- Sublingual tablets either as buprenorphine alone (Subutex) or pre-mixed with naloxone (Suboxone)
- Onset 30-60mins, peak effect 1-4hrs and duration 6-12hrs i.e. suitable for acute pain
- Typical starting dose for acute pain 200-400μg SL
- Transdermal patches delivering 35µg/hr, 52.5µg/hr, or 70µg/hr (maximum daily dose is two 70µg/hr patches which is 3.36mg)
- Takes 24hrs to provide clinical effect and 72hrs to reach peak effect therefore not suitable for acute pain
- A preparation for IV/IM use is available
Buprenorphine
Buprenorphine
- A semi-synthetic opioid with structural similarity to morphine which is used primarily as substitution theray in patients with opioid dependence
- High lipid solubility makes it suitable for transdermal use
- Partial MOP receptor agonist; higher affinity than morphine
- Partial NOP receptor agonist
- Unclear effect on DOP and KOP receptors; low degrees of partial agonism, inverse agonism and antagonism all reported
- Dissociates slowly from receptors therefore has a long duration of action
- Oral bioavailability only 10%; sublingual bioavailability is 33%
- Metabolised by CYP3A4 (Phase I), followed by conjugation (Phase II)
- Duration of action approximately 10hrs
- Excreted by biliary (70%) and urinary (30%) routes
- Most of the adverse effects from MOP agonism, rather than an NOP effect
Respiratory
- Ceiling effect on respiratory depression i.e. at a certain point more buprenorphine causes better analgesia without increased risk of OIVI
- However, if OIVI does occur it's very difficult to treat owing to high MOP receptor affinity, with higher doses and longer infusions of naloxone required
Neurological
- Causes analgesia when given at low doses; analgesic potency approximately 60x that of morphine
- At higher doses, its NOP receptor effect predominates and it can therefore cause antanalgesia
Gastrointestinal
- Sublingual administration makes it suitable for those who are NBM
- Less constipation than other opioids
- Risk of prolonged, severe nausea and vomiting
Renal
- Does not rely on renal pathways for elimination so suitable in those with renal failure
- Fully removed by (haemo)dialysis
- PAIN Network (2019) recommendations include:
- Almost always appropriate to continue buprenorphine, rarely appropriate to reduce dose
- Consider dose reduction if inadequate analgesia despite reasonable doses of full opioid agonist; close monitoring is required
- Use a multi-modal analgesic regimen including regional anaesthesia
- Typically prescribed as a sublingual tablet with maintenance doses between 12-24mg
- Daily doses of >12mg block all opioid receptors with high affinity, making acute pain management difficult
- Theoretical risk of opioid withdrawal if inadequate levels of full opioid agonists are used for acute pain relief instead of buprenorphine
- Conversely, risk of opioid withdrawal if buprenorphine started in patients receiving long-term full agonists
- Continue usual buprenorphine dose and provide additional full opioid agonists for acute pain management, alongisde multi-modal analgesia and pain team input