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Safe Opioid Prescribing and Managing Opioid Use Disorders Educational Rounds for Primary Care Physicians META:PHI 2015 About META:PHI Mentoring, Education, and Clinical Tools for Addiction: Primary Care–Hospital Integration • Goals: – Promote evidence-based addiction medicine treatment – Implement care pathways between the ED, hospital, WMS, primary care, and rapid access addiction medicine clinics • Seven sites in Ontario are currently involved, with plans to expand the spread of the project in the future • Funding and support provided by the Adopting Research to Improve Care (ARTIC) program (Council of Academic Hospitals of Ontario & Health Quality Ontario) https://www.porticonetwork.ca/web/meta-phi META:PHI 2015 Sign-In Sheet • META:PHI mailing list: Forum for project team and other health care providers to discuss clinical cases, policies, and events related to addiction • All attendees invited to participate: Write name/email address on sheet to be added META:PHI 2015 OVERVIEW META:PHI 2015 Opioid Prescribing in Canada • Drastic increase in Canadian opioid prescribing since 1990s • Substantial increases in opioid overdose deaths and prescription opioid addiction (1, 2) • PCPs’ prescribing practices contribute to harms • Set of evidence-based guidelines on opioid prescribing for chronic pain were developed by the National Opiate Use Guideline Group (3) – These guidelines have had little effect on overprescribing META:PHI 2015 Opioid Prescribing in Canada (cont’d) • Canada is world’s 2nd largest per capita consumer of opioids (4) • Ontario highest annual rate of high-dose oxycodone and fentanyl dispensing: 756 tablets and 112 patches per 1000 (5) • Opioid-related deaths in Ontario have risen from 127 in 1991 to 550 in 2010, a 242% rise (6) META:PHI 2015 Minimizing Risks of Opioid Therapy 1. Only prescribe to patients for whom opioids are likely to be safe and effective. 2. Always begin therapy with weak opioids. 3. When prescribing potent opioids, start with a low dose and titrate slowly. 4. Routinely monitor patients on opioid medications to ensure that they are experiencing meaningful benefit. 5. Provide patients with education on safely storing medication, preventing overdose, and the risks of sharing opioids with others. 6. Initiate appropriate treatment or facilitate referral for patients with an opioid use disorder. META:PHI 2015 INITIATING OPIOID THERAPY META:PHI 2015 Acute vs. Chronic Pain • Severity of acute pain determined by severity and extent of tissue damage/inflammation – Acetaminophen, NSAIDs, opioids, local anesthetics, and other treatments very effective • In chronic non-cancer pain (CNCP), psychological and cognitive factors influence pain perception – Opioids and other analgesics only modestly effective and rarely relieve pain completely – Effective non-pharmacological approaches: cognitive behavioural therapy, mindfulness meditation, physical modalities – Effective non-opioid medications: acetaminophen, NSAIDs, anticonvulsants, antidepressants META:PHI 2015 Opioids as Therapeutic Trial • Opioid prescribing = therapeutic trial – Continue if patient experiences meaningful benefit: • Improved function and reduction in pain severity of 2+ points on a ten-point scale without significant side effects – Taper and discontinue if patient has failed adequate trial of 2+ opioids; continued opioid prescribing puts patients at risk for long-term side effects and complications META:PHI 2015 Indications for Long-Term Opioid Therapy • Patient has well-defined pain condition (nociceptive or neuropathic) that… a. has been shown to respond to opioids b. causes both pain and disability • Non-opioid treatments are ineffective, contraindicated, or have intolerable side effects • Note: Potent opioids are not indicated for common pain conditions such as fibromyalgia, low back pain, and headaches – Benefits are minimal and are outweighed by the side effects META:PHI 2015 Prior to Prescribing Opioids • Ask about current and past use of alcohol and drugs • Ask about mood – Depressed patients may have heightened perception of pain and are less responsive to opioids • Check renal and respiratory status, especially risk of sleep apnea • In elderly patients, assess risk of falls • Consider tapering benzodiazepines • Ask about the impact of pain on activities of daily living META:PHI 2015 Prior to Prescribing Opioids (cont’d) • Reassess their response to non-opioid treatments: – Nociceptive pain: acetaminophen, NSAIDs, SNRIs – Neuropathic pain: anticonvulsants, SNRIs, TCAs – All pain: Mindfulness programs, graded exercise • Advise patients not to drink alcohol during titration • Warn patients to avoid driving for at least two hours after a dose in the first 1–2 weeks of treatment initiation and the first week of dose increase • Warn patients to keep their opioids safely stored (especially if they live with adolescents/young adults), and not to give any opioid medications to relatives or friends META:PHI 2015 Office Visits • See patient frequently during initiation and titration • At each office visit, ask about changes in: – Work, school, social activities, daily activities – Pain ratings on a 0–10 scale, at rest and with activity – Mood • Ask about side effects: – Sedation, dizziness, and other CNS effects – Constipation, nausea META:PHI 2015 OPIOID PRESCRIBING PROTOCOL META:PHI 2015 Immediate Release (IR) vs. Controlled Release (CR) • Initiate opioid trial with IR preparations • Maintain on IR for brief pain (less than 4 hours) or incident pain (triggered by activity) • For constant pain throughout the day, switch to CR • In long-term therapy for constant pain throughout the day, “breakthrough” IR medications should not exceed 10–30% of total daily opioid dose META:PHI 2015 Opioid Selection • Always initiate opioid treatment with “weak” opioids, i.e., oral preparations of codeine, tramadol (e.g., Tramacet, Ultram, Zytram XL), or buprenorphine patch (BuTrans) • If insufficient analgesia with first-line opioids, prescribe morphine (various generics), oxycodone (various generics, OxyNEO), or hydromorphone (e.g., Dilaudid, Hydromorph Contin, Jurnista) • Note: Morphine is contraindicated in patients with renal insufficiency META:PHI 2015 Opioid Selection (cont’d) • Some evidence suggests that hydromorphone and oxycodone have fewer cognitive effects than morphine in the elderly • Prescribing transdermal fentanyl (various generics, Duragesic) should be done with extreme caution, especially in the elderly and patients at high risk for opioid use disorder – Use only if the patient has taken at least 60–100 mg morphine equivalent daily (MED) of a potent opioid for at least 2 weeks META:PHI 2015 Opioid Initiation and Dose Titration Opioid Max initial dose Max dose increase Min days between increases Min IR dose before moving to CR Codeine 200 mg/d 50 mg/d 7 days IR, 14 days CR 150 mg Transdermal buprenorphine 5 μg/7d 5 µg/7d 7 days ------- Morphine* 40 mg/d 10 mg/d 7 days IR, 14 days CR 30 mg Oxycodone* 30 mg/d 5 mg/d IR, 10 mg/d CR 7 days IR, 14 days CR 20 mg Hydromorphone* 8 mg/d 1–2 mg/d IR, 2– 4 mg/d CR 7 days IR, 14 days CR 6 mg Tapentadol* IR 700 mg/d, 100 mg/d CR CR** 3 days CR ------- *Potent opioids should only be dispensed to patients currently taking weak opioids daily. All dose increases should be based on individual assessment. **CR: Start 50 mg bid in opioid-naïve, ≥50 mg bid if switching from other opioids. Maximum 250 mg bid. META:PHI 2015 Exert caution when switching from pure mu-opioids. Morphine Equivalency Opioid Analgesic equivalence value Morphine (reference) 30 mg Codeine 200 mg Oxycodone 20 mg Hydromorphone 6 mg Tapentadol No equivalence to morphine established, but CR has demonstrated comparable pain relief to oxycodone CR (dose ratio 5:1) Transdermal buprenorphine No equivalence to morphine established Transdermal fentanyl 25 μg/hr = 60–100 mg oral morphine per day META:PHI 2015 Optimal Dose • Increase dose if insufficient analgesia and no improvement in function • Optimal dose reached if: – Pain relief at least 2 points on 10-point scale, with no benefit from 1–2 additional dose increases – Improved functioning at work, school, and with family; increased physical activities – No major side effects • Optimal dose for most patients is 50–60 mg META:PHI 2015 Maximum (“Watchful”) Dose • Opioids have dose-related complications (e.g., overdose, sleep apnea, falls/fractures) • Watchful dose given by the Canadian Guideline is 200 mg MED • However, doses above 120 mg MED are strongly associated with an increased risk of overdose • At doses approaching 120 mg MED, reassess opioid’s analgesic effectiveness and side effects, and decide whether to maintain the dose or taper META:PHI 2015 Minimizing Adverse Effects 1. Falls in the elderly • Do not prescribe opioids to cognitively impaired patients unless dispensed and overseen by caregiver • Taper benzodiazepines • Avoid use of opioids at night if possible – If pain wakes patient up, prescribe smallest IR opioid dose and warn patients to take extra precautions when getting out of bed META:PHI 2015 Minimizing Adverse Effects (cont’d) 2. Overdose during initiation/increase • Educate patients on early signs of impending overdose: sedation, slowed speech, nodding off • Advise family to call 911 at first sign of overdose 3. Fatigue • Opioids cause fatigue either through direct sedating effect or by contributing to sleep apnea – Assess for sleep apnea – Reduce, discontinue, or switch opioid META:PHI 2015 Minimizing Adverse Effects (cont’d) 4. Constipation • Increase fibre, fluid, activity • If laxatives are needed, consider polyethylene glycol (Restorolax), sodium picosulphate (Dulcolax) or lactulose – Polyethylene glycol most effective for opioidinduced constipation META:PHI 2015 OPIOID TAPERING AND SWITCHING META:PHI 2015 Indications for Tapering • Patient has persistent severe pain and pain-related disability despite an adequate opioid dose (e.g., 60 mg/d MED), and patient has already failed on a trial of at least one opioid previously – Evidence suggests tapering improves pain, mood, and functioning in these circumstances • Patient has complication from opioid therapy (e.g., sleep apnea, sedation, dysphoria) • Part of structured opioid therapy for patients who are addicted or at high risk for addiction META:PHI 2015 Key Principles of Tapering • Taper by no more than 10% of total daily dose every 1–2 weeks • Keep dosing interval the same (e.g., tid, bid) • Use scheduled rather than PRN dosing • Endpoint of taper not necessarily abstinence but improved functioning, mood, and/or pain • Do not abruptly discontinue opioids under any circumstances – Risk of loss of tolerance and overdose META:PHI 2015 Tapering Protocol Formulation CR preferred (until low dose reached) Dosing interval Scheduled doses rather than PRN Keep dosing interval the same for as long as possible Advise patients not to skip doses Rate of taper Taper slowly (max 10% of total daily dose every 1-2 weeks) Let patient choose which dose is decreased (AM, PM, or HS) Taper even more slowly when 1/3 of total dose is reached Dispensing interval If patient runs out early, increase frequency to weekly, alternate day, or daily Endpoint of taper ≥ 60 mg MED (suggested watchful dose in elderly; controls pain with minimal side effects) Frequency of visits If possible, see patient prior to each dose decrease Approach Ask about withdrawal symptoms and benefits of tapering: more alert, less fatigued, improved mood, improved pain META:PHI 2015 Indications for Switching Opioids • Inadequate analgesic response to current opioid (< 2/10 pain relief, no improvement in function) despite a reasonable dose (e.g., 60 mg MED) – Patients who have had minimal analgesic response to a moderate dose are unlikely to benefit from further dose increases • Adverse effects with current opioid (e.g., constipation, sedation, falls) META:PHI 2015 Opioid Switching Protocol • Because patient will not be fully tolerant to new opioid, its MED should be 50% of MED of original • Example: When switching patient from 40 mg/d of oxycodone to hydromorphone: – – – – 40 mg/d oxycodone = 60 mg MED 60 mg MED = 12 mg/d hydromorphone 50% of hydromorphone 12 mg = 6 mg Therefore, start patient on 6 mg/d in divided doses • Ensure patient understands that taking extra doses is dangerous • Titrate dose as appropriate for opioid META:PHI 2015 OPIOID MISUSE AND WITHDRAWAL META:PHI 2015 Limiting Misuse and Diversion • Warn patients to store medication in secure location, not to show them to younger relatives, and not to share them with anyone • Avoid using fentanyl patches in elderly patients with younger adults at home – Used patches contain large amount of fentanyl; patches can be lifted off patient’s skin while they are sleeping • Without anyone else present, ask parents and grandparents on opioids if younger relatives could be using their medication, especially if patient requires high doses, runs out early, or is accompanied by younger adult to office visits META:PHI 2015 Features of Opioid Withdrawal Time course Symptoms start six hours after last use of IR opioid, peak at 2–3 days, and begin to resolve by 5–7 days (methadone withdrawal peaks on day 5, and bup/nx withdrawal peaks on day 7) Psychological symptoms can last for weeks Physical symptoms Flu-like: Myalgias, chills, sweating, nausea and vomiting, abdominal cramps, diarrhea Insomnia, anxiety and irritability, restlessness, dysphoria, craving Psychological symptoms Complications a. Suicide b. Overdose if opioids taken after a period of abstinence (loss of tolerance) c. Possible gastritis or peptic ulcer d. Acute exacerbation of cardiorespiratory illnesses, e.g., asthma, angina e. Exacerbation of psychiatric conditions: anxious patients may experience panic attacks, schizophrenic patients may experience psychosis, etc. META:PHI 2015 Prevention and Management of Opioid Withdrawal • Do not discontinue opioids abruptly; taper dose slowly • If patient in acute withdrawal, buprenorphine/naloxone (bup/nx) is safest and most effective treatment – Prior to administering bup/nx, ensure patient has not used opioids for at least 12–16 hours, and patient reports symptoms of withdrawal – Clinical Opioid Withdrawal Scale (COWS) used to monitor withdrawal severity (assess at baseline and at 30m, 2h, 4h) – Initial dose 2 mg sublingual (SL) – Dispense 2–4 mg SL in 2 hours if necessary; maximum 4 mg on first day – May taper over several days/weeks or maintain dose META:PHI 2015 Clinical Opioid Withdrawal Scale (COWS) (7) Resting heart rate (measure after lying or sitting for one minute) 0 HR ≤ 80 1 HR 81–100 Sweating (preceding 30m and not related to room temp/activity) 0 no report of chills or flushing 1 subjective report of chills or flushing 2 flushed or observable moistness on face 3 beads of sweat on brow or face 4 sweat streaming off face Restlessness (observe during assessment) 0 able to sit still 1 reports difficulty sitting still, but is able to do so 3 frequent shifting or extraneous movements of legs/arms 5 unable to sit still for more than a few seconds Pupil size 0 pupils pinned or normal size for room light 1 pupils larger than normal for room light 2 pupils moderately dilated 5 pupils so dilated that only the rim of the iris is visible META:PHI 2015 2 HR 101–120 4 HR > 120 COWS (cont’d) Bone or joint pain (not including existing joint pains) 0 not present 1 mild diffuse discomfort 2 patient reports severe diffuse aching of joints/ muscles 4 patient is rubbing joints / muscles plus unable to sit still due to discomfort Runny nose or tearing (not related to URTI or allergies) 0 not present 1 nasal stuffiness or unusually moist eyes 2 nose running or tearing 4 nose constantly running or tears streaming down cheeks GI upset (over last 30 minutes) 0 no GI symptoms 1 stomach cramps 2 nausea or loose stool 3 vomiting or diarrhoea 5 multiple episodes of vomiting or diarrhoea Tremor (observe outstretched hands) 0 no tremor 1 tremor can be felt, but not observed 2 slight tremor observable 4 gross META:PHI tremor2015 or muscle twitching COWS (cont’d) Yawning (observe during assessment) 0 no yawning 1 yawning once or twice during assessment 2 yawning 3+ times during assessment 4 yawning several times/minute Anxiety or irritability 0 none 1 patient reports increasing irritability or anxiousness 2 patient obviously irritable or anxious 4 patient so irritable or anxious that participation in the assessment is difficult Gooseflesh skin 0 skin is smooth 3 piloerection (goosebumps) of skin can be felt or hairs standing up on arms 5 prominent piloerection SCORE INTERPRETATION 5-12 13-24 Mild Moderate META:PHI 2015 25-36 > 36 Moderately severe Severe OPIOID ADDICTION META:PHI 2015 Identifying Patients • OUDs are difficult to diagnose if patient doesn’t disclose use • Maintain high index of suspicion with risk factors: – Younger, male, psychiatric comorbidity, concurrent or past addiction to other drugs, on high prescribed opioid doses • Common presentations: – Overdose, withdrawal, drug seeking, infections from injection drug use, depression and suicidal ideation, trauma META:PHI 2015 Indications of an OUD 1. Check for physical signs of opioid use: track marks, pinpoint pupils, slurred speech, nodding off (intoxication), restlessness (withdrawal) 2. Check pharmacy dispensing record for patients on Ontario Drug Benefits 3. Ask about opioid use and withdrawal symptoms META:PHI 2015 Symptoms and Behaviours of Problematic Opioid Use • Patient’s opioid dose high for underlying pain condition • Aberrant behaviours: Running out early, crushing/biting oral tabs, accessing opioids from other sources • Importance patient attaches to drug far outweighs analgesic benefit (e.g., strong resistance to tapering or switching current opioid) • Binge rather than scheduled opioid use • May be currently addicted to other drugs, e.g., alcohol META:PHI 2015 Symptoms and Behaviours of Problematic Opioid Use (cont’d) • • • • • Depressed and anxious Deteriorating mood and functioning Concerns expressed by family members Reports recurrent, frightening withdrawal symptoms May acknowledge that they experience immediate improvement in mood after taking opioid META:PHI 2015 Presenting OUD Diagnosis • Be clear and non-judgmental • Inform patient that their opioid use is harming them, and that treatment will improve their pain, mood, and functioning • Refer patient to treatment – Tell patient that if they do not engage in treatment you will perform an involuntary taper • Do not abruptly stop opioid prescribing – Taper dose with frequent (i.e., daily) dispensing META:PHI 2015 OUD Management Options 1. Abstinence-based psychosocial treatment 2. Structured opioid therapy 3. Opioid maintenance therapy META:PHI 2015 Abstinence-Based Psychosocial Treatment • Cessation of all alcohol and drugs (including opioid maintenance drugs methadone and bup/nx) • Less effective than opioid maintenance but often preferred by patients, and is sometimes a requirement for probation, etc. • Patients at increased risk for opioid overdose after leaving abstinence-based programs, so overdose prevention strategies are needed: – Do not inject – Take a much smaller opioid dose than usual – Take a test dose unless you got the drug directly from a doctor’s prescription – Don’t mix opioids with alcohol/benzodiazepines – Always have a friend with you if you inject or snort opioids – don’t use alone META:PHI 2015 Structured Opioid Therapy • Continued opioid prescribing under conditions that limit misuse • Preliminary evidence: effective, convenient for patients, and easier to organize than opioid substitution therapy • Refer for opioid substitution therapy if structured therapy fails • Indications: – Addicted to opioids or at high risk for addiction (younger, personal or strong family history of addiction, anxiety or mood disorder) – Has pain condition requiring opioid therapy – Only uses opioids supplied by one physician – Does not alter route of delivery (inject or crush oral tabs) – Is not currently addicted to alcohol or other drugs META:PHI 2015 Structured Opioid Therapy (cont’d) • Protocol: – Taper dose to below 200 mg MED (emphasize that patient will feel and function better with lower dose) – Dispense small amounts frequently (e.g., 1–2 times per week) – Do not refill if patient runs out early – Monitor closely with urine drug screens, pill counts, office visits – Switch to opioid maintenance therapy if structured opioid therapy fails (e.g., patient continues to access opioids from other sources) META:PHI 2015 Opioid Maintenance Therapy • Substituting illegal and/or euphoria-inducing opioid with longer-acting, less euphoric opioid (i.e., methadone or bup/nx) • Indications: – Failed at or not a candidate for structured opioid therapy – Acquires opioids from multiple sources (e.g., other doctors, friends and relatives, the street) – Injects or crushes oral tablets – Currently misusing alcohol or other drugs META:PHI 2015 PRESCRIBING BUPRENORPHINE/NALOXONE META:PHI 2015 Buprenorphine • Partial opioid agonist with ceiling effect – Unlike full agonists (e.g., morphine), even very high doses rarely cause respiratory depression unless combined with alcohol/sedating drugs • Appropriate dose relieves withdrawal symptoms and cravings for 24 hours without causing euphoria • Binds very tightly to the opioid receptors, displacing other opioids that occupy the receptor site – Minimizes psychoactive effect of other opioids taken concurrently • Has slow onset and long duration of action • Side effects similar to other opioids: nausea, constipation, sedation META:PHI 2015 Initiation Protocol • Physician must ensure that patient has no opioid in their serum before taking the first dose to avoid precipitated withdrawal – Precipitated withdrawal is rarely severe or dangerous, but patients who experience it are reluctant to try bup/nx again • Give first dose in office setting, if feasible – 12-16 hours since last IR dose, 24 hours since last CR dose – Patient reports typical withdrawal symptoms – COWS score of 12+ • First dose: 4 mg SL (dose may take several minutes to dissolve) • Reassess in 2 hours. – If patient improved but still in withdrawal, give another 4 mg to take in office or at home – Maximum dose first day: 12 mg META:PHI 2015 Initiation Protocol (cont’d) • Reassess in 1–3 days – Increase dose by 2–4 mg at each visit if patient reports withdrawal symptoms or cravings towards end of dosing interval – Each dose increase should increase duration of relief from withdrawal and cravings • Optimal maintenance dose usually 8–16 mg SL OD; maximum dose 24 mg SL OD – Optimal dose should relieve withdrawal symptoms and cravings for 24 hours without causing significant sedation or other side effects META:PHI 2015 Initiation Protocol (cont’d) • At beginning of therapy, bup/nx should be dispensed daily under observation by pharmacist – If patient unable to attend daily, arrange supervised dispensing at home by nurse or reliable relative – Take-home doses may be prescribed once patient is at optimal dose and has stopped unauthorized opioid use • Arrange frequent office visits for counselling and urine drug screen monitoring META:PHI 2015 Bup/nx Prescriptions • • • • • Patient’s name, date of birth, and health card number Pharmacy address and fax number Dose Start and end dates Days of the week patient takes dose at pharmacy under observation of pharmacist, and days patient takes dose at home – Stable patients usually attend pharmacy once a week to take one observed dose and take six doses home • Limited use (LU) code for patients on ODB: 437 (for patients who have failed, have significant intolerance of, have a contraindication to, or are at high risk for toxicity with methadone) or 438 (when a methadone maintenance program is not available or accessible)META:PHI 2015 Sample Bup/nx Prescription Jennifer Chen MD Main St. Clinic Phone: (555) 555-1234 Fax: (555) 555-1237 Date: June 2, 2016 Jonathan Smith HC 1234 567 890 QI DOB Apr. 25, 1974 Shoppers Drug Mart, 123 Elm St. Fax: (555) 555-9834 Buprenorphine/naloxone 8/2 mg 1 tab SL OD June 2, 2016 – June 8, 2016 inclusive Dispense daily observed LU 437 Jennifer Chen MD CPSO 12345 META:PHI 2015 Management of Stable Patients on Bup/nx • Ask about withdrawal symptoms or cravings – Sometimes patients require minor dose adjustments of 2–4 mg/day • Ask about alcohol and cannabis use (usually not tested on urine drug screen) • Ask about overall mood and functioning • Manage chronic medical conditions (e.g., hepatitis C) or psychiatric conditions (e.g., anxiety, depression) • Perform regular screening and health maintenance (e.g., pap tests, mammograms, immunizations, etc.) META:PHI 2015 Urine Drug Screening • Review urine drug screen results – Stable patients should leave one urine sample per month – Review unexpected results with patient and, if necessary, with addiction physician Result Interpretation Absence of norbuprenorphine Noncompliance or diversion Presence of opioids or benzodiazepines Presence of cocaine or crystal methamphetamine Action If diversion suspected, resume daily supervised dispensing Consider consult with addiction physician Innocent slip If inadvertent, warn patients not to take meds from Early relapse family or friends Increase testing frequency If meds used for mood control: Assess adequacy of bup/nx dose Counsel about avoiding triggers Assess mood Increase testing frequency If persists, reduce number of take-home doses Possible stimulant use Consider consult with addiction physician META:PHI 2015 disorder Tapering Bup/nx: Indications • Patient wants to taper • Patient has at least six months without any substance use • Patient is socially stable and has a supportive family or social network • Patient has a stable mood and good coping strategies • Patient has minimal contact with drug users META:PHI 2015 Tapering Bup/nx: Protocol • Decrease by small amounts, e.g., 2 mg or even 1 mg (half of a 2 mg tablet) at a time • Leave at least two weeks, preferably longer, between dose decreases • Put taper on hold at patient’s request, or if patient experiences withdrawal symptoms or cravings • Return to original dose if patient begins using opioids again, even in small amounts or intermittently • Provide regular support and encouragement • Emphasize that it is not a “failure” if taper has to be held or reversed, and it is safe and acceptable to remain on bup/nx for long periods when necessary META:PHI 2015 References 1. 2. 3. 4. 5. 6. 7. Dasgupta N, Kramer ED, Zalman MA, Carino S, Jr., Smith MY, Haddox JD, et al. Association between non-medical and prescriptive usage of opioids. Drug and alcohol dependence. 2006;82(2):135-42. Avoiding abuse, achieving a balance: tackling the opioid public health crisis. Toronto: College of Physicians and Surgeons of Ontario, 2010. Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-cancer Pain. National Opioid Use Guideline Group, 2010. Canada: National Opioid Use Guideline Group, 2010. International Narcotics Control Board. Narcotics Drugs: Estimated World Requirements for 2013; Statistics for 2011. 2013. New York: United Nations. Gomes T, Mamdani MM, Paterson JM, et al. Trends in high-dose opioid prescribing in Canada. Can Fam Physician 2014;60:826-32. Gomes T, Mamdani MM, Dhalla IA, Cornish S, Paterson JM, Juurlink DN. The burden of premature opioid-related mortality. Addiction (Abingdon, England). 2014;109(9):1482-8. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). Journal of psychoactive drugs. 2003;35(2):253-9. META:PHI 2015