course on how disorder, creating opportunities for a phases of treatment.4-11 Respondents to prescribe this medication. The tool stronger therapeutic relationship be- in a 2012 Australian study identified

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“de-skilling” after undertaking Sub- tiveness.16 There was nothing in the scale (COWS), suggestions for miti- oxone training as another barrier.5 literature about using information-at- gating precipitated withdrawal, and Other barriers frequently identified a-glance guides designed to support considerations such as urine drug were a lack of local mental health sup- physician prescribing of Suboxone testing (UDT) and take-home doses port services/institutional support,7,9-11 for opioid use disorder, making it or “carries” versus daily witnessed a lack of time (and space) in a busy likely that the resource produced for ingestions. practice,5,7-9,11 fear of misuse and di- this Resident Scholar Project is the The information in our clinical version of the medication,7,8 a lack of first of its kind. tool is based on A Guideline for interest in prescribing,8 and practice the Clinical Management of Opioid 2 partners unwilling to allow Subox- Development of resource Use Disorder published by the Brit- one prescribing in a shared clinic.5,7,9 We obtained the information includ- ish Columbia Centre on Substance A lack of addiction specialist support ed in our resource from provincial Use and the BC Ministry of Health, was a further barrier highlighted in guidelines, as well as peer-reviewed as well as online Suboxone training.17 The recommendations within the BC guideline that were used to inform our resource are of moderate to strong quality according to the GRADE cri- What little literature could be found teria for evidence appraisal.2 regarding physician education for In order to give clinicians the opportunity to test their knowledge after Suboxone prescribing practices using our guide, we provided a link to tended to focus on chronic pain a self-test on Suboxone induction, as well as an email address where they rather than opioid use disorder. can send feedback they may have for us about the tool itself.

Strengths and limitations of resource a number of studies.7-10 These stud- articles grounded in evidence-based The novel resource that we developed ies are from countries comparable to medicine. In addition, we asked phys- for the project is portable, easy to Canada, and we believe the results are icians already practising addiction reproduce, easy to use, and has the generalizable to British Columbia. medicine to review our tool to ensure potential to influence clinician pre- Therefore, any intervention aimed that we were providing only high- scribing practices. Creating the tool at encouraging family physicians to quality information. While the pro- provided us with the opportunity become Suboxone prescribers must ject was undertaken at the Nanaimo to further refine our skills as phys- reduce some of these barriers. While site of the UBC Family Medicine ician-teachers and physician-leaders. it is not currently known how best to Residency Program, key stakehold- The time-limited nature of the pro- do this, or which barriers should be ers considered during development ject restricted uptake of the resource the focus, there is clearly a knowledge included primary care physicians, throughout the community despite gap that needs to be addressed to help trainees, and people with opioid use our best efforts, and also meant we more family physicians prescribe disorder throughout BC. were unable to quantitatively assess Suboxone. Based on the information col- the impact of our tool on physician What little literature could be lected and analyzed, we developed prescribing. found regarding physician education a document to assist physicians with for Suboxone prescribing practices in-office assessment, Suboxone in- Further improvement of tended to focus on chronic pain rath- duction, and maintenance ( Figure ). resource er than opioid use disorder,12 other The resource includes induction al- We plan to collect feedback from teaching modalities (e.g., web-based gorithms for Day 1 and Day 2, ad- users of the quick-reference guide or telehealth-based courses),12-15 or vice on gauging withdrawal severity and hope to implement suggested standard guidelines and their effec- using the clinical opiate withdrawal improvements in future iterations of

394 bc medical journal vol. 60 no. 8, october 2018 bcmj.org A quick-reference guide for prescribing buprenorphine/naloxone (Suboxone) in the outpatient setting

Prescribing suboxone in the outPatient setting a quick-reference guide to in-office induction By Patricia Caddy, MD, and Kesh Smith, MD Adapted from A Guideline for the Clinical Management of Opioid Use Disorder published by the British Columbia Centre on Substance Abuse and the BC Ministry of Health, June 2017

Confirm opioid use assessment Check PharmaNet ✓ disorder using DSM–5 Suboxone • Combination of buprenorphine and naloxone at ratio of 4:1 Rule out Obtain substance • Available in 2.0 mg/0.5 mg and 8 mg/2 mg contraindications use history sublingual (SL) tablets + + • Allergy to Suboxone • Tablets may be split if necessary • All drugs used, including • Pregnancy (relative contra- ethanol (EtOH), nicotine, • May take up to 10 min to dissolve completely indication to induction but (no talking, smoking, or swallowing at this time) benzodiazapines not to continuation) • Age and amount of • Absorption better with moistened mouth • Severe liver dysfunction first use, current use • Naloxone prevents IM/IV diversion of drug and is • Severe respiratory distress not active when taken SL, so does not protect • Any periods of abstinence • Acute EtOH intoxication • Treatment history patient from overdose • Goals • Max dose approved in Canada 24 mg/6 mg daily

Order/review lab test results • CBC • Hep A/B/C serologies • Electrolytes • STI panel (including HIV) • Renal panel • Urine drug test • Liver panel

induction: day 1 Precipitated withdrawal • 1–2 days required for baseline assessment and initiation • Can occur due to replacement of full opioid receptor • Day 1 max dose 12 mg/3 mg agonist (e.g., heroin, fentanyl, morphine) with partial agonist that binds with a higher affinity (e.g., Suboxone, Confirm Give Suboxone SL 4 mg/1 mg methadone) √ COWS* score > 12 ~ 2 hours Symptoms √ No contraindications Withdrawal symptoms • Similar to opiate withdrawal (i.e., increased heart gone? √ No long-acting opioids rate, sweating, agitation, diarrhea, tremor, unease, used for > 30 hours restlessness, tearing, runny nose, vomiting, goose flesh) No Yes • Can range from mild to severe Additional doses Go to Day 2 • Can be very distressing and discouraging for patients needed • Largely reversible with higher doses of Suboxone or other opioid *COWS = clinical opiate withdrawal scale • Avoid by ensuring adequate withdrawal before A validated clinical tool used to determine severity of opiate induction (COWS > 12), starting Suboxone at a lower withdrawal, available free online at www.bccsu.ca/wp-content/ dose (2.0 mg/0.5 mg), and reassessing more frequently uploads/2017/06/BC-OUD-Guidelines_June2017.pdf Treatment (see Appendix 6 of A Guideline for the Clinical Management • Explain what has happened of Opioid Use Disorder) • Provide empathetic/compassionate/apologetic support • Manage symptoms with clonidine, loperamide. Avoid benzodiazepines • Encourage/motivate patient to try again soon

Figure (Page 1 of 2). In-office assessment, Suboxone induction, and maintenance document

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induction: day 2 onwards • If adequate symptom relief not achieved over Day 1 and 2, additional days (usually no more than 2) may be required • Day 2 max dose 16 mg/4 mg

Withdrawal symptoms recurred since last dose?

No Yes • Give Day 1 total dose again • Give Day 1 total plus another to complete induction. This will dose Suboxone SL 4 mg/1 mg Yes be the ongoing daily dose • Induction complete • Consider titration up to ~ 2 hours • Give Day 2 total as ongoing dose, optimal dose (≥ 12 mg/3 mg) or titrate up to ≥ 12 mg/3 mg for improved retention in treatment for improved retention in Withdrawal symptoms gone? treatment • May increase dose every 1–3 days, or less frequently ~ 2 hours No • Additional doses needed • Give Suboxone SL 4 mg/1 mg

maintenance Goal = once-daily dosing, no withdrawal between doses. Ideally, dose ≥ 12 mg/3 mg

Monitor • Order urine drug testing (UDT) • Check PharmaNet regularly to ensure prescriptions • Assess for readiness for take-home dosing (“carries”), see below are filled, no doctor shopping, etc. considerations take-home doses (“carries”)

Urine drug testing (UDT): • Suboxone ingestion commonly witnessed • Urine drug testing expected for patients on at the pharmacy but take-home doses may Suboxone to objectively document licit/illicit be prescribed drug use • Take-home “carries” appropriate for patients • UDT not to be used punitively but to facilitate who demonstrate biopsychosocial stability, open communication have not missed doses, are abstinent from • Perform point-of-care UDT at least monthly illicit drugs, have a secure place to store • Consider ordering confirmatory testing for their medication unexpected results (false positives do occur)

for additional suPPort and resources...

To speak to an expert in BC: To test your new knowledge of Suboxone induction, Rapid Access to Consultative Expertise go to www.surveymonkey.com/r/BXHVWVT (RACE) line: 1 877 696-2131 To help us improve this guide, please send your To see the latest guidelines, research, feedback to [email protected]. and provincial resources: Sender information will not be included when British Columbia Centre on Substance Use feedback is considered. www.bccsu.ca

Figure (Page 2 of 2). In-office assessment, Suboxone induction, and maintenance document

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the resource. We also hope that in fu- References prenorphine: Clinical practices and barri- ture we or another resident group can 1. BC Coroner Service. Fentanyl-detected il- ers. J Gen Intern Med 2008;23:1393-1398. quantitatively assess the effectiveness licit drug overdose deaths January 1, 2012 12. Dubin RE, Flannery J. ECHO Ontario of this resource and its impact on pre- to December 31, 2017. Accessed 12 July chronic pain & opioid stewardship: Provid- scribing practices in the community. 2018. www2.gov.bc.ca/assets/gov/ ing access and building capacity for pri- public-safety-and-emergency-services/ mary care providers in underserviced, ru- Summary death-investigation/statistical/fentanyl ral, and remote communities. Stud Health A quick-reference guide for physi- -detected-overdose.pdf. Technol Inform 2015;209:15-22. cians that supports Suboxone induc- 2. British Columbia Centre on Substance 13. Kahan M, Gomes T, Juurlink DN, et al. Ef- tion in the outpatient setting was Use. A guideline for the clinical manage- fect of a course-based intervention and proposed to encourage prescribing of ment of opioid use disorder. Accessed 12 effect of medical regulation on physicians’ this medication to mitigate the many July 2018. www.bccsu.ca/wp-content/ opioid prescribing. Can Fam Physician harms resulting from opioid use di- uploads/2017/06/BC-OUD-Guidelines_ 2013;59:e231-239. sorder. Data for the resource were June2017.pdf. 14. Webster J. Prescriber education on opi- obtained from A Guideline for the 3. Srivastava A, Kahan M, Nader M. Primary oids. Ann Intern Med 2012;157:917. Clinical Management of Opioid Use care management of opioid use dis 15. Stoner SA, Mikko AT, Carpenter KM. Disorder, as well as other provincial orders: Abstinence, methadone, or Web-based training for primary care pro- guidelines and peer-reviewed articles. buprenorphine-naloxone? Can Fam Phy- viders on screening, brief intervention, The needs of primary care physicians, sician 2017;63:200. and referral to treatment (SBIRT) for alco- trainees, and people with opioid use 4. Hser Y, Evans E, Grella C, et al. Long-term hol, tobacco, and other drugs. J Subst disorder were considered during de- course of opioid addiction. Harv Rev Psy- Abuse Treat 2014;47:362-370. velopment, and feedback was obtai- chiatry 2015;23:76. 16. Pinto D, Heleno B, Rodrigues DS, et al. An ned from physicians with an interest 5. Longman C, Temple-Smith M, Gilchrist G, open cluster-randomized, 18-month trial in addiction medicine. The clinical Lintzeris N. Reluctant to train, reluctant to to compare the effectiveness of educa- tool that resulted from the project is prescribe: Barriers to general practitioner tional outreach visits with usual guideline intended to be a supplementary re- prescribing of opioid substitution therapy. dissemination to improve family physician source, not a stand-alone one. Further Aust J Prim Health 2012;18:346-351. prescribing. Implement Sci 2014;9:10. improvement of the tool is expected 6. Huhn AS, Dunn KE. Why aren’t physicians 17. INDIVIOR Canada Ltd. Welcome to the as physicians using the resource par- prescribing more buprenorphine? J Subst Suboxone training program. Accessed ticipate in a self-test survey and feed- Abuse Treat 2017;78:1-7. 12 July 2018. www.suboxonetraining back process. 7. Andrilla CHA, Coulthard C, Larson EH. program.ca/en/. Barriers rural physicians face prescribing Acknowledgments buprenorphine for opioid use disorder. We would like to thank Dr Marcus Barron, Ann Fam Med 2017;15:359-362. a family medicine and addiction medicine 8. DeFlavio JR, Rolin SA, Nordstron BR, Ka- physician who acted as our research proj- zal LA Jr. Analysis of barriers to adoption ect advisor, for providing guidance and of buprenorphine maintenance therapy by input as the resource was created and family physicians. Rural Remote Health helping to solicit feedback from other 2015;15:3019. physicians who routinely treat opioid use 9. Hutchinson E, Catlin M, Cheng DM et al. disorder in the community. We would also Barriers to primary care physicians pre- like to thank the physicians who generous- scribing buprenorphine. Ann Fam Med ly provided comments and feedback on 2014;12:128-133. the quick-reference guide during develop- 10. Li X, Shorter D, Kosten TR, Taenzer P, et ment: Dr Elizabeth Plant, Dr Mark Mclean, al. Buprenorphine in the treatment of opi- Dr Patricia Mark, and Dr Marcus Barron. oid addiction: opportunities, challenges and strategies. Expert Opin Pharmacoth- Competing interests er 2014;15:2263-2275. None declared. 11. Walley AY, Alperen JK. Office-based management of opioid dependence with bu-

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