What is the recommended Suboxone (buprenorphine/naloxone) induction protocol for a patient with moderate opioid withdrawal (COWS 8‑12) after 12‑24 hours for short‑acting or 24‑72 hours for long‑acting opioids since the last full‑agonist dose?

Suboxone Induction Protocol for Moderate Opioid Withdrawal

For a patient with moderate withdrawal (COWS 8–12) after appropriate waiting periods, initiate buprenorphine/naloxone with 4–8 mg sublingual, reassess after 30–60 minutes, and provide additional 2–4 mg doses every 2 hours as needed to target a Day 1 total of approximately 8 mg, followed by 16 mg daily maintenance starting Day 2. 1

Pre-Induction Requirements

Timing Verification

Before administering the first dose, confirm adequate time has elapsed since the last opioid use to prevent precipitated withdrawal: 1

• Short-acting opioids (heroin, immediate-release oxycodone/morphine, fentanyl): Wait >12 hours 1, 2
• Extended-release formulations (OxyContin, MS Contin): Wait >24 hours 1, 2
• Methadone maintenance: Wait >72 hours and strongly consider continuing methadone instead, as it has comparable effectiveness and avoids precipitated withdrawal risk 1, 3

Withdrawal Assessment

• Use the Clinical Opiate Withdrawal Scale (COWS) to objectively confirm moderate-to-severe withdrawal 1, 3
• Only administer buprenorphine when COWS ≥8; if COWS <8, defer dosing and reassess in 1–2 hours 1
• A COWS of 8–12 indicates moderate withdrawal and is the appropriate threshold for safe induction 1

Safety Screening

Before induction, screen for: 1

• QT-prolonging medications (contraindicated with buprenorphine)
• High-risk benzodiazepine co-prescribing (FDA black-box warning for respiratory depression and death)
• Pregnancy, acute intoxication, recent naloxone reversal, or serious acute medical illness

Day 1 Induction Protocol

Initial Dose

• Administer 4–8 mg sublingual buprenorphine/naloxone based on withdrawal severity 1, 3, 2
• For COWS 8–12 (moderate withdrawal), 4 mg is typically sufficient as the starting dose 1
• Place tablets under the tongue until completely dissolved; do not eat, drink, chew, or swallow 2

Reassessment and Additional Dosing

• Reassess COWS after 30–60 minutes 1, 3
• If withdrawal persists, provide additional 2–4 mg every 2 hours as needed 1, 3
• Target Day 1 total: approximately 8 mg (range 4–8 mg depending on response) 1, 3
• Rapid dose escalation on Day 1 reduces dropout rates compared to gradual multi-day induction 2

Day 2 and Maintenance Dosing

• Standard maintenance dose: 16 mg sublingual daily starting Day 2 1, 3, 2
• This dose occupies ~95% of mu-opioid receptors and creates a ceiling effect for both therapeutic benefit and respiratory depression 1
• Acceptable dose range: 4–24 mg daily, though most patients require 16 mg 1, 2
• Once-daily dosing is preferred; twice-daily dosing (e.g., 8 mg BID) increases respiratory risk when combined with benzodiazepines 1

Management of Precipitated Withdrawal

If precipitated withdrawal occurs despite following timing guidelines:

Primary Treatment

• Administer additional buprenorphine (not less) as the primary intervention 1, 3
• Give 2 mg every 1–2 hours; for severe precipitated withdrawal, escalate rapidly to 20 mg total if needed 3
• This approach is supported by pharmacologic rationale and case reports 1

Adjunctive Symptomatic Management

Provide targeted medications for specific symptoms: 1, 3

• Clonidine (0.1–0.2 mg every 6–8 hours) for autonomic symptoms (sweating, tachycardia, hypertension)
• Antiemetics (promethazine or ondansetron) for nausea and vomiting
• Benzodiazepines for anxiety and muscle cramps
• Loperamide (2–4 mg as needed) for diarrhea

Discharge Planning

Prescription

• Prescribe buprenorphine/naloxone 16 mg sublingual daily for 3–7 days or until the first follow-up appointment 1, 3
• No refills on the initial prescription 1
• As of 2023, the X-waiver requirement has been eliminated; any DEA-licensed provider can prescribe 1

Harm Reduction and Screening

• Provide a take-home naloxone kit and overdose-prevention education 1, 3
• Offer hepatitis C and HIV screening 1, 3
• Consider reproductive health counseling 1, 3

Common Pitfalls to Avoid

• Initiating buprenorphine when COWS <8 will precipitate severe withdrawal 1, 3
• Starting buprenorphine <72 hours after methadone leads to prolonged precipitated withdrawal 1
• Prescribing discharge doses below 16 mg daily often results in persistent withdrawal and treatment failure 1
• Gradual multi-day induction increases dropout rates; rapid dose escalation to 8 mg on Day 1 is preferred 2
• Abruptly discontinuing buprenorphine precipitates withdrawal and dramatically increases relapse risk to more dangerous opioids 1

Evidence Quality Note

The incidence of buprenorphine-precipitated withdrawal when proper timing and COWS thresholds are followed is low (0–13.2% across studies), and should not be a barrier to initiating this life-saving treatment. 4 Recent evidence demonstrates that extended-release formulations can be safely initiated even at lower COWS scores (4–7), though precipitated withdrawal risk increases at COWS 0–3. 5