Opioid Use Disorder Flashcards
overview of continuum of care
withdrawal management is considered the lowest treatment intensity option.. Then we shift over as treatment intensity increases to what are the more conventional agonist therapies. And these are the oral options which includes buprenorphine, naloxone,AKA suboxone. As well as methadone. And then as we continue to shift towards higher treatment intensity, we have a further oral option, which is an expert
led treatment option, and this is slow-release oral morphine, the brand name Kadian
And then finally, the most high-intensity treatment options which are diacetylmorphine, and injectable hydromorphone
harm reduction spans the entire length of treatment intensity.
withdrawal correlates to a loss of tolerance, which puts people at an increased risk of death if they returned to their original substance use patterns. So very quickly when we are in a state of abstinence from a substance, we lose tolerance very quickly. And again, if we return to either the same amount that we were consuming or perhaps a different batch which is more potent or at a very high risk of death because we have a loss of tolerance, withdrawal management is considered a low treatment, intensive treatment intensity option, but it’s very high-risk for patients
focus on opioid agonist treatment. Because again, this is the gold standard of care for the treatment of opioid use disorder
the goal is to achieve a stable dose where a patient does not experience any symptoms of withdrawal for approximately a 24 hour period while also balancing Not like not having any symptoms of over medication
Buprenorphine/naloxone (Suboxone®
● Partial mu opioid receptor agonist with high binding affinity; antagonist at kappa
receptor
○ Strong binding affinity
■ Good at blocking effects of other opioids
● Important to consider this when managing acute pain
■ Slow dissociation - long relief of withdrawal symptoms
● Can miss up to 5 consecutive days before re-initiating required
■ Better safety profile
● Decreased risk of overdose - ceiling effect for respiratory depression
○ More flexibility for carries
■ Standard doses are well below lethal threshold for someone whose opioid naive
■ Well tolerated - limited side effects and euphoria
■ Risk - precipitated withdrawal
if someone is using a full agonist opioids, it binds to their receptors and let’s say it turns the receptor volume up to 100%. So the patient is experiencing all those pleasurable effects that we talked about, those reinforcing effects. Then if we introduce a partial agonists that has a very high binding affinity, it comes into the system, bumps off the full agonist and it attaches to that receptor. But instead of turning the volume onto 100%, maybe it only turns the volume on to 65% or 70%. So we still have the opportunity to have a lot of those benefits, but we have a lower risk of some of the negative side effects
So one characteristic that’s unique to buprenorphine naloxone compared to other OAT options, is people can actually miss several days in a row and still experienced relief from their withdrawal symptoms and not have that same dramatic loss of tolerance according to guidelines, patients can actually miss up to five consecutive days of their buprenorphine naloxone dose before treatment has to be completely restarted
precipitated withdrawal
state of acute and severe withdrawal that occurs if the inital dose of buprenorphine is given when pt has other opoids active on the receptors
if buprenorphine naloxone is started too soon within the time that they last used a full agonist, they will experience precipitated withdrawal and patients will never, ever want to try buprenorphine naloxone again because it’s basically zero to 100 on your withdrawal symptoms.
this is a state of acute and severe withdrawal that’s brought on by buprenorphine, naloxone being started too early, bumping off full agonists when they’re still a high amount of full agonists in the system and then causing this net opioid deficit which causes intense withdrawal symptoms.
if we have someone who’s receptors are activated at 100%. And then we introduce, introduce buprenorphine naloxone, that full agonists gets bumped off and the receptor quickly goes from 100% to 70%. People are going to feel really poorly.
Buprenorphine/naloxone (Suboxone®
● A preferred treatment option
○ Newer data states equivalent to methadone in retaining patients to care - important to get to
the right dose, in a timely way, and to be flexible
● Formulation:
○ Sublingual combination tablet (4:1 buprenorphine:naloxone ratio)
■ 2mg/0.5mg tablets, 8mg/2mg tablets
■ (Other combination tablets not covered by ABC; covered by NIHB)
○ Sublingual dosing
● Classic induction vs. micro induction
● Maximum dose range: 24mg/day (or 32 mg/day)
● Can present challenges for acute pain management
So naloxone actually isn’t absorbed sublingually. So when patients take their buprenorphine naloxone tabs, dissolve it under the tongue, then a lock zone actually is essentially inert like it’s not working because it isn’t absorbed sublingually. What it’s intended to do is to prevent people from injecting buprenorphine naloxone because if they crush up the buprenorphine, buprenorphine, naloxone and tablets and then administered by IV or subq, IM
Sublingual dosing important If this dose is taken orally, it will not work, so it must be absorbed so sublingually. And obviously this can pose some challenges. Patients find that it can take a long time to dissolve
You can encourage patients to drink water before their sublingual dosing. So when we increase the moisture in the mouth, then we have a faster rate of dissolution. The monograph actually says to not break up tablets, but in practice this is actually done quite commonly. So if you break up the tablets, obviously more surface area, faster dissolution rate.
No longer on triplicate
Can be used in pregnancy, keep them stable on their dose so no neonatal distress
COWS and SOWS
COWS on left
- providers will objectively rate the symptoms of withdrawal based on patient report and their objective presentation. Again, moderate is considered a score of 12 or greater.
SOWS on right
patient administered tool. And so they would have self-rate their own symptoms. And this is typically done in the context of a home on left
- providers will objectively rate the symptoms of withdrawal based on patient report and their objective presentation. Again, moderate is considered a score of 12 or greater.
SOWS on right
patient administered tool. And so they would have self-rate their own symptoms. And this is typically done in the context of a home
Buprenorphine - novel formulations
● Probuphine®
- buprenorphine subdermal implant
○ For the management of opioid dependence in patients clinically stabilized on no more than 8 mg of
sublingual (SL) buprenorphine for the preceding 90 days
○ Must be implanted by trained provider
○ Special authorization under ABC, limited use benefit under NIHB
It does need to be implanted by a trained provider.
implanted into the bicep area
● Sublocade®
- buprenorphine extended release injection
○ Per monograph, can be initiated for patients who have been stabilized on an equivalent of 8-24mg SL
per day for a minimum of 7 days
■ Clinical practice is already exploring novel ways of rapidly initiating buprenorphine extended
release injection
○ Typical dosing regimen: 300mg SC q1month x 2 months then 100mg SC q1month
○ Open benefit through ABC (including OAT gap coverage program), limited use benefit under NIHB (no prior approval required)
the product is very viscous and it comes with a very specific needle tip that has to be used. And it’s very long. I think it’s 19 gauge for patients overall. It can be a little bit concerning, can be quite painful the first time
do not administer this by any other route than sub-Q
Encourage patients to ice the area before for at least 15 min to try and reduce pain
It isn’t unusual for patients to actually have a visible depot in that area after the injection is administered
Methadone
Full agonist (mu opioid receptor)
○ Slow onset of action - peaks at 2-4 hours
○ Long elimination half life (24-36 hours)
■ Doses must be titrated slowly to avoid the risk of accumulation; slow to achieve
therapeutic dose
○ More potential for interactions
■ Primarily through CYP450 3A4
● Inducers - lower serum MMT levels (ex: CBZ, PHT, chronic EtOH)
● Inhibitors - raise serum MMT levels (ex: ciprofloxacin, acute EtOH, SSRI, macrolides)
■ With other agents that cause respiratory depression
■ With other agents that prolong QTc
○ High risk for overdose
○ More serious side effect profile
■ CNS depression, constipation, sweating, hypogonadism, weight gain, dental concerns
○ Loss of tolerance occurs quickly - importance of last dose verification
we may not see that sedation acutely in the pharmacy post dose, but they may be experiencing it later on in the day.
doses must be titrated slowly to avoid the risk that it accumulates in our body. So typically what we see is that the dose will increase every 3 to 5 days
providers might be more inclined to start at a higher starting doses because it takes so long to get to a stable dose of methadone. As long as they can deduce that the patient will be able to tolerate that. Then 30 mg is typically the starting dose that I saw the most often.
- And those increases every three days. It’s typically by 10 mg at the most
Methadone does not actually have a maximum dose. So this is titrated based on patient-specific tolerance
Lots of tolerance can occur in as little as three days. So it’s very important if patients are missing doses, those doses often have to be adjusted. T
Methadone
● A preferred treatment option
formulations
○ Large body of evidence - has the most evidence for use in pregnancy
○ Studies show efficacy for decreasing drug use, improved treatment retention, decreased
transmission of HIV and Hepatitis C, decreased overdose and premature mortality, as well as
decreased criminal behaviour
● Formulations:
○ Unflavored oral liquid 10mg/mL - dispensed in crystalline juice (qs to 100mL) to minimize risk of
diversion and improve taste
○ Tablets - typically not used for OAT, typically for chronic pain
● Starting dose depends on level of tolerance and risk (5mg-30mg)
○ Typically increase by 10mg q3 days
○ Frequent reassessment required - balance management of withdrawal and cravings with
oversedation and other adverse effects
● No maximum dose
● MMT provides some blocking effects for other opioids
○ Not effective for acute pain in dependent patients - will need short acting agent in addition to MMT
Methadone - missed doses
missed days
1-2 smae dose
3-4 days
30mg same dose
31-60 restart at 30mg
>60mg restart at 50% of prev dose
5 or more restart at 5-30mg (depending on tolerance0
here’s different guidance on how doses should be pursued. Again, prescribers may handle this very differently. And the CPS has suggested that physicians can use any regimen that they want as long as it’s within a guideline.
ECG
● Specific to methadone maintenance monitoring
● Typically completed:
○ Prior to initiation
○ Within 30 days of initiation
○ If the dose meets or exceeds 100mg and thereafter at every dose that meets or exceeds
multiples of 20mg
○ If the patient experiences unexplained syncope, seizures, or other symptoms suggesting
cardiac involvement
○ If the patient is initiated on a medication that prolongs QTc
once patients have, are reaching an ECG of 450 and up, that’s when we’re becoming really more concerned. We’re monitoring more frequently. And as that goes, creeps up higher. If it gets closer to, I would say like anywhere above 480, that’s where more maybe starting to consider if we can if we should be considering another agent
Urine drug screening
● Often integrated into treatment plan with opioid agonist treatment
● Purpose:
○ Confirm reports of substance use
○ Identify presence of concerning substances
○ Monitor for treatment efficacy
○ Monitor for treatment adherence
● In Alberta, automatically screens samples for all substances (including some
metabolites)
● Not intended to be punitive
● Frequency of UDS may depend on patient specific factors
Specialist-led treatment options
Slow release oral morphine (SROM)
● Consider for those who have not stabilized on or have contraindications to
preferred treatment options
■ Data suggests better than MMT for overall patient satisfaction, reducing cravings,
reducing symptoms of persistent mild depression
● Kadian® (24 hour morphine product) is the only formulation studied
○ Full range of doses studied: 60-1200 mg/day
○ Typically once daily as OAT
○ Requires diligent measures to avoid diversion and mitigate risk of overdose
■ Capsules are opened into a med cup, ingestion of beads witnessed (sometimes mixed
with applesauce)
■ Cannot crush or chew pellets
This is typically pursued for patients who’ve maybe try buprenorphine and methadone, not been able to achieve therapeutic effect or have contraindications to those therapies.
This is typically dosed once daily. It’s always witness ingestion.
It’s really important that they do not crush or chew the pellets in their mouth because then that disrupts the effect
released over 24 hour period. But patients can lose tolerance very quickly. So despite this delayed absorption, it does still have a short half-life, which is what causes this loss of tolerance.
SROM - missed dose management
see slide 16
Specialist-led treatment options
Injectable opioid agonist treatment (iOAT)
● Specialist-led, high intensity treatment option
● Goal - harm reduction
○ Reduce harms related to IVDU including reducing infections and transmission of BBV (HIV,
HCV)
○ Reduce the use of illicit opioids
○ Engage patients into care - create connections
● Patients self administer prefilled syringes of HYDROmorphone IV/IM up to
three times a day in a supervised setting
there was non-inferiority studies that were done between diacetylmorphine and injectable hydromorphone. And what they found was that generally patients derive the same benefit from IV hydromorphone, but there was a lot less barriers to acquiring the product.
Acute pain management in the context of OUD
● Undertreated acute pain is a risk factor for returning to or ongoing use
● Do include non-opioid pharmacotherapy as appropriate
● Opioids can be used safely in patients with a history of opioid use disorder but
should be carefully monitoring
● Complaints of pain should be taken seriously
OAT replaces opioid debt. It does not also manage acute pain
