Buprenorphine

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Buprenorphine

• Dr Neil Kerfoot
• nkerfoot_at_aol.com
• Neil.kerfoot_at_gp-L81063.nhs.uk

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http//www.nta.nhs.uk/
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Which drug?
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Buprenorphine

• A synthetic opioid
• Partial agonist at the ? opiate receptor
• - Low intrinsic activity only partially activates
  opiate receptors
• High affinity for the ? receptor
• - Binds more tightly to opiate receptors than
  other opiates

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Classification of Opioids
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Mode of administration

• High 1st pass metabolism
• Bioavailability IVgt SC gt SL gt oral
• Sublingual tablets
• 0.4, 2 8 mg tablets available
• tablets take 3 to 5 minutes to dissolve
• only get half effect if swallowed

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Duration of effects

• Quick onset of action 3060 min
• Peak effects 1 4 hours
• Duration of action is dose related
• low dose (2 4 mg) 8 24 hrs
• med dose (8 16 mg) 24 hrs
• high dose (16 32 mg) 2 3 days
• (alternate day dosing a possibility?)

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Drug interactions

• Sedatives
• Mixing sedatives (e.g. EtOH, BZDs) can produce
  respiratory depression, heavy sedation, coma,
  death similar to methadone (but as BPN is a
  partial agonist, the risk of respiratory
  depression is likely to be less than that for
  methadone)
• Opioid agonists / antagonists
• BPN blocks effects of other opiate analgesics in
  a dose related way, as being a partial agonist it
  occupies so many receptors
• Hepatic enzyme inhibitors / inducers
• appears to be less impact that with methadone

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Common side-effects

• Headache
• Constipation
• Nausea
• Drowsiness, sedation
• Tiredness, lethargy
• Sleep disturbances
• Sweating
• Precipitated withdrawal on commencing BPN

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Cost of example doses per month of treatment2007
drug tariff

• Buprenorphine
• 2mg 26.88
• 4mg 53.76
• 6mg 80.64
• 8mg 80.64
• 16mg 161.28

• Methadone Mixture
• 30ml 11.32
• 50ml 21.14
• 80ml 30.24
• Methadone s/f Solution
• 30ml 12.68
• 50ml 21.14
• 80ml 33.82

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V quick look at some trial data

• Stop me if you wish a slower version!!

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RCT BPN vs Meth RetentionMattick et al 2003
Addictions
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RCT BPN vs Meth self report drug useMattick et
al 2003 Addictions
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RCT BPN vs Meth Urine resultsMattick et al 2003
Addictions
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RCT Meth vs BPN for detox Petitjean et al 2002

• N 37 (19 BPN, 18 Meth)
• Inpatient unit, Basel
• Completed detox
• 88 BPN, 89 Meth
• Conclusion
• more rapid reductions with BPN
• more withdrawal in BPN group early but less
  withdrawal when medication ceased

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So Subutex is about the same as Methadone

• BUT different!???

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• Less clouding, Which for some is good but for
  others they do not like the smaller drug effect
• Acts as a blocker at higher doses gt 8mg so can
  stop on top use

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What do NICE have to say?

• Methadone and buprenorphine (given as a tablet
  or a liquid) are recommended as treatment options
  for people who are opioid dependent.
• A decision about which is the better treatment
  should be made on an individual basis, in
  consultation with the person, taking into account
  the possible benefits and risks of each treatment
  for that particular person. If both drugs are
  likely to have the same benefits and risks,
  methadone should be given as the first choice.

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It is however a good blocker due to its high
affinity to the opiate receptor
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Occupation high with buprenorphine but not
methadone prevents effect of on-top heroin by
blocking access to the opiate receptor (Prof
David Nutt University of Bristol)
PET images
Prof D Nutt University of Bristol
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Induction into BPN treatment

• Induction from either
• dependent heroin use
• methadone treatment
• from lt 30 mg OK
• from 30-60mg difficult (suggest leave to
  specialist drug services, do not attempt in 1
  care)
• from gt 60 mg do not attempt

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Why Precipitated withdrawal

• Buprenorphine (high affinity) competes with
  displaces full agonists (heroin, methadone) from
  receptors
• Buprenorphine has lower opioid activity than full
  agonists
• Reduction in opioid activity experienced as
  withdrawal
• Only likely to occur if first dose of
  buprenorphine is given whilst client experiencing
  pharmacological effects of other opiates. Not
  likely to occur if in definite opiate withdrawal
• - Within 6 to 12 hours of recent heroin use (We
  recommend minimum 12 hour gap)
• - Within 24 - 48 hours of client on methadone (We
  recommend 24-36 hour gap in those on lt 30mg
  methadone)

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Classification of Opioids
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Features of precipitated withdrawal

• More common features include
• - sweating, anxiety, abdominal cramps, diarrhoea,
  nausea
• Commences 30 to 90 minutes after 1st BPN dose
• Peaks within 1.5 - 3 hrs after 1st dose then
  subsides gradually over 12 hours
• Minor symptoms may continue after 2nd or 3rd dose
• Symptoms may persist for days if continued heroin
  use prior to each BPN dose
• Treatment implication Symptoms will get worse if
  you give more BPN before symptoms have resolved
  this theory is being questioned now??

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Ive been in withdrawal
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Preventing precipitated withdrawal

• Time of first buprenorphine dose delay dose
  until patient in opiate withdrawal
• gt 6 - 8 hrs after last use of heroin
• gt 24 hrs after low methadone dose (lt40 mg)
• gt 48 hrs after medium methadone dose (40 - 60
  mg)
• Size of first buprenorphine dose
• less risk with low dose (e.g. ? 4 mg)
• My own practice is small dose 2-4mg and review
  same day with further dosing
• Provide information to patient carers

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Take home message is that if patient in
withdrawal then induction or change from
methadone will go well

• If not in withdrawal at first dose may fail so
  ask patient how long until they experience
  withdrawal from their drug. If they do not know
  advise trying on Sunday take home dose

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Low dose methadone transfers (lt40 mg)
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Reviewing patients during induction

• Good induction regular frequent review
• Patients often need reassurance, particularly if
  precipitated withdrawal or early side-effects
• Review every 1 - 2 days if possible (I review
  daily for 3 days)
• Should review patient before 3rd dose
• Dose increases only after review with clinician
• Do not authorise automatic dose increases
  (BSDS)
• Increases in bup dose can occur daily Dose
  increases usually by 2 to 4 mg at a time but
  could go 8mg 1st day and 16mg 2nd day if patient
  has a big opiate habit this faster induction can
  be beneficial as methadone induction happens over
  a few weeks

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Urine testing

• Not routinely tested for by NBT lab
• Can contact them and ask for individual patient
  test
• Once part of PBC and tariff may be cheaper to
  purchase immediate result testing kits
• Therefore urine will be negative to all and so
  watch for potential switches to child's urine etc

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Detox?

• How realistic is the request?
• 57 of patients first accessing treatment
  services request detox
• Only 5 of heroin dependant patients each year
  achieve durable abstinence

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Withdrawal

• Slow reduction 12-10-8-6-4-3-2-1.6-1.2-0.8-0.4
  over an agreed timescale
• More speedy reduction 8,6,4,2 then stop over 4-8
  days with lofexidine, sleeping tablets and PRN
  meds (ACER UNIT)
• If the drug user is mentally prepared for
  withdrawal it is more likely to work.
• Prior to this ask shared care worker to arrange
  and agree an after care plan
• Remember - Detox is good for many things but
  abstinence is not one of them

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Which drug 2007 draft guidelines
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Symptomatic Relief 2007 draft guidelines
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Draft clinical guidelines 2007
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Community Detox in South Glos

• Issues and potential concerns that need to be
  addressed

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The futureSuboxone?

• Buprenorphine and naloxone
• Partial agonist and full antagonist
• Bioavailability? Prevents IV diversion
• Cost?

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Phew that was a bit of a rollercoaster
Questions?