BUPRENORPHINE

MANAGEMENT
Dr Brenda Mogaka
Ngara MAT Pharmacy Lead
Objectives
At the end of the training the participants will :
• Have a better understanding of how Buprenorphine works
• Be able to choose between MTD and BHD according to patients’
needs
• Be able to feel confident during initiation, follow up and specific
management of patients under BHD For MAT clinic healthcare
workers
Outline of Presentation
• Buprenorphine pharmacology
• Eligibility criteria
• Induction, maintenance and cessation of Buprenorphine
• Methadone vs Buprenorphine
• Side effects and contraindications
• Role of psychosocial interventions in Buprenorphine management
• M&E
• Way forward for Ngara MAT
Buprenorphine MoA
Buprenorphine is an effective treatment for opioid use disorder.
 As a high-affinity, partial agonist for the mu-opioid receptor
• Binds strongly and is long-acting
• Displaces and block full opioids : precipitate withdrawal
It dissociates slowly from the receptors resulting in prolonged therapeutic
effects and therefore many patients may not have to take it daily.
This “ceiling effect” lowers the risk of misuse, dependency, and side effects.
Buprenorphine suppresses opioid withdrawal and craving, reduces illicit opioid
use, and blocks exogenous opioid effects including respiratory depression.
Pharmacokinetics
• Absorption:
Poor oral bioavailability because of   extensive first-pass metabolism and inactivated by gastric acid.
 Sublingually is extensive enough to make this a feasible route of administration for opioid use disorder 
• Administration:
sublingual tablet ( 2mg and 8 mg)
transmucosal tablets and films
6-month implantable and
monthly injectable products
• Metabolism:
It is extensively metabolized by N-dealkylation to norbuprenorphine by cytochrome P450 (CYP) 3A4.
 Onset : 30-60 minutes
 Peak : 1-4 hours
 Half life : 20-73 hours
• Elimination: . The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values
ranging from 3 to 44 hours). majorly eliminated in the faeces, with approximately 10-30% excreted in urine. 
• Distribution: A large volume of distribution and is highly protein bound (96%).

• Naloxone has been added to a sublingual formulation of buprenorphine (1:4)to reduce the abuse liability of the product.(Suboxone)
• Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk.
Eligibility Criteria
• BHD is NOT to replace MTD but to widen the possibilities.
Patient with CI for MTD (cardiotoxicity)
 Patients with less than 1 year use of heroin
Patients with need of alternate dose
 Patients with need of short treatment
 In the process of cessation (as starter or after MTD)
 Clients taking Methadone doses less than 40mg
 Clients who have been on regular MAT treatment and have chosen the
treatment
Inductions, Maintenance and Cessation
 Induction from heroin (short acting)
• Last dose of short acting opioids > 12h
• Mild withdrawal (COWS 8-10) ***
 Induction from MTD (long acting)
• Decrease dose of MTD to 40mg
• Last dose of long acting opioids > 36h
• Mild withdrawal (COWS 8-10) ***
• No further MTD dose administrated once BHD started
Maintenance
• Repeat the process of adjusting the dose to symptoms until
withdrawal disappear
• Maintenance = when reaching stable daily dose
• Daily dose between 16mg and 24mg, rarely 8mg or 32mg
• If need to increase above 16mg :
 • Check for interactions explaining not a full effect
• Observe if SL properly taken and repeat instruction
 • National Guidelines *** : 5 days at 16mg before increasing
• Withdrawal symptoms at 32mg = max dose (ceiling effect) • Ceiling effect
can explain withdrawal symptoms . Consider switching to methadone
Follow-up
• How have you been doing since I last saw you?
• Symptoms of withdrawal (COWS ***) / intoxication
• Type of symptoms?
• How long after the last dose?
• Other substances used : increasing / loss of control?
• Sign of low dose
• Mixing with heroin?
• Sign of low dose
• Look actively for side effects
Alternate dosing
• BHD allows alternate dose : high affinity & slow dissociation
• How to ?
• Patient must be stabilized
• Decide with the patient on the type of alternate dose
• Every other day or Every third day or 3/week
• Increase dose on dosing day by the among not received on other day
• E.g. if on 8mg daily switch to 16/0/16/0mg
• E.g. if on 8mg daily  switch to 16/16/24mg on Mon/Wed/F
Cessation
• • Design a tapering plan based on patients’ needs

> 28 days tapering plan : better outcomes than shorter plans

• Decrease by 25% per 5-10 days is said easily tolerable
• Withdrawal symptoms = tapering too quick = risk of relapse
• E.g. initial dose of 16 mg /day
• Day 1: reduction of 25% to 12 mg/day
• Day 6: reduce dose from 12 mg/day to 8 mg/day
• Day 11: 4 mg/day
• Day 16: 2 mg/day
• Day 24: 1.50mg/day
• Day 31: 1mg/day
• Day 39: 0.75mg/day
• Day 45: 0.50mg/day
COLD TURKEY?
Cessation
• • What we know
• • Best outcomes if following 1 to 2 year with no drug use
• • Worse outcomes if trt shorter than 6 months
• • No evidence to support stopping MAT
• • 95% of methadone patients do not achieve abstinence when attempting
to taper off (Nosyk, et al. 2013)
• • Over 90% of buprenorphine patients relapse within 8 weeks of taper
completion (Weiss, et al. 2011) • National guidelines criteria’s *** • On MAT
for >12 months
• • Score of 10 from a list of questions
 Methadone vs METHADONE
Buprenorphine BUPRENORPHINE
MoA Full agonist Partial agonist
Dose Daily Daily/Alternate
Half life 24-36hrs 20-73hrs
Metabolism CYP 3A4, 1A2, 2D6 CYP 3A4
induction Patient not to be in withdrawal Patient to be in withdrawal

Risk to naïve person Increased Reduced(wide safety margin)

Abuse potential and overdose High Low
Taper off Slow taper over weeks and months Easy to withdraw
Information Well known among PWUD Not well known
cost cheap expensive
Indication All levels of opiod dependancy Mild-moderate opiod dependancy
• Despite the obvious benefits conferred by the ceiling effect,
buprenorphine prescriptions have failed to overtake methadone in the UK
• Low Retention in treatment with buprenorphine
• Where comparison is possible, flexible dose methadone maintenance
( US$23,100) performs somewhat better in terms of quality-adjusted life
years than buprenorphine (US$44,550) when both are compared to no
drug therapy for heroin users.
•  Due to its weaker efficacy, buprenorphine is probably best restricted
those with mild–moderate dependence, whereas methadone can be used
with all levels of dependence.
•  Precipitated withdrawal. Inducting heroin users requires caution and
transferring patients from methadone runs a particular risk of an extended
precipitated withdrawal syndrome because of methadone's long half-life
Side effects and contraindications

The most commonly reported adverse events with SUBOXONE include:

headache (36%, placebo 22%),
withdrawal syndrome (25%, placebo 37%),
nausea (15%, placebo 11%),
insomnia (14%, placebo 16%),
sweating (14%, placebo 10%).
Contraindications

• Contraindicated drugs
• Significant psychiatric co-morbidity
• Multiple previous opioid addiction treatment episodes with frequent relapse during those episodes (may also
indicate a perfect candidate)*
• Nonresponse or poor response to buprenorphine treatment in the past
• Impaired hepatic function
Drug interactions
BENZODIAZEPINES Deaths have been known to occur as a result of the
combination of buprenorphine with benzodiazepines for
example diazepham, valium etc.(especially injectable).

ALCOHOL May impair metabolism of buprenorphine.Combination may

also lead to death(Respiratory distress)
ANTI-DEPRESSANTS Some anti-depressants including tricyclic antidepressants
and monoamine oxidase inhibitors (MAOIs) should be
prescribed with caution due to possible sedation.
OTHER FULL AGONISTS Buprenorphine may precipitate opioid withdrawal syndrome
when given to those taking full opioids agonists.
Buprenorphine reduces the effects of other opioids given for
analgesia
ART No significant interaction with HIV combination therapies

ANTI-tb Rifampin may cause reduced buprenorphine levels, causing

withdrawal symptoms.
Increase dose of BUP
Dosing
• Sublingual tablet (film/tablet) Due to extensive first-pass liver metabolism, oral dosing
of buprenorphine results in low bioavailability and is not feasible
• 2mg or 8mg
• Avoid acidic drinks before administration but moisten mouth with water.
• SL tabs hold under the tongue for several minutes until complete dissolution
1 tablet, place it under your tongue, lean your head slightly forward, and let the tablet dissolve
completely.
2 tablets, place both of them under your tongue, 1 on the left side and 1 on the right side
If you have more than 2 tablets to take, put the next tablet(s) under your tongue after the first
tablets have dissolved completely

• Nodrink, no talk, no swallow until complete dissolution

Takes 5-10 minutes to dissolve completely
Role of Psychosocial Intervention
• Psychoeducation
• Support and reassurance in managing the first 5 days of treatment
Monitoring & Evaluation
• Pharmacovigilance
• Reporting tools
• P4 client dispensing chart
• P7 monthly consumption report and request form
• P8 monthly MAT patients’ summary report
Wayforward for Ngara
• Evaluate for eligible clients
• Ordering Buprenorphine from KEMSA
• Identify the relevant reporting tools
• Pharmacovigilance
• Client education and support
• Increase knowledge through CME
REFERENCES

• National Guidelines for MAT

• Karuri MAT presentation
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271614/#
• https://www.stevenvgupta.com/PatientBrochure.pdf
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154701/#