Buprenorphine for Medication-Assisted Therapy in the Emergency Department

Buprenorphine +/- Naloxone
Dose
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Day 1: 2-4 mg may titrate dose, based on control of acute withdrawal symptoms every 2 hours up to a
total dose of buprenorphine 8 mg/naloxone 2 mg
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Day 2: Previous dose from day 1 if no withdrawal symptoms present; if symptoms of withdrawal
present, increase day 1 dose by 4 mg. If withdrawal symptoms not relieved after >2 hours, may
administer 4 mg; maximum daily dose on day 2: 16 mg daily.
Administration
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Sublingual film:
o
Administer film whole; do not cut, chew, or swallow. Place one film under the tongue until
the film completely dissolves, close to the base on the left or right side. If more than one
film is needed, the additional film should be placed under the tongue on the opposite
side from the first film.
Formulations
Buprenorphine+ Naloxone Sublingual/Buccal Films:
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Generic Buprenorphine HCl-Naloxone HCl Sublingual, Bunavail Buccal, and Suboxone Sublingual
Buprenorphine:
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Sublingual: Subutex and generic buprenorphine HCL
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Injection: Buprenex and generic buprenorphine HCL
PK/PD
Absorption
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Bioavailability- IM: ~95% ; SL: 31%
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Liquids reduces absoption 23% to 27%
Distribution
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Vd: 97 to 187 L (adults)
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Time to Peak Concentration- SL: 1.5-4 hours
Metabolism
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Hepatic: Extensive via CYP3A4;
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Metabolites: Norbuprenorphine: Active
Elimination
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Fecal: 69%
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Renal: 30%
Adverse Effects
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QT prolonging (less than methadone)
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precipitate withdrawal in presence of opioids/opiates
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Tachycardia, restlessness and agitation, nausea and vomiting
Drug Interactions
and warnings
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QT prolonging medications such as fluoroquinolones (moxifloxacin), macrolides, antipsychotics,
tricyclic antidepressants (TCAs)
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Strong CYP450 3A4 inhibitors: statins, amiodarone, haloperidol, macrolides, azole antifungals
(fluconazole, ketoconazole), calcium channel blockers, grapefruit juice
Pharmacy Friday
evidence-based medicine
Other pearls found at:
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www.pharmacyfriday.com
How Does Buprenorphine Works?
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Buprenorphine is a partial agonist of mu-opioid receptors as well as a weak antagonist at the kappa receptors
o
Has higher affinity to the Mu receptor ( only child syndrome and wants all of mama Mu and not too much of daddy
Kappa's attention)
o
Partial agonism ="Ceiling Effect" (All bark and no bite)
o
Slow dissociation (Doesn't know when to move on from his ex Kappmuphenia)
Induction Therapy in the ED
When to initiate?
-

Author, year
Design/ sample
size
Intervention & Comparison
Outcome
Srivastava,
2019
RCT
N=26
-
Buprenorphine
-
Clonidine
Buprenorphine group were more likely to be receiving opioid
agonist treatment at the 1-month mark compared with those
participants who received clonidine to treat their withdrawal
(P = .011)
Larochelle,
2018
Observational
N=17,568
-
Methadone maintenance
treatment (MMT)
-
Buprenorphine
-
Naltrexone
As compared to naltrexone, buprenorphine treated patient
was associated with decreases in both all-cause mortality
(adjusted HR, 0.63) and opioid-related mortality (HR, 0.62]).
D'Onofrio,
2017
Observational
N=290
-
ED-initiated buprenorphine
ED-initiated buprenorphine was associated with ↑
engagement in outpatient opioid addiction treatment
programs + ↓ illicit opioid use
Gowing,
2017
Cochrane
review
N= 3048
participants
-
Buprenorphine
-
Naltrexone
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Clonidine
-
Methadone
Buprenorphine is more effective than clonidine for managing
opioid withdrawal in terms of severity of withdrawal, duration
of withdrawal treatment, and the likelihood of treatment
completion
Berg, 2007
Observational
N=11,019
-
Buprenorphine
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Symptomatic treatment
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Placebo
Subjects who received buprenorphine were less likely to
return to the same ED within 30 days for a drug-related visit
(8%) compared to those who received symptomatic
treatment (17%) (p<0.05).

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Micromedex [Electronic].Greenwood Village, CO: Truven Health Analytics. Retrieved July 19, 2019 from http://www.micromedexsolutions.com/
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Srivastava A. Can Fam Physician. 2019 May;65(5):e214-e220.
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Gowing . Cochrane Database Syst Rev. 2017 Feb 21;2:
-
Larochelle MR. Ann Intern Med. 2018 Aug 7;169(3):137-145.
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.D'Onofrio G. J Gen Intern Med. 2017 Jun;32(6):660-666.
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Berg ML. Drug Alcohol Depend. 2007 Jan 12;86(2-3):239-44.