Background   This Fast Fact addresses analgesic management for patients taking buprenorphine for opioid use disorder (OUD).  Buprenorphine is a mixed opioid agonist/antagonist, available in the United States in the sublingual form as ‘Subutex,’ and formulated with naloxone as ‘Suboxone’ (and other brand names). Such use is restricted to qualified physicians, nurse practitioners, and physician assistants who have received training and a waiver (“X-waiver”) to prescribe buprenorphine for OUD.  Generalist clinicians are likely to encounter patients on buprenorphine therapy for OUD who also require treatment for pain.  Note:  buprenorphine is also approved in the US as an analgesic where it is available as an IV solution and a transdermal system (Butrans) (see Fast Fact #268).  When used for analgesia, only proper DEA registration for a controlled III substance is necessary to prescribe buprenorphine. In this Fast Fact‘buprenorphine’ refers to all sublingual (SL) products.

Pharmacology   Buprenorphine binds to mu-opioid receptors tightly but with low intrinsic activity, providing some analgesic effects but effectively preventing other opioids from binding.  This ‘blocks’ the analgesic and euphoric effects of other opioids, leading to its effectiveness in OUD.  Buprenorphine’s effect at the mu-opioid receptor lasts 24 to 60 hours and can be extended with increasing doses. However, the duration of SL buprenorphine’s analgesic effects is between 6 to 12 hours, which is much shorter than its occupation of the receptor. Naloxone has minimal SL bioavailability and is included in formulations only to prevent intravenous misuse (1).

Pain Management Strategies   In the past, there was concern that the interaction of buprenorphine with opioid receptors would limit the analgesic effectiveness of other opioids.While there are no well-powered, controlled trials addressing the effectiveness of opioid analgesia in patients taking buprenorphine for OUD, observational data and data from small trials suggests that buprenorphine at therapeutic doses does not impair the effectiveness of other opioids (2-5).  In fact, in one retrospective study, patients who stopped buprenorphine before surgery had higher opioid usage and rated their pain control worse than those who continued buprenorphine through the peri-operative period (6). Additionally, patients who stop their buprenorphine are at risk for withdrawal and opioid craving.  In the setting of a serious illness, patients are already experiencing stress that may endanger their addiction recovery, and OUD treatment should be prioritized.  Palliative care clinicians should work closely with addiction treatment specialists to develop integrated treatment plans. The following pain management strategies have been recommended by experts for patients taking buprenorphine for OUD (7-10): 

• Anticipate pain flares for scheduled medical interventions or procedures. Develop proactive analgesic plans involving non-opioid adjuvant analgesics and non-pharmacologic therapies such as nerve blocks when appropriate.
• When mild-to-moderate acute pain is anticipated for a short period of time (e.g., dental extraction), consider treating the pain with nonopioid analgesics such as NSAIDs.  The total daily dose of SL buprenorphine can be increased (to a maximum of 32 mg sublingual/day); it should be given in divided doses every 6-8 hours.   
• When moderate to severe pain is anticipated for a short period of time (e.g., major abdominal surgery), continue the buprenorphine and add short acting opioid agonists as needed for breakthrough pain.  The buprenorphine may be split into divided doses (two to four times per day).  Opioid dosing should account for the individual’s opioid tolerance. 
• Clinicians may encounter hospitalized patients for whom their outpatient buprenorphine has been discontinued, and other opioids started to manage pain.  For these patients, the timing of restarting buprenorphine will be based on patient preference and the clinical scenario.  Buprenorphine induction can cause precipitated withdrawal if patients have been receiving other opioids and should be managed by an experienced, waivered clinician.
• For patients with pain from an incurable, progressive illness, decisions about buprenorphine therapy should be based on an assessment of the patient’s history of OUD as well as their medical diagnoses and prognosis. Clinicians should encourage continued treatment with buprenorphine if possible, with the addition of other opioids for treatment of disease-related pain when non-opioid modalities are not sufficient. 
• If buprenorphine is ineffective for analgesia, rotation to methadone can be considered in select patients. However, since patients with OUD are at higher risk of opioid misuse, clinicians should be cautious with prescribing methadone for pain considering its complex pharmacodynamics. One option is for methadone to be provided through an opioid treatment program (a methadone clinic), rather than by a palliative care clinician. Additional opioids may then be provided for disease-related pain in collaboration with the methadone program. 
• A collaborative approach, including patient preference and discussion with both addiction and pain or palliative care specialists, will best identify a therapeutic plan to achieve adequate pain relief and maintain recovery from addiction.  

Author Affiliations:  University of Pittsburgh Medical Center, Pittsburgh, PA.

Conflicts of Interest: None

Version History: Originally published November 2009; re-edited in August 2015; re-edited again in December 2020.

References

1. Alford DP, et al.  Acute pain management for patients receiving maintenance methadone or buprenorphine therapy.  Ann Intern Med. 2006; 144:127-134.
2. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. Available at http://buprenorphine.samhsa.gov/Bup_Guidelines.pdf.  Accessed June 25, 2009.
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6. Kögel B, Christoph T, Strassburger W, Friderichs E.  Interaction of mu-opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice.  Eur J Pain. 2005; 9(5):599-611.
7. Macintyre PE, Russell RA, Usher KA, Gaughwin M, Huxtable CA.  Pain relief and opioid requirements in the first 24 hours after surgery in patients taking buprenorphine and methadone opioid substitution therapy.  Anaesth Intensive Care. 2013 Mar;41(2):222-30.
8. Mark, TL, Kassed CA, Vandivort-Warren R, et al.   Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty.  Drug Alcohol Depend. 2009; 99:345-349.
9. Mercadante S, Villari P, Ferrera P, et al.  Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine.  J Pain Symptom Manage. 2006; 32(2):175-9.
10. Schumacher MA, Basbaum AI, Way WL.  Opioid analgesics and antagonists.  In: Katzung BG, ed. Basic and clinical pharmacology.  New York, NY: McGraw-Hill; 2007.

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