buprenorphine

benefits of buprenorphine vs methadone

benefits of buprenorphine vs methadone

lower risk of OD

fewer drug int (esp QT meds)

lower cardiac risk

lower risk of interaction/OD with alcohol and benzos

shorter time to stabilization

does not always require daily observed dosing at pharmacy

MOA of buprenorphine

dual activity at opioid receptors

partial agonist at mu receptors

high affinity- binds strongly, not displaced by other opioids except fentanyl therefore makes other opioids less rewarding/reinforcing.

slow dissociation prevents w/d for 24hr

low intrinsic activity- provides enough opioid agonist activity to prevent w/d and cravings with less euphoria and sedation than full agonists

kappa receptor antagonists

benefit of ceiling effect

ceiling effect w/ resp depression and OD- leads to enhanced safety

what happens when combine benzos/alcohol w/ buprenorphine

lose safety advantages (still less risky than combining these drugs w/ MTD)

con of ceiling effect

makes it less effective for heavy users, may need to use methadone

max dose of buprenorphine

24-32mg (no additional effects)

naloxone moa in Suboxone

high affinity mu opioid receptor

full antagonist

high IV F, very poor oral F

no clinical effect via s/l route

added to limit IV abuse

half life of buprenorphine

38hrs (25-70hrs) after s/l admin

what do urine toxicology tests measure

norbuprenorphine levels

two main approaches to buprenorphine dosing

traditional induction

micro-induction (macrodosing, or Bernese method)

what is the traditional induction method for buprenorphine

goal of induction is to titrate as quickly and as safely as possible

can get to an efficacious dose rapidly + rapid control of sx

what is precipitated w/d

development or worsening of w/d if buprenorphine is started too early

if started when receptors are fully loaded with an opioid- buprenorphine will readily bump the opioid off due to it’s high receptor affinity

as a partial agonist it only partially stimulates the receptor leading to less intrinsic opioid activity

how to prevent precipitated w/d

start when mod w/d sx are present:

receptors no longer fully occupied- the abused opioid has begun to come off the receptors naturally

when COWs score is 13+

if using short acting IR opioid/heroin how long to wait to start buprenorphine

at least 12hrs

if using intermediate acting (CR/SR/LA) opioids how long to wait to start buprenorphine

18hrs

if using long acting opioids (methadone, fentanyl patches) how long to wait to stop buprenorphine

at least 72hr

if someone is using street fentanyl how long to wait to start buprenorphine

24-48hrs (unsure)

buprenorphine induction dosing on day 1

2-4mg (sometimes 6) of Suboxone as initial supervised dose when pt is in mod-severe w/d (COWS 13+)

reassess pt after 1-3hrs and Rx additional observed doses if necessary (COWS 9+, sx of w/d) of 1-2 2mg tabs

max dose on day 1 buprenorphine

12mg

if pt is at high risk of precipitated w/d (ex: LA opioids) or if they have been abstinent what is starting Suboxone dose

2mg

how long does relief of w/d start after 1st Suboxone dose

20-40min

how long after Suboxone dose may precipitated w/d occur after first dose

30min

if someone is in severe w/d (COWS 24+) what does of buprenorphine may you start with

6mg

how to dose day 2 buprenorphine

if no w/d sx give total dose from day 1

if w/d sx present (COWS or sx) add 4mg to day 1 dose

if w/d sx still present after 2-3hrs, give another 4mg

when is optimal dose usually reached on Suboxone

day 3

list all instances when you may increase buprenorphine dose

w/d sx present but improving

cravings still present

ongoing use of opioids

no sedation at current dose

which patient populations may you use a slower titration with

older adults, pts taking other CNS depressants, pts with questionable opioid tolerance

how would you titrate patients that you decide need a slower titration (ex: elder)

increase by 2-6mg per day until optimal dose reached

How do you know you’ve reached an optimal dose

24hrs of no w/d sx

no cravings to use opioids

no toxicity

2 options for precipitated w/d

abort induction and try again later (sx treatment and set new date)

continue induction (preferred method)

how would you continue an induction in someone in precipitated withdrawal

give additional doses of 2mg q 1-2hr until resolved

may worsen withdrawal before improvement

day 1: do not exceed 12mg daily, offer sx Tx

agents to treat anxiety from w/d

clonidine, quetiapine

agents to treat sleep problems from w/d

trazodone

agents to treat pain from w/d

ibuprofen

agents to treat nausea from w/d

ondansetron, dimenhydrinate

agents to treat diarrhea from w/d

loperamide

alternative dosing strategy that is similar to induction

add up dose on day 1, admin as first dose on day 2, followed by additional doses based on re emergence of w/d sx

on day 3, add up the doses admin on day 2 and provide extra as needed

repeat daily until pt is stable (no w/d, COWS <8 for 24hrs) or until max 24mg achieved

what is the Bernese method

uses small titrating doses of buprenorphine

causes gradual accumulation and occupation of buprenorphine at opioid receptors bc of high mu affinity and slow dissociation

benefit of Bernese method vs normal induction

does not require person to be in moderate w/d therefore pts prefer

microdosing dose titration

0.5mg bid, increasing doses to a total daily dosage of 12mg over 5-7 days

rapid microdosing titration

0.5-1mg at shorter intervals, up to 12mg total in 24hr period

indications for microdosing

ppl who are on methadone or use fentanyl (long t1/2)

ppl who cannot tolerate w/d

ppl who should not undergo w/d for medical reasons (pregnancy, CAD)

continuoud opioid users

how many missed days of suboxone until you have to change the dose

6 days

or 2 alternate daily doses (ex: if on MWF)

what to do if someone is on suboxone and completely relapse

advise them to stop using suboxone until they are ready to return

what is macrodosing

using a high dose of buprenorphone to try to displace all other opioids and push beyond precipitated withdrawal causing effective symptom management due to buprenorphines high affinity and long acting activity

often done in ED setting/inpatient/ambulatory clinic

macrodosing dosing

8-16mg at a time, repeat 8mg q hr if ongoing w/d + no sedation to a max of 24-32mg

when to consider buprenorphine implant

consider for convenience in clinically stable pts

consider implant if stable on 8mg or less

requires abstinence of opioids

when to consider buprenorphine injection

mod-severe OUD who have been stable on suboxone 8-24mg for atleast 7 days

dosing of buprenorphine injection

300mg monthly x 2 doses then 100mg q 28/7

can be given 2 days early, 2 weeks late without dose adjusting

who is alternate day dosing an option for

stabilized pts at doses 12mg or less per day (ex: 24mg q 2 days)

**do not just use so pt can have fewer pharmacy trips, consider take home doses or extended release formulations

how to do alternate day dosing (q 2/7)

decrease frequency to every other day but double the daily dose

8mg daily to 16mg q 2/7 (max 24mg/day)

How to do MWF dosing

Monday and Wednesday- twice the dose
Friday- 3x the dose

max is still 24mg daily

what is max original daily dose if thinking of doing MWF dosing

8mg

Who is eligible for carries

pt is clinically stable and can store med safely at home (Secure, lock cabinet etc)

are patient outcomes better with daily witnessed dosing or carries

quicker transition to take home dosing can improve tx retention and adherence

what are some reasons to restrict pts to daily witnessed ingestion

increased engagement can potentially promote pt safety and Tx adherence

homelessness, other reasons for inability to safely store meds

evidence of pt diversion of meds

ongoing substance use, esp benzos/alvohol

length and track record of clinic attendance

severe behavior issues, cognitive impairment, unstable mental health

can buprenorphine be abused

less desirable to abuse bc of low intrinsic activity (partial agonist)

if injected get w/d sx due to naloxone componenet, also bc buprenorphine is partial agonist and displaces full agonist opioids if abusing

can you OD on buprenorphine

if inject high dose, naloxone has shorter t1/2 so it wears off and then the buprenorphine takes over and you can OD

also taking benzos/alcohol increases fatality risk

AE of buprenorphine

H/A, insomnoa, anxiety, nausea, ab pain, constipation, sweating

rare reports of LFT elevation

pharmacodynamic buprenorphine interactions

CNS depressants (alcohol, benzos, Z drugs, antipsychotics, antidepressants)

Precipitated withdrawal

OTCs- dimenhydrinate/diphenhydramine (abuse potential, sedative/anticholinergic properties)

anticholinergics (severe constipation, paralytic ileus)