Opioid-Related Disorders
Clinical Snapshot
Opioid use disorder (OUD) is a problematic pattern of opioid use causing clinically significant impairment or distress, diagnosed using DSM-5-TR criteria over any 12-month period.[1] It sits alongside two related but distinct presentations covered in this chapter: opioid intoxication/overdose (a medical emergency requiring immediate naloxone and emergency medical services) and opioid withdrawal (uncomfortable but rarely life-threatening on its own, though it is the single biggest driver of relapse and subsequent overdose when a patient's tolerance has already dropped).
Opioid agonist therapy (OAT) — buprenorphine/naloxone or methadone — is the standard of care and is strongly recommended over withdrawal management (detoxification) alone, which carries a high risk of relapse, morbidity, and overdose death once tolerance is lost.[2] The 2024 update to the Canadian national guideline made a genuine, practice-changing change from the 2018 version: methadone and buprenorphine/naloxone are now equally recommended first-line treatments (previously buprenorphine was preferred whenever feasible), based on evidence that the two are similarly effective, each with a different risk profile clinicians must plan around — higher attrition after the first month with buprenorphine, higher mortality risk in the first month with methadone.[2] Pharmacists are central to this care: dispensing and (where required) witnessing OAT ingestion, catching missed-dose and interaction risks, and being a frontline source of take-home naloxone and harm reduction supplies.
Complications of untreated OUD include overdose; increased risk of oral, throat, liver, colon, and breast cancers; infections (aspiration pneumonia, cellulitis, tuberculosis, hepatitis B and C, HIV); complications of injection drug use (vasculitis, emboli); psychiatric comorbidity (depression, anxiety); suicide; trauma; sexual dysfunction; poor nutrition; severe constipation; and insomnia/sleep apnea.
Recognize the Condition
The 3 opioid-related presentations (DSM-5-TR)
Opioid use disorder
At least 2 of 11 problematic-use criteria within a 12-month period causing clinically significant impairment or distress — including taking more/longer than intended, unsuccessful efforts to cut down, craving, tolerance, and withdrawal (tolerance/withdrawal are not counted toward the diagnosis if opioids are being taken solely under appropriate medical supervision). Severity: mild (2-3 criteria), moderate (4-5), severe (6 or more).[1]
Opioid intoxication/overdose
Recent opioid use with behavioural/psychological change (initial euphoria, then apathy, dysphoria, psychomotor agitation or retardation, impaired judgment) plus pupillary constriction (or dilation from anoxia in severe overdose) and drowsiness/coma, slurred speech, or impaired attention/memory.[1]
Opioid withdrawal
Cessation or reduction of heavy, prolonged opioid use (or administration of an opioid antagonist) followed within minutes to days by 3 or more of: dysphoric mood, nausea/vomiting, muscle aches, lacrimation/rhinorrhea, pupillary dilation/piloerection/sweating, diarrhea, yawning, fever, or insomnia, causing significant distress or impairment.[1]
Distinguishing overdose from withdrawal at the bedside
| Feature | Opioid intoxication/overdose | Opioid withdrawal |
|---|---|---|
| Pupils | Constricted (pinpoint); dilated only with severe anoxia | Dilated |
| Respiratory rate | Depressed, often <12/min | Normal or increased |
| Level of consciousness | Drowsy, unresponsive, or comatose | Alert, anxious, restless |
| Skin | Pale, cool, sometimes cyanotic | Sweating, piloerection ("gooseflesh") |
| Immediate management | Naloxone, airway support, emergency services | Opioid agonist therapy initiation, symptomatic adjuncts |
Risk Factors
- Personal or family history of a substance use disorder.
- Chronic pain managed with prescription opioids, particularly at higher doses or for longer durations.
- Co-occurring mental health conditions — depression, anxiety, post-traumatic stress disorder.
- History of trauma or adverse childhood experiences.
- Concurrent use of alcohol, benzodiazepines, or stimulants.
- Social determinants of health — housing instability, unemployment, involvement with the criminal justice system.
- Prior opioid overdose.
- Recent loss of opioid tolerance — release from a correctional facility, discharge from withdrawal management or residential treatment, or a recent hospitalization without continued opioid agonist therapy.
- Injection drug use.
- Exposure to an unregulated drug supply contaminated with fentanyl or other potent synthetic opioids.
Red Flags & Refer
Any of the following requires immediate action, not routine follow-up:
- Suspected opioid overdose — unresponsive or severely sedated, respiratory rate under 12/min, pinpoint pupils, cyanosis: call 911 immediately, give naloxone, and begin rescue breathing/CPR if the patient is not breathing or has no pulse.
- Severe withdrawal with dehydration, intractable vomiting, or inability to tolerate oral intake.
- Precipitated withdrawal during buprenorphine induction that is not resolving with standard management (additional buprenorphine dosing, symptomatic adjuncts).
- Pregnancy with untreated or unstable opioid use disorder — urgent referral to an integrated perinatal addiction program; do not attempt to taper or detoxify a pregnant patient.
- Suicidal ideation or intent.
- Signs of neonatal opioid withdrawal syndrome in an infant exposed to opioids in utero (high-pitched cry, irritability, poor feeding, tremor) — refer to the birth facility/pediatric team immediately.
- Concurrent high-dose opioid agonist therapy with ongoing benzodiazepine, alcohol, or other sedative use — additive respiratory depression and overdose risk requiring urgent reassessment of the treatment plan, not simple continuation.
Assessment & Diagnosis
History
- Pattern of opioid use — specific opioid(s), route, amount, frequency, and duration; time and amount of most recent use (critical for timing buprenorphine induction safely).
- Other substance use, including alcohol, benzodiazepines, and stimulants.
- Prior opioid agonist therapy, withdrawal management, or overdose history.
- Mental health history and current symptoms.
- Psychosocial context — housing, employment, social supports, involvement with the justice system.
- Pregnancy status in any patient of childbearing potential.
- Validated screening tools: CAGE-AID (CAGE questions adapted for drug use) and the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool can structure this history.
Physical examination
Look for signs of current intoxication or withdrawal, injection sites/track marks, and complications (cellulitis, abscess, endocarditis murmurs, signs of aspiration).
Grading withdrawal severity: the Clinical Opiate Withdrawal Scale (COWS)
COWS is an 11-item, clinician-scored tool used to grade the severity of opioid withdrawal and — critically — to help time the first dose of buprenorphine/naloxone so it is not given too early (see Choose Initial Treatment for how the score is used).[3]
| Item | Scoring (select the single best-fitting level) |
|---|---|
| Resting pulse rate | 0 = ≤80 bpm; 1 = 81-100; 2 = 101-120; 4 = >120 |
| Sweating (not from room temperature/activity) | 0 = none; 1 = subjective chills/flushing; 2 = flushed or visibly moist face; 3 = beads of sweat on brow/face; 4 = sweat streaming off face |
| Restlessness | 0 = able to sit still; 1 = reports difficulty but can sit still; 3 = frequent shifting of legs/arms; 5 = unable to sit still for more than a few seconds |
| Pupil size | 0 = normal/pinned for room light; 1 = possibly larger than normal; 2 = moderately dilated; 5 = so dilated only the iris rim is visible |
| Bone or joint aches (additional component attributable to withdrawal only) | 0 = not present; 1 = mild diffuse discomfort; 2 = severe diffuse aching; 4 = rubbing joints/muscles, unable to sit still from discomfort |
| Runny nose or tearing (not from cold/allergies) | 0 = not present; 1 = nasal stuffiness or moist eyes; 2 = nose running or tearing; 4 = constantly running or streaming |
| GI upset (over the last 30 minutes) | 0 = none; 1 = stomach cramps; 2 = nausea or loose stool; 3 = vomiting or diarrhea; 5 = multiple episodes of vomiting or diarrhea |
| Tremor (outstretched hands) | 0 = none; 1 = can be felt but not observed; 2 = slight, observable; 4 = gross tremor or muscle twitching |
| Yawning | 0 = none; 1 = once or twice; 2 = 3 or more times; 4 = several times per minute |
| Anxiety or irritability | 0 = none; 1 = reports increasing irritability/anxiousness; 2 = obviously irritable/anxious; 4 = so irritable that participating in the assessment is difficult |
| Gooseflesh skin | 0 = skin smooth; 3 = piloerection can be felt/hairs standing up; 5 = prominent piloerection |
Total score is the sum of all 11 items. 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; over 36 = severe withdrawal. A score over 12 (at least moderate withdrawal) is generally required before giving the first traditional-induction dose of buprenorphine/naloxone.[3]
Investigations
- Pregnancy test in anyone of childbearing potential.
- CBC, renal and liver function, electrolytes, magnesium, and phosphate.
- Bloodborne pathogen testing — HIV, hepatitis B, hepatitis C.
- Urine drug testing for opioids and other substances (e.g., benzodiazepines); consider fentanyl-specific testing given the contamination of the unregulated drug supply.
- Baseline ECG before starting methadone, given its QTc-prolongation risk, and periodically thereafter with dose escalation or when interacting drugs are added.
- Chest x-ray, CT head, or abdominal imaging only as clinically indicated by history/exam findings — not routinely.
Treatment Targets
- Engage the patient in opioid agonist therapy aligned with their own goals (cessation or reduction).
- Prevent fatal and non-fatal opioid overdose.
- Treat opioid withdrawal safely without precipitating it.
- Assess and treat medical and psychiatric comorbidities.
- Reduce or eliminate use of unregulated/illicit opioids.
- Retain the patient in treatment — the minimum recommended treatment duration is 12 months, and many patients need long-term or indefinite therapy given high relapse rates even after a year.
- Offer psychosocial support and harm reduction services as part of an integrated continuum of care, without making either a precondition for receiving opioid agonist therapy.
- Prevent vertical transmission of infection and neonatal complications when the patient is pregnant.
Choose Initial Treatment
Opioid agonist therapy versus withdrawal management alone
Standard of care offer opioid agonist therapy (buprenorphine/naloxone or methadone) to every patient with moderate-to-severe opioid use disorder. Do not offer withdrawal management (detoxification) as a stand-alone treatment — it carries a substantially higher rate of relapse, morbidity, and overdose death once tolerance is lost, compared with ongoing opioid agonist therapy.[2] If a patient nonetheless pursues withdrawal management, offer a supervised slow opioid agonist taper with close follow-up, and restart opioid agonist therapy immediately if relapse risk emerges.[2]
Buprenorphine/naloxone versus methadone
Both are equally recommended 1st-line options — base the choice on patient preference, prior treatment experience, comorbidities, and access. Buprenorphine/naloxone has a wider safety margin (partial agonist with a ceiling effect on respiratory depression) but a higher rate of attrition after the first month, so offer to switch to methadone if a patient on buprenorphine is struggling to stay engaged. Methadone has a higher risk of overdose death specifically in the first month of treatment (before full tolerance to the new dose is established) and requires baseline/periodic ECG monitoring for QTc prolongation, but is associated with slightly higher long-term treatment retention.[2]
Induction timing and avoiding precipitated withdrawal (buprenorphine/naloxone)
Buprenorphine has a higher affinity but lower intrinsic activity at the mu-opioid receptor than full agonists (heroin, fentanyl, oxycodone, methadone). Given too early, it displaces the full agonist and causes a net drop in opioid effect — precipitated withdrawal, which can be severe. For a traditional induction, wait until the patient has at least moderate withdrawal (COWS over 12) before the first dose; recommended minimum abstinence from the last opioid dose is 12 hours for short-acting opioids (heroin, oxycodone, hydromorphone), 24 hours for intermediate-acting opioids or fentanyl (confirmed or suspected), and 48-72 hours for methadone.[4]
For patients unwilling or unable to tolerate a pre-induction withdrawal period — including many patients using fentanyl, who are at particularly high risk of precipitated withdrawal even after reaching COWS over 12 — use a low-dose (microdosing) induction protocol instead. This "Bernese method" approach starts with very small buprenorphine/naloxone doses (e.g., 0.5 mg/0.125 mg) while the patient continues their usual full-agonist opioid unchanged, then up-titrates gradually over about a week until a full dose is reached and the full agonist is stopped — this does not require any pre-induction withdrawal period.[5]
Titration to a therapeutic maintenance dose
For buprenorphine/naloxone, titrate by 2 mg/0.5 mg-4 mg/1 mg increments to a usual maintenance range of 12-24 mg/day, up to 32 mg/8 mg/day for patients with high opioid tolerance (e.g., regular fentanyl use). For methadone, titrate cautiously — a maximum of 15 mg every 3 days for patients with established high tolerance (slowing to 10 mg every 3-5 days once the daily dose reaches about 85 mg), or 5-10 mg every 3-5 days for patients with lower or unknown tolerance — to a usual maintenance range of 60-120 mg/day, with some fentanyl-exposed patients needing higher doses under specialist guidance.[4]
Second-line and alternative options
2nd line — use when buprenorphine/naloxone and methadone are not suitable or have failed: slow-release oral morphine (the 24-hour extended-release formulation only), prescribed by or with the support of an experienced addiction-medicine clinician.[2]
Special situation: oral naltrexone can be discussed as an adjunct option for patients who decline or are not on standard opioid agonist therapy and have already completed withdrawal from opioids.[2]
Naloxone: offer it to everyone
Offer a take-home naloxone kit and training to every patient with opioid use disorder — regardless of which treatment (if any) they choose — and to their household members, support people, and anyone else who might witness an overdose.[6]
Non-Pharmacologic Treatment
Patient-centred, stigma-free engagement
Approach opioid use disorder as a medical condition, not a moral failing. Assess readiness for change and use motivational-interviewing techniques matched to the patient's current stage.
| Stage of change | Approach |
|---|---|
| Precontemplation | Encourage open discussion of opioid use without confrontation or judgment. |
| Contemplation | Help the patient weigh pros/cons; reinforce any "change talk" positively. |
| Preparation | Discuss concrete treatment options, including opioid agonist therapy and psychosocial supports; address concerns. |
| Action | Monitor progress, reinforce successes, troubleshoot difficulties. |
| Maintenance | Continue reinforcement; build relapse-prevention skills and a support network. |
| Relapse | Normalize relapse as part of the disease process, not a failure; help the patient re-enter the preparation stage rather than reinforcing shame. |
Psychosocial interventions
Offer psychosocial treatments and supports as adjuncts to opioid agonist therapy — psychoeducation, cognitive behavioural therapy, motivational enhancement therapy, relapse-prevention training, trauma-informed therapy, peer/mutual-aid support (e.g., Narcotics Anonymous), and family therapy. Psychosocial treatment should never be made mandatory or used as a barrier to receiving opioid agonist therapy — patients who want medication without a mandated counselling component should still receive it.
Harm reduction principles
Offer harm reduction as part of the continuum of care for every patient, independent of their treatment goals or current substance use status — harm reduction is not contingent on a patient pursuing abstinence.
- Take-home naloxone kits and overdose-response training.
- Provision of sterile drug-use equipment (needles/syringes, other supplies).
- Overdose prevention education — using with someone present, avoiding mixing with other sedatives, starting with a test dose after any period of reduced tolerance.
- Referral to supervised consumption or overdose prevention sites and drug-checking services where locally available.
- Bloodborne pathogen testing and vaccination (hepatitis B) as indicated.
Special Populations
Pregnancy
Screen universally for substance use at the first prenatal visit. Opioid agonist therapy is the standard of care in pregnancy, the same as in non-pregnant patients — do not taper or attempt to detoxify a pregnant patient, since withdrawal carries a real risk of spontaneous abortion and fetal distress. Pregnant people not already in treatment should be encouraged to start opioid agonist therapy as soon as possible.[2] Evidence does not clearly favour buprenorphine or methadone over the other for pregnancy outcomes, so either can be offered as first-line therapy.[2][7] A single-entity buprenorphine tablet (without naloxone) is theoretically preferred when available, but is not practically accessible in Canada, so the combination buprenorphine/naloxone tablet is continued. Recommend early epidural analgesia in labour for patients on opioid agonist therapy, since it can help mitigate the hyperalgesia associated with chronic opioid exposure.[7]
Neonatal opioid withdrawal syndrome (NOWS)
NOWS is neonatal withdrawal from in-utero opioid exposure. Onset is usually 48-72 hours after birth for most opioids and 4-14 days for methadone, and its severity does not correlate with the maternal maintenance dose. Features include a high-pitched cry, irritability, insomnia, hypertonia, tremor, vomiting, diarrhea, feeding problems, sweating, and tachypnea — evaluate for alternative causes (sepsis, hypoglycemia, hypocalcemia) before attributing symptoms to NOWS alone. The modified Finnegan Neonatal Abstinence Scoring System is the most widely used scoring tool, assessed every 2-4 hours in an inpatient setting. Nonpharmacologic care is standard first-line management: rooming-in with parents, swaddling, gentle rocking, frequent small feeds, and a quiet, low-light environment. For moderate-to-severe withdrawal, pharmacologic treatment (an oral opioid such as morphine or methadone) is directed by the inpatient neonatology/pediatric team.
Breastfeeding
Both methadone and buprenorphine are compatible with breastfeeding provided the patient has no other contraindication (e.g., is HIV-negative) and the infant is monitored for sedation and respiratory depression. Methadone transfers into breast milk at a low proportion of the maternal dose; buprenorphine transfer is even lower.
Adolescents
Current national guidance is scoped to adults 18 and older. Adolescents with opioid use disorder need referral to a specialized addiction pediatrics or youth addiction service rather than adult dosing extrapolation.
Older adults
Opioids and benzodiazepines are the prescription drugs most often associated with a substance use disorder in older adults, who are more sensitive to sedation and at higher risk of falls and cognitive impairment. Screen with collateral information from family/caregivers where possible — substance use disorders are commonly underdiagnosed in this group. Opioid agonist therapy remains standard, but use a slower dose-escalation schedule for patients over about 55 years of age.
Hepatic and renal impairment
Methadone is metabolized hepatically and eliminated largely via the gastrointestinal tract, so significant renal impairment does not usually require dose adjustment, but hepatic impairment warrants caution and slower titration. Buprenorphine is also hepatically metabolized (CYP3A4) — use caution and monitor closely in significant hepatic impairment. Naloxone dosing is unchanged in renal or hepatic impairment.
Monitoring & Follow-Up
See patients at least weekly during induction and periods of active dose titration (in person or virtually), decreasing frequency as clinical stability is achieved. At every visit, review substance use (patient report and, when indicated, urine drug testing), adequacy of dose control (withdrawal symptoms, cravings, sedation), adherence, and psychosocial stability. For methadone specifically, obtain a baseline ECG and repeat with significant dose escalation or new QTc-prolonging interacting drugs, and have a low threshold to reassess in person if there is any concern about toxicity (peak effect around 3 hours post-dose). Pharmacists dispensing opioid agonist therapy should notify the prescriber of missed doses per provincial regulation — missed-dose protocols determine whether a dose can simply resume or whether re-titration from a lower dose is needed, since tolerance is lost quickly once dosing is interrupted. Reassess and replenish take-home naloxone supply at follow-up visits. Periodically re-screen for bloodborne pathogens if ongoing risk factors are present, and continue to monitor for and treat co-occurring mental health conditions.
Common Errors to Avoid
- Offering withdrawal management (detoxification) alone without a plan for ongoing opioid agonist therapy — the single highest-risk error, given the sharp rise in overdose risk once tolerance is lost.
- Starting buprenorphine/naloxone before adequate withdrawal (COWS over 12) without using a validated low-dose (microdosing) protocol instead — precipitates withdrawal.
- Underdosing methadone or buprenorphine/naloxone out of excess caution, leaving the patient in withdrawal and prompting a return to unregulated opioid use, which paradoxically increases overdose risk.
- Treating clonidine as adequate opioid agonist therapy on its own — it is a symptomatic adjunct only and does not address craving or the underlying disorder.
- Failing to offer a take-home naloxone kit at every opioid agonist therapy initiation, and to the patient's household/support contacts.
- Stopping opioid agonist therapy abruptly rather than using a slow, individualized taper when a patient wishes to discontinue.
- Making psychosocial counselling mandatory as a precondition for receiving opioid agonist therapy.
- Missing methadone's QTc-prolongation risk — not obtaining a baseline ECG or checking for interacting drugs before and during dose escalation.
- Attempting to taper or detoxify a pregnant patient with opioid use disorder rather than continuing or initiating opioid agonist therapy.
- Treating a single missed dose the same as a prolonged treatment gap — apply the individualized missed-dose protocol rather than reflexively discontinuing therapy.
- Using the transdermal buprenorphine patch or buccal buprenorphine film — approved for chronic pain, not opioid use disorder — as a substitute for sublingual buprenorphine/naloxone.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Opioid Agonists (Full Agonist)
First-line and second-line long-term maintenance therapy.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Methadone | Starting dose (no/low tolerance, opioid-naive, high toxicity risk): 5-10 mg/day PO Starting dose (unknown/moderate tolerance): 10-20 mg/day PO Starting dose (known high tolerance, active opioid use): 20-30 mg/day PO Starting dose (known very high tolerance, e.g. prior methadone experience plus current fentanyl use): 30-40 mg/day PO; higher only with specialist input Dose escalation (established high tolerance): Up to 15 mg every 3 days, slowing to a maximum of 10 mg every 3-5 days once the daily dose reaches about 85 mg Dose escalation (lower/unknown tolerance): 5-10 mg every 3-5 days Maintenance: Usual range 60-120 mg/day PO once daily; some patients using fentanyl need higher doses under specialist guidance Children: Not established for opioid use disorder — pediatric/adolescent OUD requires a specialized addiction pediatrics referral | Sedation, respiratory depression (highest risk during induction/dose changes), QTc prolongation, hypotension, diaphoresis, constipation, sexual dysfunction | Long half-life causes delayed peak effect after each dose change — do not increase again before the current dose has had time to take full effect. Numerous CYP3A4/2B6 drug interactions. Typically requires daily witnessed ingestion during induction, per provincial regulation. |
| Slow-release oral morphine | Initial dose: 30-400 mg/day PO, depending on opioid tolerance (limit to 200 mg if combined with methadone) Titration: Increase by 30-200 mg every 48 hours as needed and tolerated (limit increases to 100 mg if combined with methadone) Maintenance: Usual range 60-1200 mg/day PO once daily as monotherapy; lower doses if combined with methadone Children: Not established for opioid use disorder — pediatric/adolescent OUD requires a specialized addiction pediatrics referral | Sedation, respiratory depression, hypotension, diaphoresis, constipation | Requires the 24-hour extended-release formulation (e.g., Kadian) — immediate-release morphine dosing does not apply. Second-line option, reserved for patients where buprenorphine/naloxone and methadone are unsuitable or ineffective; prescribe only with addiction-medicine experience or specialist support. |
Partial Opioid Agonist
First-line maintenance therapy; wider safety margin than full agonists due to a ceiling effect on respiratory depression, but must be started at the right time to avoid precipitated withdrawal.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Buprenorphine/naloxone | Traditional induction, day 1 (standard risk): 4 mg/1 mg SL as the first dose; give additional 2 mg/0.5 mg-4 mg/1 mg doses if withdrawal is not relieved within 1-3 hours Traditional induction, day 1 (higher precipitated-withdrawal risk, e.g. fentanyl use): 2 mg/0.5 mg SL as the first dose Traditional induction, day 2 onward: Repeat the prior day's total dose; add 2 mg/0.5 mg-4 mg/1 mg if withdrawal persists, up to a usual maximum of 24 mg/6 mg (up to 32 mg/8 mg for high-tolerance fentanyl-exposed patients under specialist guidance) Low-dose (microdosing) induction: Start 0.5 mg/0.125 mg SL once or twice daily while continuing the full-agonist opioid unchanged; up-titrate gradually over about a week per a structured protocol, then stop the full-agonist opioid once a full buprenorphine/naloxone dose is reached Maintenance: 12-24 mg/day SL once daily; up to 32 mg/8 mg/day for patients with high opioid tolerance Children: Not established for opioid use disorder — pediatric/adolescent OUD requires a specialized addiction pediatrics referral | Precipitated withdrawal if started too early, headache, nausea, constipation, hyperhidrosis, sleep disturbance, respiratory depression (lower risk than full agonists but still possible with other CNS depressants) | Sublingual technique: place under the tongue until fully dissolved (up to 10-15 minutes); avoid food, drink, or smoking until dissolved. Stable patients on 12mg/3mg/day or less may be candidates for alternate-day dosing. Missed-dose retitration and witnessed-ingestion requirements follow provincial regulation. |
| Buprenorphine (transdermal patch / buccal film) | Use in opioid use disorder: Not indicated — do not use | Not applicable to this indication | The transdermal patch and buccal soluble film formulations of buprenorphine are approved in Canada for chronic pain, not for opioid use disorder. Do not substitute either for sublingual buprenorphine/naloxone when treating opioid use disorder. |
Opioid Antagonists
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Naloxone | Adults, intramuscular: 0.4 mg IM into a large muscle; repeat every 2-3 minutes as needed Adults, intranasal: 1 spray (4 mg) into one nostril; repeat with a new device in the alternate nostril every 2-3 minutes as needed Children: 0.1 mg/kg IV/IM/SC (maximum single dose 2 mg); repeat every 2-3 minutes as needed | Precipitated opioid withdrawal (nausea, vomiting, sweating, tachycardia, reversal of analgesia); rarely pulmonary edema or arrhythmia after abrupt reversal in a physically dependent patient | Duration of action (about 20-90 minutes) is often shorter than the causative opioid's, especially long-acting opioids like methadone or buprenorphine — monitor for at least 4-6 hours after the last dose and always call emergency medical services. Offer a take-home naloxone kit and training to every patient with OUD, their household/support contacts, and anyone at risk of witnessing an overdose; kits are available at no cost through provincial take-home naloxone programs without a prescription.<cite data-reference-id="3a70ae74-aa01-459e-9f0c-b8699b47f89e"></cite> |
| Naltrexone | Adults: 50 mg PO once daily; observed ingestion preferred given adherence challenges Children: Not established for opioid use disorder — pediatric/adolescent OUD requires a specialized addiction pediatrics referral | Hepatotoxicity (dose-related), precipitated withdrawal if opioids are still active, nausea, headache | Special-situation alternative for patients who decline or are not on standard opioid agonist therapy and have already withdrawn from opioids. Requires confirmed opioid abstinence (about 7-10 days, longer after methadone) before starting, to avoid precipitating severe withdrawal. Injectable extended-release naltrexone is not currently available in Canada. |
Alpha2-Adrenergic Agonist
Symptomatic adjunct only — never a substitute for opioid agonist therapy.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Clonidine | Adults: 0.1-0.2 mg PO every 4-6 hours PRN, generally for less than 2 weeks Children: Not established for routine use in pediatric opioid withdrawal — specialist-directed only | Sedation, dry mouth, orthostatic hypotension, rebound hypertension if stopped abruptly | Blunts noradrenergic withdrawal symptoms (sweating, chills, flushing) but does not relieve myalgia, GI symptoms, or cravings. Hold if blood pressure is below about 85/55 mmHg; taper rather than stop abruptly after prolonged use. Use with caution in patients with cardiac disease or hypertension. |
Symptomatic Withdrawal Adjuncts
For breakthrough nausea, diarrhea, and myalgia during induction or withdrawal — adjuncts only, not treatment for the underlying disorder.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Dimenhydrinate | Adults: 50-100 mg PO every 4-6 hours PRN, maximum 400 mg/day | Sedation, dry mouth, blurred vision | For nausea during induction/withdrawal. |
| Loperamide | Adults: 4 mg PO after the first loose stool, then 2 mg after each subsequent loose stool, maximum 16 mg/day | Constipation, abdominal cramping; rare QT prolongation with supratherapeutic misuse | For diarrhea during withdrawal. Counsel explicitly against taking more than the labelled maximum. |
| Ibuprofen | Adults: 400 mg PO every 6-8 hours PRN with food | GI upset; renal effects with prolonged high-dose use | For bone/joint aches and myalgia during withdrawal. |
| Acetaminophen | Adults: 500-1000 mg PO every 4-6 hours PRN, maximum 4000 mg/day short-term with no hepatic risk factors | Hepatotoxicity at supratherapeutic doses | Alternative/adjunct analgesic for withdrawal-related myalgia when an NSAID is not appropriate. |
References
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) — American Psychiatric Association Publishing. Washington, DC: American Psychiatric Association Publishing; 2022
- Management of opioid use disorder: 2024 update to the national clinical practice guideline — CMAJ (Yakovenko I, Mukaneza Y, Germé K, et al.; Canadian Research Initiative in Substance Matters). CMAJ 2024;196(38):E1280-E1290
- The Clinical Opiate Withdrawal Scale (COWS) — Journal of Psychoactive Drugs (Wesson DR, Ling W). J Psychoactive Drugs 2003;35(2):253-259
- A Guideline for the Clinical Management of Opioid Use Disorder: 2023 Update — British Columbia Centre on Substance Use / BC Ministry of Health. Vancouver: BC Centre on Substance Use; 2023
- Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method — Substance Abuse and Rehabilitation (Hämmig R, Kemter A, Strasser J, et al.). Subst Abuse Rehabil 2016;7:99-105
- Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria — Addiction (McDonald R, Strang J). Addiction 2016;111(7):1177-1187
- Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding — Journal of Obstetrics and Gynaecology Canada (Turner S, Allen VM, Carson G, et al.; Society of Obstetricians and Gynaecologists of Canada). J Obstet Gynaecol Can 2023;45(11):102144
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.