What is the proper protocol for buprenorphine (opioid partial agonist) induction in a patient with opioid use disorder?

Buprenorphine Induction Protocol for Opioid Use Disorder

Buprenorphine induction requires patients to be in active opioid withdrawal (COWS score >8) before administration to prevent precipitated withdrawal, with initial dosing of 4-8 mg sublingual on Day 1, followed by 16 mg on Day 2, which becomes the standard maintenance dose for most patients. 1, 2

Pre-Induction Assessment and Timing

Confirm Active Withdrawal

• Use the Clinical Opiate Withdrawal Scale (COWS) and only administer buprenorphine when the score is >8 (moderate to severe withdrawal). 1
• Objective signs of withdrawal must be present—do not rely solely on patient report. 2

Required Waiting Periods Based on Last Opioid Use

The timing depends critically on the type of opioid used: 1, 2

• Short-acting opioids (heroin, oxycodone, hydrocodone): Wait minimum 12 hours, preferably not less than 4 hours after last use when clear withdrawal signs appear 1, 2
• Extended-release formulations: Wait >24 hours 1
• Methadone maintenance patients: Wait >72 hours (this is critical—methadone's long half-life creates high risk for severe precipitated withdrawal if buprenorphine is given too early) 1, 2

Special Consideration for Methadone Patients

Patients on methadone doses >30 mg are particularly susceptible to precipitated and prolonged withdrawal. 2 The 72-hour waiting period is essential because methadone's half-life can reach 30 hours, and premature buprenorphine administration will displace methadone from opioid receptors, causing severe withdrawal. 1 For methadone-maintained patients, consider continuing methadone for withdrawal management rather than switching to buprenorphine, as both have similar effectiveness. 1

Standard Induction Protocol (Day 1-2)

Day 1 Dosing

• Administer 4-8 mg sublingual buprenorphine based on withdrawal severity when COWS >8. 1, 2
• The dose may be given in 2-4 mg increments if preferred. 2
• Reassess after 30-60 minutes. 1
• Give additional 2-4 mg doses at 2-hour intervals if withdrawal symptoms persist. 1
• Target Day 1 total dose: 8 mg (though range of 4-8 mg is acceptable). 1

Day 2 Dosing

• Administer 16 mg total dose on Day 2. 1, 2
• This becomes the standard maintenance dose for most patients. 1

Tablet Administration Technique

• Place tablets under the tongue until completely dissolved—do not cut, chew, or swallow. 2
• Advise patients not to eat or drink until tablets are fully dissolved. 2
• For doses requiring more than two tablets, place all at once or two at a time under the tongue. 2

Maintenance Dosing (Day 3 Onward)

• The recommended maintenance dose is 16 mg daily for most patients, with a range of 4-24 mg depending on individual response. 1, 2
• Adjust dosage in 2-4 mg increments to suppress withdrawal and retain patients in treatment. 2
• Doses higher than 24 mg have not demonstrated clinical advantage. 2
• Switch to buprenorphine/naloxone combination products after induction to reduce diversion risk during unsupervised administration. 2

Managing Precipitated Withdrawal

If buprenorphine precipitates withdrawal despite proper timing:

Primary Treatment

• Give more buprenorphine—this is the most effective treatment for precipitated withdrawal. 1
• Buprenorphine's high receptor affinity means additional doses will eventually saturate receptors and provide relief. 1

Adjunctive Symptomatic Management

• Clonidine for autonomic symptoms (tachycardia, hypertension, sweating)—average 1.6 tablets needed per patient 3, 1
• Antiemetics (promethazine or ondansetron) for nausea/vomiting 3, 1
• Benzodiazepines for anxiety and muscle cramps 3, 1
• Loperamide for diarrhea 3, 1

Alternative Approach: Low-Dose (Micro-Dose) Induction

For patients who cannot tolerate standard induction (e.g., those on high-dose methadone, concurrent pain requiring opioids, or fentanyl users):

• Low-dose induction involves starting very low doses of buprenorphine (often IV) at fixed intervals with gradual increases while patients continue full agonist opioids. 4
• This approach avoids precipitated withdrawal and allows transition without stopping opioids. 5, 6, 4
• Success rates of 90.9% have been reported with stable pain and withdrawal scores. 4
• This is particularly useful for hospitalized patients with concurrent pain management needs. 5, 4

Discharge Planning and Harm Reduction

Prescribing

• Prescribe buprenorphine/naloxone 16 mg sublingual daily for 3-7 days or until follow-up. 1
• As of 2023, the X-waiver requirement has been eliminated, expanding prescribing access. 1
• Non-waivered providers can administer (but not prescribe) buprenorphine for up to 72 hours while arranging referral. 1

Essential Discharge Components

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

Critical Pitfalls to Avoid

1. Never administer buprenorphine to patients not in active withdrawal—this is the most common cause of precipitated withdrawal. 1, 2

2. Do not underestimate the waiting period for methadone patients—the 72-hour minimum is not negotiable. 1, 2

3. Do not discontinue buprenorphine once started—discontinuation precipitates withdrawal and dramatically increases relapse risk to more dangerous opioids. 7, 8

4. Avoid early provision of multiple refills—prescribe conservatively until patient stability is established. 2

5. Do not taper buprenorphine to comply with opioid dose guidelines—buprenorphine for OUD should not be reduced or discontinued as it has a ceiling effect on respiratory depression and is safer than full agonists. 7

Duration of Treatment

• There is no maximum recommended duration of maintenance treatment—patients may require treatment indefinitely. 2
• Continue buprenorphine as long as patients are benefiting and treatment goals are being met. 2
• Most patients with OUD who are tapered from buprenorphine relapse to more dangerous opioids. 7