Buprenorphine


 

[Sublingual, Transdermal, Subcutaneous]

  Issues for Surgery


For pain relief – risk of withdrawal and loss of pain control if omitted.

For opioid dependence – risk of withdrawal, relapse and accidental overdose (if relapses) if omitted. Re-initiation would be physically painful as patient would need to withdraw from other opioids before buprenorphine could be restarted1.


  Advice in the Perioperative period


Elective Surgery

For Pain Relief (transdermal or low-dose sublingual buprenorphine)
Continue.

Transdermal patch should be left in situ; at doses up to 70microgram/hour it is unlikely to interfere with the use of full opioid agonists for acute pain management2.

For Opioid Dependence (sublingual or subcutaneous buprenorphine)
Continue – including combination product1, 3 (see Further Information for rationale).

For patient taking sublingual buprenorphine >12mg daily for opioid dependence some sources would advise tapering the dose 2 to 3 days pre-operatively following discussion with Substance Misuse team1; however, a recently published clinical practice advisory indicates buprenorphine should be continued pre-operatively irrespective of the dose3 (see Further Information).

Combination Product:

  • Suboxone® – contains buprenorphine + naloxone

See Further Information regarding the use of buprenorphine for opioid dependence.

Emergency Surgery

For Pain Relief
Continue3.

Transdermal patch should be left in situ; at doses up to 70microgram/hour buprenorphine is unlikely to interfere with the use of full opioid agonists for acute pain management2, 4, 5.


For Opioid Dependence
Continue – including combination product1, 3.

Combination Product:

  • Suboxone® – contains buprenorphine + naloxone

See Further Information regarding the use of buprenorphine for opioid dependence.

Perioperative Considerations

For Pain Relief
Absorption from a transdermal patch can be increased by heat, e.g. perioperative warming devices, whereas absorption may be reduced if the patient has poor perfusion or reduced temperature2.

For Opioid Dependence
Consider multi-modal analgesia and regional anaesthesia for pain management1. If prescribing opioids patients will need higher doses than opioid naïve patients to overcome the binding affinity of buprenorphine1, 3, 6.

Post-operative Advice

Review buprenorphine if patient develops a paralytic ileus7.

For Pain Relief
Transdermal buprenorphine patches are not suitable for acute pain or in those patients whose analgesic requirements are changing rapidly because the long time to steady state prevents rapid titration of the dose4, 7. Adjunct analgesia (e.g. Non-Steroidal Anti-inflammatory Drugs [NSAIDs], paracetamol, gabapentin / pregabalin) should be first-line for post-operative pain, where appropriate3. If inadequate analgesia persists additional immediate-release full agonist opioids (morphine or fentanyl3) should be prescribed for post-operative surgical pain (rather than increasing the strength of the patch2) but the patient’s usual buprenorphine dose should be continued. If pain is still problematic consider reducing buprenorphine dose; in which case monitor patient for 24 hours if receiving reduced buprenorphine dose while prescribed a full opioid agonist3 (see Interactions(s) with Common Anaesthetic Agents).

Where possible, patients should be discharged on their usual medication, but if strictly necessary, they may be discharged with a limited prescription of full opioid agonist in addition to their usual / a reduced dose of buprenorphine3. A clear management plan should be communicated to the GP to ensure this combination is not continued long-term (see Opioids monograph).

Transdermal patches are available as 72-hourly, 96-hourly and 7-day formulations; prescribers must ensure that the correct preparation is prescribed7.


For Opioid Dependence
If prolonged Nil by Mouth (NBM) period, or problems with enteral absorption, and buprenorphine is omitted for 3 or more days patient is at risk of overdose due to loss of tolerance; dose reduction will be needed7 - seek advice from Substance Misuse Team.

Whilst opioid analgesia is not contraindicated in substance misuse patients, alternative forms of analgesia should be considered where possible. Adjunct analgesia (e.g. Non-Steroidal Anti-inflammatory Drugs [NSAIDs], paracetamol, gabapentin / pregabalin) should be first-line for post-operative pain, where appropriate3. If inadequate analgesia persists additional immediate-release full agonist opioids (morphine or fentanyl3) should be prescribed for post-operative surgical pain but the patient’s usual dose of buprenorphine should be continued. If pain is still problematic consider reducing buprenorphine dose; in which case monitor patient for 24 hours if receiving reduced buprenorphine dose while prescribed a full opioid agonist3 (see Interaction(s) with Common Anaesthetic Agents).

Where possible, patients should be discharged on their usual medication, but if strictly necessary, they may be discharged with a limited prescription of full opioid agonist in addition to their usual / a reduced dose of buprenorphine (discuss with the patient’s Substance Misuse Team as this may impact upon their usual prescription and require additional follow up in the community)3.


  Interaction(s) with Common Anaesthetic Agents

 

Central Nervous System (CNS) Depressant Effects (also see under Interaction(s) with other Common Medicines used in the Perioperative Period)

Buprenorphine has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as4, 7, 8, 9, 10, 11: -

  • benzodiazepines
  • inhalational anaesthetics and intravenous anaesthetics
  • local anaesthetics
  • other opioids*

(Consult British National Formulary for available drugs in each class)

*Buprenorphine has mixed agonist and antagonist properties; adequate analgesia may be difficult to achieve when administering a full opioid agonist. The potential to overdose with a full agonist exists, especially when attempting to overcome buprenorphine partial agonist effects or when buprenorphine plasma levels are declining8, 9, 10.


  Interaction(s) with other Common Medicines used in the Perioperative Period

 

CNS Depressant Effects (also see under Interaction(s) with Common Anaesthetic Agents)

Buprenorphine has CNS depressant effects, which may be additive with antiemetics that also have CNS depressant effects such as cyclizine, droperidol and prochlorperazine4, 7, 11.

Macrolide Antibiotics

Clarithromycin and erythromycin are predicted to increase buprenorphine concentrations (by inhibition of CYP3A4)4, 7, 8, 9, 10, 11.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring and possibly buprenorphine dose reduction.

Risk of QT-Interval Prolongation (Buvidal® only)

Co-administration of Buvidal® subcutaneous prolonged release injections with other medicines known to prolong the QT-interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase7, 10.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include2: -

  • ciprofloxacin
  • clarithromycin
  • domperidone
  • droperidol
  • erythromycin (especially intravenous)
  • granisetron
  • haloperidol
  • loperamide (increased risk with high doses)
  • ondansetron
  • prochlorperazine

The possibility of QT-interval prolongation with concomitant administration of Buvidal® and the above listed medications is only theoretical; however, it may be prudent to monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).


  Further Information


Withdrawal

Chronic use of buprenorphine may result in physical dependence4 so abrupt discontinuation may precipitate withdrawal4, 8, 9. This may be delayed in onset, usually beginning after two days, and may last up to two weeks4. Although generally mild, symptoms include agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disorders3.

Rationale for Continuing Buprenorphine Pre-operatively

Buprenorphine is a mixed agonist and antagonist; due to concerns about achieving satisfactory analgesia post-operatively early recommendations in the literature advised stopping pre-operatively. However, this increases the risk of withdrawal, relapse and potentially overdose if patient relapses1.

Receptor binding studies show reduced but conserved availability of μ-opioid receptors in patients taking buprenorphine. Patients receiving 2mg daily have 59% of μ-opioid receptors available, this reduces to 20% at 16mg daily and 16% at 32mg. It has previously been proposed that tapering to a dose of 12mg daily will increase μ-opioid receptor availability; however, this was only recommended to start a few days prior to surgery to reduce the risk of relapse1.  Moreover, a recently published clinical practice advisory advocates continuing buprenorphine pre-operatively, regardless of dose. They suggest the buprenorphine dose should only be reduced post-operatively if pain cannot be managed by addition of adjunct analgesia and a full opioid agonist3.

Buprenorphine for Opioid Dependence

It is important to confirm with the patient’s regular pharmacy / key worker their usual dose of buprenorphine and their dosing schedule i.e. daily collection / supervised consumption.

Hospitals should have local arrangements to guide the supply of buprenorphine to patients during their inpatient stay and at discharge.


  References


  1. Lembke A, Ottestad E & Schmiesing C. Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue Buprenorphine Through the Perioperative Period. Pain Medicine. 2019; 20:425-428
  2. Simpson G & Jackson M. Perioperative management of opioid-tolerance patients. BJA Education. 2017; 17(4):124-128
  3. Summary of Product Characteristics – Reletrans® (buprenorphine) 5 microgram/hour transdermal patch. Sandoz Limited. Accessed via www.medicines.org.uk 07/09/2019 [date of revision of the text February 2019] 
  4. Summary of Product Characteristics – Temgesic® (buprenorphine) 200 microgram Sublingual tablets. Indivior UK Limited. Accessed via www.medicines.org.uk 07/09/2019 [date of revision of the text July 2015]
  5. Martin Y, Pearson A, Tranchida J et al. Implications of uninterrupted preoperative transdermal buprenorphine use on postoperative pain management. Regional Anaesthesia & Pain Medicine. 2019; 44:342-347
  6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 7th September 2019]
  7. Summary of Product Characteristics – Suboxone® (buprenorphine + naloxone) Tablets 2mg/0.5mg. Indivior UK Limited. Accessed via www.medicines.org.uk 07/09/2019 [date of revision of the text May 2018]
  8. Summary of Product Characteristics – Subutex® (buprenorphine) 0.4 mg sublingual tablets. Indivior UK Limited. Accessed via www.medicines.org.uk 07/09/2019 [date of revision of the text February 2019]
  9. Summary of Product Characteristics – Buvidal® (buprenorphine) 8/16/24/32 mg prolonged-release solution for injection. Camurus AB. Accessed via www.medicines.org.uk 07/09/2019 [date of revision of the text June 2019]
  10. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 7th September 2019]
  11. Goel A, Azargive S, Weissman J et al. Perioperative Pain and Addiction Interdisciplinary Network (PAIN): protocol of a practice advisory for the perioperative management of buprenorphine using a modified Delphi process. BMJ Open. 2019; 9:e027374