Special features of buprenorphine

  • 24-72 half life, but probably 6-12hr analgesic half life
  • Partial mu/delta agonist, full kappa antagonist. Anti-hyperalgesic.
  • Low risk of significant respiratory suppression
  • Reduced hormonal effects and immunosuppression
  • Reduced immunosuppression 
  • Very high binding affinity: Possible “blocking effect” on other opioids at high buprenorphine doses, reducing euphoria or effects of other opioids used concurrently, which is helpful in opioid use disorder treatment. However, it theoretically may also complicate end of life care or perioperative care.  
  • Reduced GI side effects (esp: transdermal)
  • May use when NPO
  • Hepatic metabolism, may use in renal failure/ dialysis

Clinical Use: 

Buprenorphine efficacy for pain: 

  • Buprenorphine appears equivalent to morphine for acute pain states in multiple studies and using multiple routes. 
  • In patients chronically on and tolerant to opioids for chronic pain, rotation to buprenorphine has been shown to improve pain control in ~70% of patients. 
  • The equianalgesic conversion: 1mg bioavailable buprenorphine ~ 75mg oral morphine is somewhat controversial
  • When used for pain, dose BID to QID, or use continuous release patch. 
  • Some patients find buprenorphine without naloxone more analgesic, and some find the combination product more analgesic; use the formulation the patient prefers or that is more affordable.

Formulations and Dosing:

  • Butrans™: Pain indication. 5/7.5/10/15/20mcg/hr doses, and may prescribe up to two 20mcg patches concurrently. 5mcg/hr Butrans™ is equivalent to 9-13 OME/day, depending on equianalgesic calculation used. Can be used for opioid naïve patients at lowest dose. Can be started in patients without a “withdrawal day” period from short-acting opioids, though with caution that some precipitated withdrawal is possible. Skin irritation at the site of placement common.
  • Belbuca™ buccal film: Pain indication, approved for use 1 or 2x/day. Doses available are 75/150, 300/450/600/900mcg films. 75mcg = 3 OME. Would generally recommend 12-24 hrs of withdrawal from short-acting full agonist to avoid precipitated withdrawal, though may not be necessary if pre-conversion dose is low. Does not require X-number. Hardest formulation to get through insurance. 
  • Subutex™ SL tablet, buprenorphine only. Available in 2mg/8mg doses. OUD indication. May cause precipitated withdrawal, generally use withdrawal day type induction. 1mg = 15-30 OME. May be prescribed for OUD from clinic if provider has X-number, and appropriate resources, or without X-number off-label for pain (if pharmacy will fill this way).
  • Suboxone™, SL tab or film, buprenorphine and naloxone. OUD indication, off label for pain. Available in 2/4/8/12mg buprenorphine doses. Film is slightly more bioavailable than tablet. Typically withdrawal day start, but microdosing an option. 
  • Buprenex™ (buprenorphine hydrochloride) IV solution. Concentration is 0.3mg/ml, in single use 1ml ampules. 1 vial (0.3mg) is ~22 OME. As of 2020, not included in UCSF formulary.

Types of Inductions for Patients Converting from Other Opioids to Buprenorphine:

Withdrawal-type induction: 

  • Hold methadone 3-7d, intermediate acting opioids (oxycodone SR, morphine SR) for 2-4d, hold short-acting opioids 12-24hr or until COWS Scale Score >8 before providing initial 1-2mg buprenorphine.

Microdosing-type induction:

  • Do not hold other opioids or wait for obvious signs or symptoms of withdrawal. Start with ¼ of a 2mg tablet, and repeat q1-2 hours. 
  • OR, place a butrans patch (ok to place at highest dose and still continue other opioid therapy if indicated) 12-48 hours prior to intended sublingual buprenorphine dose start, and then induce starting at ½ or 1 full 2mg tablet or film. 
  • In either case, treat withdrawal symptoms, if present, with alpha-2-agonists, anti-emetics, anti-spasmodics, and anxiolytics if needed. Ketamine may also be helpful.

Special Considerations:

  • May prolong QTc (but much less than methadone)
  • May cause precipitated withdrawal if given while other opioids still circulating
  • Will not show up as “opioid” on a typical point of care drug, but detectable on GCMS confirmatory test. 
  • Rarely causes transient or lasting LFT elevations, which resolve with dose reduction. 
  • May lower seizure threshold.
  • Typical opioid side effects possible: sedation, nausea, pruritus, dizziness, constipation, development of dependency/tolerance, driving impairment
  • As with all opioids, when starting buprenorphine in an opioid naïve patient, or when rotating from another opioid, use a more conservative estimate of expected dose need, and consider reducing the expected target dose by 10-50% for reduced cross-tolerance in opioid rotation.

DEA Scheduling:

  • All formulations are DEA Schedule III. May be prescribed by phone or fax, in addition to e-prescription and on barcode-printed prescription paper. Refills may be provided on a prescription. 
  • Buprenorphine be used for clinic-based opioid use disorder (OUD) treatment (but only Subutex™, Suboxone™, Zubsolv™, or Bunavail™), with a DEA assigned X-number. 
  • Theoretically, all formulations, whether indicated for pain or OUD, may be prescribed for pain, though prescription of OUD-indicated formulations for pain can be complicated by EMR limitations, insurance, and pharmacies if provider does not have an X-number.

White. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2018

Pergolizzi. Current Knowledge of Buprenorphine and Its Unique Pharmacological Profile. Pain Practice. 2010

Pergolizzi. Safety And Efficacy Of The Unique Opioid Buprenorphine For The Treatment Of Chronic Pain. J Pain Res. 2019

Tang. Case Series: Limited Opioid Withdrawal With Use of Transdermal Buprenorphine to Bridge to Sublingual Buprenorphine in Hospitalized Patients. Am J Addict. 2020