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Practice Guide for Clinicians: Buprenorphine

Practice guide for transitioning patients from full mu chronic opioid therapy to buprenorphine for chronic pain

Authors: Eleasa Sokolski MD, Christina Bockman PharmD, Jacob Gross MD MPH, Mark Stephens BS, Rebecca Dale DO

Target audience

Clinicians who are prescribing for and managing patients on full mu opioid agonists for chronic pain.

Scope

This guide provides clinicians with evidence-based strategies and model protocols for transitioning patients from full mu opioid agonist therapy to buprenorphine for chronic pain management.

Introduction

Effective chronic pain management requires ongoing reassessment of full mu chronic opioid therapy (COT) and consideration of alternative strategies to minimize risk, including opioid reduction. However, not all patients tolerate tapering off full mu opioid agonists, and abrupt discontinuation or forced tapering in certain populations has been shown to have adverse outcomes.1,2 Buprenorphine, with its unique pharmacologic profile as a partial agonist at the mu opioid receptor and kappa antagonist, offers potent analgesia while potentially reducing the risks associated with full mu COT. For patients on full mu COT, cross-titration to buprenorphine can significantly enhance well-being, improve pain management, and increase patient safety.3 However, there is little guidance on how to transition patients from full mu COT to buprenorphine.

This practice guide will help clinicians identify appropriate candidates for transitioning from full mu COT to buprenorphine. Buprenorphine, like all opioid therapy, may not be an appropriate or effective medication for all patients. Buprenorphine is not a replacement for a comprehensive, biopsychosocial treatment strategy for chronic pain. This guide does not provide an overview of opioid use disorder (OUD) treatment.

These recommendations are intended as an educational reference. While buprenorphine can be an effective and safer alternative to full mu COT, it requires careful management and consideration of individual patient factors.

Disclaimer

This practice guide is for educational purposes only. While efforts have been made to ensure accuracy, the information presented does not establish a standard of care. Clinical decisions should be made by qualified healthcare clinicians based on individual patient circumstances. The authors and their institutions assume no liability for any outcomes related to the use of this guide.

  • A buprenorphine cross-titration allows patients to begin treatment with buprenorphine without going into opioid withdrawal.4-6 Patients are slowly tapered down on their full mu opioid agonist while simultaneously starting small, increasing doses of buprenorphine.
  • This strategy avoids a large/sudden displacement of full mu opioid agonist that can lead to precipitated opioid withdrawal. See the appendix – Diagnosing and Treating Precipitated Opioid Withdrawal.
  • See Buprenorphine Cross-Titration Flowchart for steps to a successful cross-titration.
  • See Select Buprenorphine Formulations Table to select an appropriate formulation.

Table of Select buprenorphine formulations

*Contains naloxone which is used to deter misuse of the buprenorphine product. When administered correctly naloxone is not readily bioavailable and therefore should not block or reverse opioid activity

**Available as generic buprenorphine only

  • These tables serve as examples. Doses and transitions should be tailored to fit patient and clinician needs. A slower, more gradual approach may be preferred for patients who need time to build confidence and understand more about the switch. A more rapid transition may be necessary for patients with safety concerns.
  • Clinicians should avoid escalating buprenorphine significantly beyond target doses without further evaluation of underlying pain conditions and/or comorbidities, such as re-evaluation for OUD.
  • Insurance may prefer certain buprenorphine formulations. Many formulations could be considered first line. Please note that some formulations are considered off-label for pain management.

 

Maximum dose = 20 mcg/hr every 7 days
MED < 60

Timeline Frequency / Dose Full Mu Agonist
Step 1 5 mcg/hr Reduce regimen by 20 – 30%
Step 2 7.5 mcg/hr Reduce regimen by 20 – 30%
Step 3 10 mcg/hr (stop here if MED < 30) Reduce regimen by 20 – 30%
Step 4 15 mcg/hr Reduce regimen by 20 – 30%
Step 5 20 mcg/hr Discontinue

Maximum dose = 900mcg every 12 hours (1800 mcg/day)
MED < 200
Target Dose 300 – 1800 mcg/day

Timeline Frequency / Dose Full Mu Agonist
Step 1 150 mcg twice daily Reduce regimen by 20 – 30%
Step 2 300 mcg twice daily Reduce regimen by 20 – 30%
Step 3 450 mcg twice daily (stop here if MED < 90) Reduce regimen by 20 – 30%
Step 4 600 mcg twice daily Reduce regimen by 20 – 30%
Step 5 750 mcg twice daily (increase to next dosage, if needed) Discontinue
Step 6 900 mcg twice daily

Based on Buprenorphine/Naloxone 2 mg/0.5 mg film product

MED < 200

Target Dose 2 – 4 mg/day

Timeline Frequency Daily Dose Full Mu Agonist
Step 1 1/4 film twice daily 1 mg/day Reduce regimen by 20 – 30%
Step 2 1/4 film three times daily 1.5 mg/day Reduce regimen by 20 – 30%
Step 3 1/2 film twice daily or variation (stop here if MED < 90) 2 mg/day Reduce regimen by 20 – 30%
Step 4 1/2 film three times daily or variation 3 mg/day Reduce regimen by 20 – 30%
Step 5 1 film twice daily or variation 4 mg/day Discontinue

 

MED 200 – 400 

Target Dose 4 – 6 mg/day

Timeline Frequency Daily Dose Full Mu Agonist
Step 1 1/4 film twice daily 1 mg/day Reduce regimen by 20 – 30%
Step 2 1/4 film three times daily 1.5 mg/day Reduce regimen by 20 – 30%
Step 3 1/2 film three times daily or variation 3 mg/day Reduce regimen by 20 – 30%
Step 4 1 film twice daily or variation 4 mg/day Reduce regimen by 20 – 30%
Step 5 1 film three times daily or variation 6 mg/day Discontinue

 

MED > 400

Target Dose 6 – 8 mg/day

Timeline Frequency Daily Dose Full Mu Agonist
Step 1 1/4 film twice daily 1 mg/day Reduce regimen by 20 – 30%
Step 2 1/4 film three times daily 1.5 mg/day Reduce regimen by 20 – 30%
Step 3 1/2 film three times daily or variation 3 mg/day Reduce regimen by 20 – 30%
Step 4 1 film three times daily or variation 6 mg/day Reduce regimen by 20 – 30%
Step 5 2 films every morning, 1 film every afternoon, and 1 film every evening 8 mg/day Discontinue

Note: These tables have been adapted from Outpatient Cross-titration to Buprenorphine for Chronic Pain: A Retrospective Analysis. Ito S, Welsh M, Bockman C, Dale R, Pilkington D, Peperzak K. J. Opioid Manag. 2023 Nov-Dec; 19(6);543-554 and the bioavailability data in the Select Buprenorphine Formulations Table.

  • Buprenorphine is a semisynthetic opioid with complex receptor activity. It acts as a partial agonist at the mu opioid receptor with potent activation of analgesic pathways but only partial activation of respiratory depressant pathways. It also acts as an antagonist at the kappa-opioid receptor and has distinct actions at delta opioid receptors.12,13
  • It is an effective analgesic while having a ceiling effect on respiratory depression, making it less likely to cause hypercarbic respiratory arrest.12,14,15
  • Buprenorphine has a longer half-life than short acting opioid medications.16
  • Though it is more potent than morphine, there is no direct conversion to morphine equivalent doses.17
  • As with all opioids, buprenorphine’s side effects include nausea, constipation, headache, drowsiness, insomnia, diaphoresis, hypotension, hypertension and dizziness. Serious side effects can include respiratory depression and QTc prolongation.16 Transmucosal formulations can also cause dry mouth and an increased risk of dental problems.18
  • Buprenorphine is available in various formulations, including sublingual tablets, sublingual films, buccal films, transdermal patches, and short and long-acting injectable formulations.14,16 This variety in routes of administration provides flexible options for different patient needs. Some formulations are combined with naloxone to deter misuse and potential overdose if injected, as naloxone is only significantly bioavailable through the intravenous route.16
  • Buprenorphine has a lower risk of misuse, harm with diversion, and overdose compared to full mu opioid agonists.12,14,19
  • Buprenorphine may have fewer undesirable side effects associated with other opioids such as constipation, mood liability, immunosuppression, and respiratory depression.3,20
  • Replacement of full agonist COT in high-risk patients with buprenorphine may reduce the risk of suicidal ideation when compared to a taper or discontinuation.1,2
  • Due to buprenorphine’s longer half-life, patients may have fewer pain flares between doses.
  • If your patient has an undiagnosed opioid use disorder and combines illicit opioids with buprenorphine, it may protect your patient from an overdose.21
  • The variety of formulations offers options for patients with limited oral intake.
  • While buprenorphine is considered safer than other full mu opioid agonists, respiratory depression can still occur, especially when combined with alcohol and/or other sedative/hypnotics.22
  • Buprenorphine has a high binding affinity for the mu opioid receptor making reversal with naloxone less effective.23
  • Transmucosal formulations have an increased risk of dental problems and should not be chewed or swallowed. Patients should be educated to swish and swallow with a small sip of water 30 minutes after use and avoid brushing teeth at least 1 hour after administration of these products.18
  • Precipitated opioid withdrawal can occur if buprenorphine displaces full mu opioid agonists too quickly.3,17,24 Careful initiation of buprenorphine is critical to ensure this does not occur. See the appendix – Diagnosing and Treating Precipitated Opioid Withdrawal .
  • Buprenorphine is a schedule III controlled substance, and there is potential for misuse and/or diversion of buprenorphine like other opioid medications.25
  • Patients on full agonist COT who are at high risk for opioid-related harms and cannot or will not taper. High-risk patients include:
    • Patients prescribed greater than 50 MED26
    • Patients with psychological comorbidities (such as substance/alcohol use disorder, depression, and PTSD)
    • Patients with medical conditions (respiratory compromise, hepatic/renal insufficiency, and cognitive impairment)
  • Patients with inconsistent urine toxicology screens, requests for early refills or dose escalation, sedation, or declining function despite ongoing opioid therapy.
  • Patients on full agonist COT at risk for developing health complications that can worsen over time, such as chronic kidney disease, increased fall risk, or neurological conditions like Parkinson’s disease or stroke (example age >65).
  • Consider patients’ living situations and occupational risks, including those with unstable housing, those who don’t fully control their medications, and those who drive or work in high-risk environments, such as working up high or around machinery.
  • Patients may have concerns about taking a medication that is also used to treat OUD. Emphasize that buprenorphine is an FDA-approved and evidence-based treatment for chronic pain.14
  • Patients may have concerns about the effectiveness of buprenorphine for pain relief compared to full mu opioid agonists. Studies show that buprenorphine provides similar levels of analgesia to full mu COT, particularly when patients are maintained on a stable dose of buprenorphine.3,15 It can be helpful to frame a transition to buprenorphine as an opioid rotation with the goal of reducing negative effects of long-term full mu-agonist opioid therapy.
  • Some patients may worry about having opioid withdrawal when transitioning to buprenorphine. Withdrawal may occur either from the reduction of a full mu opioid agonist or the displacement of a full agonist at the mu opioid receptor by buprenorphine. See the appendix – Diagnosing and Treating Precipitated Opioid Withdrawal. Reassure patients that a gradual transition plan by cross-titration can minimize the risk of both types of withdrawal. Have a plan in place to manage withdrawal symptoms if they occur and review this plan with your patient.
  • Patients may be concerned about how acute pain will be managed while they are on buprenorphine. Provide reassurance that non-opioid and non-pharmacologic options will remain effective for the treatment of acute pain.27,28 Full mu opioid agonists may also be used, short term, in addition to buprenorphine, as deemed appropriate by a medical professional.
  • Patients with co-occurring chronic pain and OUD: While buprenorphine can effectively treat both chronic pain and OUD by managing cravings and withdrawal while reducing overdose risk, patients using non-prescribed opioids may require higher doses due to high opioid tolerance.
  • Elderly patients: Buprenorphine may be a safer option for older adults due to its lower risk of respiratory depression and fewer drug interactions compared to full opioid agonists. Start with lower doses and titrate slowly, monitoring for adverse effects.14
  • Pregnant patients: Any change to chronic opioid therapy during pregnancy should be made through shared decision making with the patient and with support of a clinical expert (obstetrician, pain specialist, addiction specialist).
  • Patients with liver or kidney impairment: Buprenorphine is metabolized primarily by the liver, so dose adjustments may be necessary for patients with severe hepatic impairment. No dose adjustments are needed for patients with renal impairment.14,16
  • There is insufficient evidence to recommend buprenorphine for the treatment of chronic pain in children and adolescents.
  • As of December 2022, the X-waiver requirement for prescribing buprenorphine for OUD has been eliminated.29
  • There are no federal restrictions on prescribing buprenorphine for chronic pain management outside of a standard DEA License.29
  • Buprenorphine is a schedule III controlled substance. Clinicians should adhere to state-specific regulations and best practices for prescribing controlled substances, such as checking prescription drug monitoring programs and conducting periodic urine drug screens.25,29

Eleasa Sokolski MD
Assistant Professor of Medicine and Psychiatry, OHSU Division of General Internal Medicine, Section of Addiction Medicine

Christina Bockman, PharmD
UW Medicine, Pain Management Clinical Pharmacist, Telepain and Opioid Clinical Pharmacist Specialist, Departments of Pain Medicine and Pharmacy Services

Jacob Gross MD MPH
UW Medicine, Assistant Professor, Department of Anesthesiology and Pain Medicine, Director UW Medicine Telepain

Mark Stephens BA
President – Change Management Consulting
Editor for the Northwest Pain Guidance website, developer of the Pain Education Toolkit

Rebecca Dale
VA Puget Sound and University of Washington
Associate Professor of Anesthesiology and Pain Medicine
Past Program Director for the UW Pain Medicine Fellowship
Board certification in chronic pain, addiction, and anesthesiology

Jane Ballantyne, MD, FRCA
Board certified anesthesiologist at UW Medical Center and a UW professor (retired) of Anesthesiology and Pain Medicine and Director of the UW Pain Fellowship

Dan Hoover, MD
Assistant Professor, OHSU Division of General Internal Medicine
Section of Addiction Medicine
Addiction Medicine Consult Service (IMPACT Team)
Addiction Medicine ECHO Director

Linda Peng, MD
Assistant Professor of Medicine
OHSU Hillsboro Medical Center Improving Addiction Care Team (IMPACT) Lead
OHSU Division of General Internal Medicine & Geriatrics, Section of Addiction Medicine

University of Washington TelePain Sessions

https://anesthesiology.uw.edu/what-we-do/pain-medicine/telepain/

Oregon ECHO Network

https://www.oregonechonetwork.org/addictionmed

Provider Clinical Support Services

http://www.pcssnow.org 
PCSS offers an 8-hour buprenorphine for OUD training, on-demand chronic pain curriculum, and mentoring support.

Morphine Equivalent Dose Calculator

This calculates the Morphine Equivalent Dose (MED) dose for a patient taking one or more opioid medications. The MED ratios are from the 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain.
https://northwestpainguidance.org/opioidmedcalculator/

Diagnosing and Treating Precipitated Opioid Withdrawal

  • Precipitated opioid withdrawal (POW) occurs when buprenorphine displaces full mu opioid agonists due to its higher binding affinity. Symptoms typically occur 30-60 minutes after a dose of buprenorphine and include nausea, vomiting, diarrhea, sweating, body aches, chills, and restlessness.24
  • Patients undergoing cross-titrations onto buprenorphine from prescription full agonist opioids (i.e., oxycodone, hydromorphone) are very unlikely to experience true POW because the full mu agonist is slowly being displaced. It is more common for patients to have mild opioid withdrawal symptoms due to dose reductions in their full agonist opioid.
  • Patients who use illicitly manufactured high-potency synthetic opioids (e.g., fentanyl) are at much higher risk of experiencing POW.24
  • If a patient has mild to moderate withdrawal symptoms after a step-down in their full agonist opioid, consider increasing buprenorphine by moving to the next step in the pathway.
  • If there is concern for true POW (clear symptom onset 30-60 minutes after taking buprenorphine), consider staying at the lower dose of buprenorphine for an additional 1-2 days before increasing.
  • Adjunctive medications can help alleviate symptoms of opioid withdrawal and POW [see table]. Consider prescribing adjuncts for patients who experience significant opioid withdrawal symptoms during the cross-titration and for those with prior history of POW.

The following adjuncts can be prescribed as indicated and appropriate. Note that these are STARTING DOSES and clinicians can prescribe more if needed.

Adjunctive Medication Dose Indication
Acetaminophen 500 mg every 6 hours as needed Mild to moderate pain
Clonidine 0.1 mg three times daily as needed Sweating, anxiety, restlessness, insomnia
Gabapentin 300 mg every 8 hours as needed Anxiety, restlessness, insomnia
Hydroxyzine 25 mg every 6 hours as needed Anxiety
Ibuprofen 400 mg every 6 hours as needed Mild to moderate pain
Loperamide 2 mg every 6 hours as needed Diarrhea
Melatonin 3 mg at bedtime as needed Insomnia
Ondansetron 4 mg every 8 hours as needed Nausea
Tizanidine 2 mg every 6 hours as needed Muscle spasms
  1. Oliva EM, Bowe T, Manhapra A, et al. Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation. Bmj. Mar 4 2020;368:m283. doi:10.1136/bmj.m283
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  5. Robbins JL, Englander H, Gregg J. Buprenorphine Microdose Induction for the Management of Prescription Opioid Dependence. J Am Board Fam Med. Feb 2021;34(Suppl):S141-s146. doi:10.3122/jabfm.2021.S1.200236
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  7. BioDelivery Sciences International, Inc. Belbuca (buprenorphine) [Package Insert]. US. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207932s023lbl.pdf#page=40 Revised December 2023. Accessed February 28, 2025.
  8. LTS Lohmann Therapy Systems Corp. Butrans (buprenorphine) [Package Insert]. US. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021306s041lbl.pdf#page=45 Revised April 2014. Accessed February 28, 2025.
  9. Indivior Inc. Suboxone (buprenorphine and naloxone) [Package Insert]. US. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022410s046s047lbl.pdf#page=35 Revised June 2022. Accessed February 28, 2025.
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