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.

For Buvidal® only – risk of QT-interval prolongation if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period).

  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 product^{1, 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 management^{2, 4, 5}.

For Opioid Dependence
Continue – including combination product^{1, 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 buprenorphine^{1, 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 dose^{4, 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 as^{4, 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 declining^{8, 9, 10}.

QT-Interval Prolongation (Buvidal® only) (see also Interaction(s) with other Common Medicines used in the Perioperative Period)
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 increase^{7, 10}.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include¹¹: -

• desflurane, isoflurane, sevoflurane
• thiopental (theoretical)

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).

  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 prochlorperazine^{4, 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.

QT-Interval Prolongation (Buvidal® only) (see also Interaction(s) with other Common Medicines used in the Perioperative Period)
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 increase^{7, 10}.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include¹¹: -

• desflurane, isoflurane, sevoflurane
• thiopental (theoretical)

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 withdrawal^{4, 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. Goel A, Azargive S, Weissman J et al. Perioperative Pain and Addiction Interdisciplinary Network (PAIN) clinical practice advisory for perioperative management of buprenorphine: results of a modified Delphi process. British Journal of Anaesthesia. 2019; 123(2):e333-e342
4. 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] 
5. 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]
6. 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
7. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 7^th November 2021]
8. 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]
9. 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]
10. 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]
11. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 7^th November 2021]