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.
It is standard of care for prescribers to routinely reassess chronic opioid therapy (COT) with full mu agonists and consider alternative strategies as part of a comprehensive pain management plan. 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 [22, 23]. Buprenorphine has a unique pharmacologic profile as a partial agonist at the mu opioid receptor, which allows it to provide potent analgesia while potentially reducing 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 both patient and community safety [11].
This guideline will help providers identify appropriate candidates for transitioning from full mu COT to buprenorphine. The decision to transition to buprenorphine from other opioids should be a shared decision between patients and providers. This guideline does not provide a comprehensive 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.
The guideline covers:
Basics of Buprenorphine Cross-Titration
- What is buprenorphine?
- What are the advantages of buprenorphine?
- What are the disadvantages of buprenorphine?
- Who is a good candidate for cross-titration?
- Why should I use a cross-titration?
- What are the steps to a successful cross-titration?
Buprenorphine Cross-Titration Tables
Frequently asked questions
- What are common patient concerns?
- How to treat special populations (OUD, elderly, pregnancy, liver or kidney impairment)?
- What are the federal regulations for prescribing buprenorphine?
Appendix
- 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 [24].
- It is an effective analgesic while having a ceiling effect on respiratory depression, making it less likely to cause hypercarbic respiratory arrest [1,2,3,13].
- Buprenorphine has a longer half-life than short acting opioid medications (citation)
- Though it is more potent than morphine, there is no direct conversion to morphine equivalent doses due to its unique mechanism of action [4].
- 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. [5]
- Buprenorphine is available in various formulations, including sublingual tablets, sublingual films, buccal films, transdermal patches, and short and long-acting injectable formulations [2]. 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 [5].
- Buprenorphine has a lower risk of misuse, harm with diversion, and overdose compared to full mu opioid agonists [1,2,3].
- Buprenorphine may have fewer undesirable side effects associated with other opioids such as constipation, mood liability, immunosuppression, and respiratory depression (citation).
- 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 [22,23].
- Due to buprenorphine’s longer half-life, patients may have fewer pain flares between doses
- If your patients has an undiagnosed opioid use disorder and combines illicit opioids with buprenorphine, it may protect your patient from an overdose [25?, 27].
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 [21].
- Buprenorphine has a high binding affinity for the mu opioid receptor making reversal with naloxone less effective [26].
- 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. [7]
- Precipitated opioid withdrawal can occur if buprenorphine displaces full mu opioid agonists too quickly (15, 16). 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 [26].
- Patients on chronic opioid therapy (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 morphine equivalent dose (MED)
- Patients with psychological comorbidities (such as substance/alcohol use disorder, depression, and PTSD)[cite]
- 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 like heights or around machinery.
- A buprenorphine cross-titration allows patients to begin treatment with buprenorphine without going into opioid withdrawal. Patients are slowly tapered down on their full mu opioid agonist while simultaneously starting small, increasing doses of buprenorphine.
- Using small doses of buprenorphine that are titrated up over time avoids a large/sudden displacement of full mu agonist that can lead to precipitated opioid withdrawal. See the appendix – Diagnosing and Treating Precipitated Opioid Withdrawal .
- See Flowchart for detailed instructions.
- After determining your patient is an appropriate candidate, provide education on buprenorphine and address any patient concerns.
- Complete urine toxicology, a controlled substance agreement, and check the prescription drug monitoring program.
- Verify the patient’s MED to guide their target dose and formulation of buprenorphine.
- Determine the pace of each step of the transition (daily, weekly, monthly, etc). A slower, more gradual approach may be preferred for patients who need time to build confidence and understanding about the switch. A more rapid transition may be necessary for patients with safety concerns.
- After starting the cross-titration monitor for side effects, consider adjunctive therapies, and adjust the target dose if needed.
Flowchart
Key points
Use shared decision-making throughout the titration process to determine if the transition should be sped up or slowed down and to determine the ultimate buprenorphine dose.
Although doses and transitions should be tailored to fit patient and provider needs, providers 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. When considering sublingual films or sublingual tablets, either formulation would be considered first line.
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 | |
|---|---|
| < 30 MED | 75 mcg daily or twice daily |
| 30 – 89 MED | 150 mcg twice daily |
| 90 – 200 MED | 300 mcg twice daily |
| > 200 MED | Buprenorphine buccal film may not provide adequate analgesia |
| Timeline | Frequency / Dose | Full Mu Agonist |
|---|---|---|
| Step 1 | Initial dose | Reduce regimen by 20 – 30% |
| Step 2 | Increase step wise with next dosage, if needed | Reduce regimen by 20 – 30% |
| Step 3 | Increase step wise with next dosage, if needed | Reduce regimen by 20 – 30% |
| Step 4 | Increase step wise with next dosage, if needed | Reduce regimen by 20 – 30% |
| Step 5 | Increase step wise with next dosage, if needed | Discontinue |
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 to reach target dose | 2 mg/day | Reduce regimen by 20 – 30% |
| Step 4 | 1/2 film three times daily or variation to reach target dose | 3 mg/day | Reduce regimen by 20 – 30% |
| Step 5 | 1 film twice daily or variation to reach target dose | 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 to reach target dose | 3 mg/day | Reduce regimen by 20 – 30% |
| Step 4 | 1 film twice daily or variation to reach target dose | 4 mg/day | Reduce regimen by 20 – 30% |
| Step 5 | 1 film three times daily or variation to reach target dose | 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 to reach target dose | 3 mg/day | Reduce regimen by 20 – 30% |
| Step 4 | 1 film three times daily or variation to reach target dose | 6 mg/day | Reduce regimen by 20 – 30% |
| Step 5 | 2 film every morning, 1 film every afternoon and 1 film every evening or variation to reach target dose | 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.
- 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 [2,3,10].
- Patients may have concerns about the effectiveness of buprenorphine for pain relief compared to full mu opioid agonists. Studies show that buprenorphine is equianalgesic to morphine [Becca’s citations]. Transitioning to buprenorphine may lead to better safety [6,9,11,12,13]. 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 (15,16). 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. 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 [2].
- 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 [2].
- 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 [14].
- There are no federal restrictions on prescribing buprenorphine for chronic pain management outside of a standard DEA License [14].
- Buprenorphine is a schedule III controlled substance. Providers should still 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 [14, https://www.deadiversion.usdoj.gov/drug_chem_info/buprenorphine.pdf].
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
HMC Improving Addiction Care Team (IMPACT) Lead
OHSU/HMC
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
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://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm
- A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain– Gudin J, Fudin J. – Pain Ther. 2020 Jun;9(1):41-54. doi: 10.1007/s40122-019-00143-6. Epub 2020 Jan 28. PMID: 31994020; PMCID: PMC7203271.
- The Use of Opioids in the Management of Chronic Pain: Synopsis of the 2022 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline– Sandbrink, F., Murphy, J. L., Johansson, M., Olson, J. L., Edens, E., Clinton-Lont, J., Sall, J., Spevak, C., & VA/DoD Guideline Development Group. (2023). Annals of Internal Medicine, 176(3).
- Rethinking Opioid Dose Tapering, Prescription Opioid Dependence, and Indications for Buprenorphine– Chou, R., Ballantyne, J., & Lembke, A. (2019). Annals of Internal Medicine, 171(6), 427-429.
- CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022– Recommendations and Reports / November 4, 2022 / 71(3);1–95 – Deborah Dowell, MD; Kathleen R. Ragan, MSPH; Christopher M. Jones, PharmD, DrPH; Grant T. Baldwin, PhD; Roger Chou, MD
- Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. Accessed 8/14/2024.
- Buprenorphine Initiation Strategies for Opioid Use Disorder and Pain Management: A Systematic Review– Lauren A. Spreen, Emma N. Dittmar, Kyle C. Quirk, Michael A. Smith – First published: 18 March 2022
- FDA Warns about Dental Problems with Buprenorphine Medicines Dissolved in the Mouth to Treat Opioid Use Disorder and Pain– FDA Drug Safety Communication, January 12, 2022.
- The Conundrum of Opioid Tapering in Long-Term Opioid Therapy for Chronic Pain: A Commentary– Ajay Manhapra, MD, Albert A. Arias, MD and Jane C. Ballantyne, MD, Subst Abuse. 2018; 39(2): 152–161, PMCID: PMC6129223, NIHMSID: NIHMS1501568
- A Practical Guide for Buprenorphine Initiation in the Primary Care Setting– León-Barriera, R., Zwiebel, S. J., Johansson, M., Olson, J. L., Edens, E., Clinton-Lont, J., Sall, J., & Spevak, C. (2023). Cleveland Clinic Journal of Medicine, 90(8).
- Buprenorphine Microdose Induction for the Management of Prescription Opioid Dependence– Robbins, J. L., Englander, H., & Gregg, J. (2021). The Journal of the American Board of Family Medicine, 34(Supplement), S141-S146.
- Evaluation of Buprenorphine Rotation in Patients Receiving Long-term Opioids for Chronic Pain: A Systematic Review– Powell, V. D., Rosenberg, J. M., Yaganti, A., Garpestad, C., Lagisetty, P., Shannon, C., & Silveira, M. J. (2021). JAMA Network Open, 4(9):e2124152.
- Outpatient Cross-Titration to Buprenorphine for Chronic Pain: A Retrospective Analysis– Ito, S., Welsh, M., Bockman, C., Dale, R., Pilkington, D., & Peperzak, K. (2023). Journal of Opioid Management, 19(3).
- The Clinical Analgesic Efficacy of Buprenorphine– R. B. Raffa PhD, M. Haidery PharmD, H.-M. Huang PharmD, K. Kalladeen PharmD, D. E. Lockstein PharmD, H. Ono PharmD, M. J. Shope, PharmD – First published: 29 July 2014.
- Removal of DATA Waiver (X-Waiver) Requirement. SAMHSA, 29 July 2024.
- Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl– Varshneya NB, Thakrar AP, Hobelmann JG, Dunn KE, Huhn AS. J Addict Med. 2022 Jul-Aug 01;16(4):e265-e268. doi: 10.1097/ACM.0000000000000922. Epub 2021 Nov 23. PMID: 34816821; PMCID: PMC9124721.
- Withdrawal During Outpatient Low Dose Buprenorphine Initiation in People Who use Fentanyl: A Retrospective Cohort Study– Jones BLH, Geier M, Neuhaus J, Coffin PO, Snyder HR, Soran CS, Knight KR, Suen LW. Harm Reduct J. 2024 Apr 9;21(1):80. doi: 10.1186/s12954-024-00998-9. PMID: 38594721; PMCID: PMC11005253.
- Delphi Study to Explore a New Diagnosis for “Ineffective” Long-Term Opioid Therapy for Chronic Pain– Sara N Edmond, Jennifer L Snow 1, Jamie Pomeranz, Raymond Van Cleve, Anne C Black, Peggy Compton , William C Becker – PMID: 36448976 DOI: 10.1097/pain.0000000000002783
- Prescription Opioid Use Disorder Among Adults Reporting Prescription Opioid Use With or Without Misuse in the United States– Beth Han, MD, PhD, MPH; Christopher M. Jones, PharmD, DrPH, MPH; Emily B. Einstein, PhD; Deborah Dowell, MD, MPH; and Wilson M. Compton, MD, MPE
- Opioid Dependence vs Addiction: A Distinction Without a Difference?Ballantyne JC, Sullivan MD, Kolodny A., Arch Intern Med 2012;172(17):1342-3. doi: 10.1001/archinternmed.2012.3212.
- Complex Persistent Opioid Dependence with Long-term Opioids: a Gray Area That Needs Definition, Better Understanding, Treatment Guidance, and Policy Changes. Manhapra A, Sullivan MD, Ballantyne JC, MacLean RR, Becker WC. J Gen Intern Med. 2020 Dec;35(Suppl 3):964-971. doi: 10.1007/s11606-020-06251-w. Epub 2020 Nov 6. PMID: 33159241; PMCID: PMC7728942.
- Buprenorphine: A Treatment and Cause of Opioid-induced Respiratory Depression. Dahan, Albert et al. British Journal of Anaesthesia, Volume 128, Issue 3, 402 – 404.
- Oliva EM. Et al. Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation. BMJ. 2020 . doi: 10.1136/bmj.m283.
- Larochelle MR, et al. Comparative Effectiveness of Opioid Tapering or Abrupt Discontinuation vs No Dosage Change for Opioid Overdose or Suicide for Patients Receiving Stable Long-term Opioid Therapy. JAMA Netw Open. 2022 PMID: 35960518
- Conibear AE, Kelly E. A Biased View of μ-Opioid Receptors? Mol Pharmacol. 2019 Nov;96(5):542-549. doi: 10.1124/mol.119.115956. Epub 2019 Jun 7. PMID: 31175184; PMCID: PMC6784500.
- https://www.deadiversion.usdoj.gov/drug_chem_info/buprenorphine.pdf
- Naloxone reversal of buprenorphine-induced respiratory depression https://pubmed.ncbi.nlm.nih.gov/16809994
- Larochelle MR, Bernson D, Land T, Stopka TJ, Wang N, Xuan Z, Bagley SM, Liebschutz JM, Walley AY. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Ann Intern Med. 2018 Aug 7;169(3):137-145. doi: 10.7326/M17-3107. Epub 2018 Jun 19. PMID: 29913516; PMCID: PMC6387681.
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. [15, 16].
- Patients undergoing cross-titrations onto buprenorphine from prescription full agonist opioids (i.e., oxycodone, hydromorphone) are very unlikely to experience true POW because we are slowly displacing the full mu agonist. 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 [15, 16].
- 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 providers 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 |