Buprenorphine: the micro and (not so) micro factoids

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Rachel Rafeq
Emergency medicine pharmacist and toxicology enthusiast. Trained in medication safety and I apply that to everything. I love photography and world schooling my kids.

The Pre-brief

  • Over 2 million Americans struggle with opioid use disorder
  • In 2018, more than 67,000 lives were lost to overdose
  • Opioids accounted for ~70% of these deaths
  • More than 40 states have reported increased mortality from opioids during the COVID 19 pandemic
  • The opioid epidemic requires us to be proactive and progressive

Intro to Buprenorphine

  • One of three medications utilized in medication-assisted treatment of opioid use disorder
  • Buprenorphine’s pharmacology and safety profile make it an attractive choice and a safer option for medication
    assisted treatment in opioid use disorder compared to methadone
  • Mechanism of action: Partial µ-opioid agonist and ĸ-opioid antagonist
  • Compared to methadone:
    • Lower risk of overdose since it is a partial opioid agonist
    • “Ceiling effect”
    • Less drug interactions
    • Low risk for QT prolongation (<1% in post marketing data)
    • Lower abuse potential
    • Higher binding affinity to the opioid receptor
    • Highest binding to the opioid receptor than any
      other opioid. If an individual is using heroin and
      then takes buprenorphine, buprenorphine is
      capable of competitively inhibits heroin from binding to the opioid receptor and displaces
      already bound heroin at the receptor site.
    • Because it’s a partial agonist, it can precipitate a withdrawal
  • Withdrawal symptoms:
    • Sweating/chills
    • Tremors/anxiety
    • Headaches


  • The traditional method is a good method to initiate in the ED setting where opioid overdose patients may
    present and be discharged within the same day.
  • Requires patient to be in mild to moderate withdrawal. The Clinical Opiate Withdrawal Score (COWS) may be
    used to objectively determine this.
    • Why? Need an “opioid washout period”: Allow time for the full opioid agonist the patient was taking to
      be eliminated from the body. This will prevent a precipitated withdrawal when buprenorphine is
    • D’Onofrio and colleagues studied ED initiated buprenorphine/naloxone treatment for opioid
      dependence with three study arms with a primary outcome to assess enrollment and receipt of
      addiction treatment 30 days after randomization. They ultimately found that ED initiated buprenorphine
      was more successful than brief intervention or referral alone.
  • Dosing in the ED utilizes 2-8 mg SL up to 16 mg within the first 24 hours after abstinence of opioids and the patient is
    in mild to moderate withdrawal.


  • The micro-dosing method is a good method in the ICU setting where patients may reside for several days.
  • This method allows for “overlapping induction”.
  • Additionally because of buprenorphine’s long binding time at the receptor, it should accumulate and eventually
    an increasing amount of the full opioid agonist will be replaced by buprenorphine at the opioid receptor
  • No randomized control trials to prove this method, however, several case reports have been published.


  • How supplied:
    • Buprenorphine (Subutex®) Sublingual tablet 2 mg, 8 mg
      • Will require splitting/halfing the tablets for
        micro dosing
  • Buprenorphine Belbuca® buccal: 75 mcg, 150 mcg, 300mcg, 450 mcg, 600 mcg, 750 mcg, 900 mcg
    • Buprenorphine Buprenex® injectable: 0.3 mg/mL
  • We have a unique opportunity to initiate medication-assisted treatment for opioid use disorder treatment in the
    ED or ICU settings in an effort to remove barriers to initiation
  • Buprenorphine has added pharmacologic and safety benefits compared to other therapies making it an ideal
  • The ED may utilize a traditional method to initiate therapy for their patients who may be discharged same day or
    within 24 hours
  • The ICU may utilize a micro-dosing strategy for their patients who may be concurrently receiving other opioids
    and will be in the hospital for several days


  1. Hämmig R, Kemter A, Strasser J, et al. Use of microdoses for induction of buprenorphine treatment with
    overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil. 2016;7:99-105. Published 2016
    Jul 20. doi:10.2147/SAR.S109919
  2. Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone &quot;microdosing&quot;: an alternative induction approach for the treatment of opioid use disorder in the wake of North America&#39;s increasingly potent illicit drug market.
    CMAJ. 2020;192(3):E73. doi:10.1503/cmaj.74018
  3. Naabt.org 2020. Buprenorphine Education: Technical Explanation of Buprenorpine Mu Receptor, Affinity of
    Agonist and Antagonist. [online] https://www.naabt.org/education/technical_explanation_buprenorphine.cfm
  4. Cdc.gov. 2020. Understanding The Epidemic | Drug Overdose | CDC Injury Center. [online] Available at:
    &lt;https://www.cdc.gov/drugoverdose/epidemic/index.html&gt; [Accessed 16 September 2020].
  5. Cdc.gov. 2020. Understanding The Epidemic | Drug Overdose | CDC Injury Center. [online] Available at:
    &lt;https://www.cdc.gov/drugoverdose/epidemic/index.html&gt; [Accessed 16 September 2020].
  6. Fudin, J., 2018. Opioid Agonists, Partial Agonists, Antagonists: Oh My!. [online] Pharmacy Times. Available at:
    antagonists-oh-my&gt; [Accessed 16 September 2020].
  7. D&#39;Onofrio G, O&#39;Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone
    treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-1644.
  8. Herring A. Emergency Department Medication- Assisted Treatment of Opioid Addiction. Updated August 2016. https://www.chcf.org/wp-content/uploads/2017/12/PDF-EDMATOpioidProtocols.pdf


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