Buprenorphine for the Management of Chronic Pain National Guidance Document March 2024

Buprenorphine for Management of Chronic Pain

Buprenorphine for the Management of Chronic Pain

National Guidance Document

March 2024

VA Pharmacy Benefits Management Services and the National Formulary Committee in Collaboration with

the VHA National Office of Pain Management, Opioid Safety and PDMP (PMOP)

The following recommendations are based on medical evidence, clinician input, and expert opinion. The content of the

document is dynamic and will be revised as new information becomes available. Local adjudication should be used until

updated guidance and/or CFU are developed by the National PBM. The purpose of this document is to assist practitioners in

clinical decision-making, to standardize and improve the quality of patient care, and to promote cost-effective drug

prescribing. The drug Product Information should be consulted for detailed prescribing information.

1. Background

Pain Management, Opioid Saf ety, and Prescription Drug Monitoring Program (PMOP) and PBM

Formulary service are providing guidance on use of buprenorphine for outpatient pain management. This

field-based guidance was created to provide clarity on the use of buprenorphine f or outpatient pain

management with input from the PMOP Buprenorphine Subject Matter Expert (SME) Workgroup. It is

recommended that the principles of LTOT prescribing for full mu agonist opioid medications are applied to

prescribing buprenorphine f or pain, particularly in the absence of Opioid Use Disorder (OUD).

2. Care Considerations in Use of Buprenorphine for Chronic Pain

a. LTOT principles outlined in VA/DoD Clinical Practice Guideline f or the Use of Opioids in the

Management of Chronic Pain (VADoDOpioidsCPG.pdf) s

hould be followed when prescribing

buprenorphine f or pain, including:

LTOP should primarily focus on functional improvement in physical, social, and psychological

domains consistent with the biopsychosocial model of care.

o Opioid analgesic medications have less evidence of benef it and higher risk of potentially

serious adverse outcomes with LTOT compared ot short term prescribing f or pain.

o Buprenorphine retains many of the same risks associated with use of full agonist opioids f or

chronic pain management, yet demonstrates less risk of respiratory depression.

o Risks versus benefits should be assessed periodically throughout treatment.

o Tapering or discontinuing buprenorphine should be considered when risks outweigh benef its

or based on patient pref erence.

o Buprenorphine f or chronic pain should be used at the lowest dose and f or the shortest

duration necessary While evidence supports using buprenorphine for OUD as a

lif elong/lif esaving treatment, the use of buprenorphine f or chronic pain treatment is not

evidence-based.

b. Pain Management Teams (PMT) should be available to provide specialty care support upon request

f or the initiation and stabilization of buprenorphine f or pain.

o Opioid transitions are high-risk, and buprenorphine is no exception.

o Collaboration and co-management can assist with the f requent monitoring indicated, in

particular during transitions to buprenorphine.

c. Screening for and assessment of risk for Opioid Use Disorder (OUD) prior to initiation of treatment is

recommended, and assessment for OUD when patterns of unhealthy medication use (misuse, higher

risk behaviors concerning for OUD) emerge during LTOT. Veterans should be of f ered treatment f or

OUD if appropriate consistent with the VA/DoD Clinical Practice Guideline f or the Management of

Substance Use Disorders (VADoDSUDCPG.pdf)

o Providers should discuss any concerns about increased risk f or OUD, with the Veteran and

caref ully determine if a higher level of care is indicated

o When appropriate, seek consultation with an Addiction Medicine Provider and seek referral to

treatments consistent with VA/DoD Clinical Practice Guideline f or the Management of

Substance Use Disorders

3. B

uprenorphine may be appropriate.

Buprenorphine for Management of Chronic Pain

a. Lack of progress towards f unctional goals and/or inadequate analgesic benef it with f ull mu

agonist opioid

b. High potential f or adverse ef f ects due to medical conditions, mental health or behavioral

considerations with f ull mu agonist LTOT

c. Any transition to buprenorphine, regardless of formulation or f requency, should be considered

only if an around-the-clock opioid therapy is appropriate.

4. Buprenorphine may NOT be appropriate. Clinical situations include:

a. Inf requent use of immediate-release opioid medication for episodic pain (e.g., PRN).

b. Veteran on opioid therapy agreeing to taper or requesting taper (i.e., traditional taper).Utilizing the

existing opioid to taper is preferred and avoids complications of transitions including adverse

ef f ects or concerns f or lack of ef f ectiveness

o Note: transitions to buprenorphine may be reconsidered if

medical/behavioral/psychological concerns emerge during taper

c. Demonstrating f unctional improvement and expressing pref erence to remain on f ull agonist

LTOT, in the absence of medical, mental health, or behavioral risk f or adverse ef f ects

5. D

osage Considerations

Priorities in chronic pain management, even when using buprenorphine, are managing pain to

improve function and quality of life, whereas priorities in managing OUD are more f ocused on harm

reduction. Therefore, the dosages used for treating chronic pain with buprenorphine versus treating

OUD are f undamentally dif f erent. Clinicians selecting buprenorphine primarily f or chronic pain

management should consider the f ollowing:

a) Veterans may stabilize on lower doses of buprenorphine f or pain compared to OUD.

• History of opioid exposure and dosages must be considered when starting buprenorphine

f or pain.

• Clinicians should be responsive and Veteran-centric when making dose titrations since

recommended conversions f or chronic pain are conservative.

• Due to buprenorphine’s long half-lif e, it takes about five days to achieve steady state.

Clinicians should assess the full effect of each dose adjustment when making changes

b) Using the lowest effective dose of buprenorphine for pain that improves function and quality of life

while reduces the risk of dose-dependent adverse outcomes and limits physiologic dependence

c) Veterans displaying higher risk behaviors in the absence of diagnosed OUD, require additional

considerations with transitions to buprenorphine including:

• Prioritizing stabilization or resolution of withdrawal symptoms and discomfort

• Titrating dose slowly toward pain control and f unctional improvement

• Focusing on early recognition of pain reduction and benef its

Note: Low dose buprenorphine is generally not sufficient or appropriate for

treatment of OUD.

6. B

uprenorphine Initiation/Transition Strategies:

a. FDA-approved labeling guidance should be followed in most cases for new starts and standard

opioid transitions to buprenorphine formulations approved for pain, for example patch and buccal

f ilm (e.g., microgram/mcg). Alternatively, low dose initiation (microdosing, overlapping dosing)

may be usef ul f or some Veterans (see below).

o Providers should be aware that published conversion recommendations are highly

conservative (i.e., reduced 50-75%) and already include a reduction f or lack of

tolerance or cross-tolerance

o Providers should avoid rapid titrations without assessing effectiveness and tolerability

at steady state

b. STOP-START method (traditional buprenorphine induction/initiation) is defined as stopping f ull

agonist opioids for 12-24 hours and starting buprenorphine in the early stages of withdrawal. This

decreases risk of precipitated withdrawal and promotes acceptance and quick adjustment to

buprenorphine.

Buprenorphine for Management of Chronic Pain

o This method is quick and generally well tolerated by most Veterans

o It allows f or quick recognition of buprenorphine ef f ectiveness to treat the Veteran’s

pain condition.

c. Low dose buprenorphine initiation (microdosing, overlapping dosing) allows short-term overlap

of buprenorphine titration while on f ull agonist opioid therapy to mitigate withdrawal and

discomfort with transition from full agonist opioid therapy. This strategy may be particularly helpful

for Veterans concerned about experiencing withdrawal and discomf ort.

NOTE: Shared Decision-making and Veteran Preference Should Guide Treatment

Approach

7. For

mulation Guidance by Morphine Equivalent Daily Dose (MEDD):

Care should be individualized for each clinical situation, but if the Veteran is

prescribed:

< 50 MEDD – Buprenorphine formulations FDA-approved f or pain should be considered (mcg

dosing) and either the transdermal patch or buccal f ilms can be utilized

• <30 MEDD – Treat as if opioid naïve and buprenorphine patch is pref erred

• 31-50 MEDD – Buprenorphine onset may be delayed up to 24 hours and not peak for 5 days.

Overlapping with short-acting f ull agonist f or the f irst 24 hours is acceptable

b. 50-90 MEDD – Any available buprenorphine formulation, including the transdermal patch, buccal

f ilms, or buprenorphine SL can be utilized (mcg, mg). Formulation selection will depend on

multiple f actors, please consider the f ollowing:

1) Veterans receiving moderate doses of traditional opioids (50-90 MEDD) who are transitioning to

buprenorphine but are otherwise stable are appropriate f or standard outpatient transitions to

buprenorphine using formulations FDA-approved f or pain specif ically the patch or buccal f ilm

(mcg dosing).

• The buprenorphine buccal f ilm is more appropriate f or moderate MEDD dosing

conversions and allows additional options compared to the patch where utilization is

more challenging at a higher MEDD

• Overlapping buprenorphine strategies or initiation protocols may be usef ul f or moderate

dose conversions to avoid discomfort and aid in pain control during transition to

buprenorphine with both mcg and mg f ormulations.

2) Veterans receiving moderate doses of traditional opioids (50-90 MEDD) who are not stable,

and/or there is concern for potential adverse effects related to behavioral risks in the absence of

diagnosed OUD are appropriate f or conversion to buprenorphine SL (mg). Providers should

f ocus on stabilization and mitigation of withdrawal symptoms and discomf ort in early treatment.

Upon resolution, gradually titrate to therapeutic response and re-evaluate progress toward

f unctional goals in the Veteran’s pain care plan

c. >90 MEDD – Buprenorphine SL (mg) should be considered for Veterans transitioning f rom high

dose opioid therapy. However, Veterans on high dose LTOT of ten stabilize on much lower doses

of buprenorphine compared to those actively using illicit fentanyl or heroin. The use of transition

strategies such as STOP-START or low dose buprenorphine initiation and are likely

recommended. Pain providers should focus on resolving discomfort from acute withdrawals and

then transition to gradually titrating toward improved f unction.

Buprenorphine for Management of Chronic Pain

TABLE 1 – Approximate dose conversion strategies from existing Long-Term Opioid Therapy

<50 MEDD

RECOMMEND: FDA approved

formulations for pain (e.g. mcg dose

transdermal or buccal products)

50 – 90 MEDD

RECOMMEND: All buprenorphine

formulations (mcg or mg) available based

on patient response

>90 MEDD

RECOMMEND:

Buprenorphine milligram

formulations should be

considered

<30 MEDD – Treat as opioid naïve

• Patch is preferred

• 5mcg recommended starting dose

30-50 MEDD –

• Consider 10mcg/hr patch as initial dose

• Onset may be delayed 24 hours

• Overlapping dosing of full agonist opioid

for first 24 hours is reasonable

FDA conversions to buprenorphine are highly

conservative –

• Manufacturer listed conversions already

account for cross-tolerance

• Be responsive during titration phase

Patients who are stable on existing LTOT

• Appropriate for mcg formulations as

initial dose

• Buccal film preferred

• Overlapping strategies may be helpful

Patients with poor function and symptom

control despite existing LTOT (or with concern

for behavioral risks but without OUD)

• Appropriate for consideration of mg

formulations with a focus on early

stabilization of withdrawal symptoms

• Gradual titration to support functional

goals after initial stabilization

• May stabilize on lower doses than

required for OUD.

Early Emphasis on mitigating

withdrawal and discomfort

during the transition from full-

agonist LTOT

Veterans with pain may stabilize

on lower doses that DSM-V O UD

Veteran preference should

guide method of transition

• STOP- START

• Low Dose

Buprenorphine

initiation (LDBI) †

†Example of a 5-day LDBI strategy may be found VA Academic Detailing Buprenorphine for OUD Clinician Guide or Appendix

C below

8. Additional Information:

APPENDIX A: Supplemental Information which Includes: historical background, pharmacology,

clinical trial summary, detailed product inf ormation, additional resource links and bibliographical

reference list

APPENDIX B: Additional Examples of STOP/START or LDBI transitions

APPENDIX C: Flow Chart for reevaluation of LTOT and consideration f or buprenorphine

Updated Mar 2020, May 2022, Oct 2020, Apr 2023, Mar 2024. Initially Prepared: Nov 2019

Contact: Ian W. Pace, Pharm.D. National PBM Clinical Program Manager – Formulary

Acknowledgement: The VHA National Pain Management, Opioid Safety and PDMP Program Office, Dr. Friedhelm Sandbrink

(Director, PMOP), Dr. Tim Atkinson (National PMOP Program Manager), and the Buprenorphine PMOP Subject Matter Expert

Working Group

Buprenorphine for Management of Chronic Pain

APPENDIX A: BUPRENOPRINE -- SUPPLEMENTAL INFORMATION

See the Buprenorphine for Pain Management RFU in above sections for information on the clinical

use of buprenorphine for patients with chronic pain requiring long-term opioid therapy (LTOT) as a

component of their care plan.

Buprenorphine in Pain Management

Several buprenorphine formulation s are FDA-approved for the management of acute or chronic moderate to severe

pain; specifically, buprenorphine solution for injection 0.3mg/ml, buprenorphine transdermal system (5 to 20 mcg/h 7-

day p atch), and buprenorphine buccal film (75 to 900 mcg/film every 12 hours). Numerous safety advantages have

been identified for buprenorphine compared to pure mu agonist opioids including: a ceiling effect on respiratory

depression, less euphoria, reduced tolerance, easier withdrawal, less impairment of cognitive function and

psychomotor activity, lower incidence of constipation, and reduced endocrine and hyperalgesic effects.

Buprenorphine has relatively few drug-drug interactions and does not accumulate in patien ts with renal impairment or

mild/moderate hepatic impairment allowing for use in patients requiring concomitant medications, the elderly, an d

those with renal or hepatic impairment.

1,2

Buprenorphine Clinical Pharmacology in Pain Management

Pharmacologically, buprenorphine’s primary effects are caused by its partial agonism of mu-opioid receptors (MORs)

and antagonism at kappa-opioid receptors (KORs).

Although it has some, but lower, ability to bind to opioid receptor

ligand (ORL)-1 (also known as nociceptin) and delta-opioid receptors (DORs), the clinical effects from these are

negligible.

4-8,

Its traditional categorization as a partial agonist at MORs is primarily due to its lower intrinsic activity

(the biological stimulus a drug has on a receptor) compared to full MOR agonists, as shown mainly in in vitro binding

receptor assay studies.

3-8

This categorizatio n , however, should not be confused with measures of relative clinical

efficacy and potency for an algesia. Several clinical studies have shown th at at low to moderate doses, buprenorphine

can elicit similar analgesic effects compared to equivalent doses of full MOR agonists.

9-17

Its partial agonistic activity

on MORs and antagonistic activity on KORs does allow for a plateauing of the dose response curve (or ceiling effect)

regarding retention of carbon dioxide (as a marker for respiratory depression), thus lowering the risk of overdose

when used without other central nervous system (CNS) depressants.

18-19

Buprenorphine also has one of the highest binding affinities toward MORs compared to all other opioids, the only

exception being naltrexone.

20-21

This strong binding allows buprenorphine to preferentially occupy available MORs

thereby disallowing full agonist opioids to bind, and while this is not a displacement per se, the net effect causes

reversal of opioid activity.

22-23

It also has an extremely slow dissociation rate (the measure of d iseng agement from the

target receptor) from MORs; thus once bound, it is not easily nor quickly displaced.

Buprenorphine in Pain Management: Clinical Trials

Open-label observational studies conducted with relatively small n umbers of patients have reported improved

pain relief on sublingual buprenorphine after conversion from other long-acting opioids.

24-28

One study of 35

patients found a mean decrease in pain score from 7.2 to 3.5, with 34 out of 35 patients reporting a pain

decrease.

A Cochrane meta-analysis found buprenorphine superior to other o pioids for p ain relief in cancer (5

out of 11 studies), equivalent (3 out of 11 studies) or inferior to the alternative treatment (3 out of 11 studies).

The evidence for all the outcomes in the meta-analysis was considered very low quality. One systematic review

which included 10 trials involving 1,190 patients reported that, while all studies demonstrated that subling ual

buprenorphine showed some effectiveness as a chronic pain analgesic, the majority of studies were

observational and of low quality.

In another systematic review which included 25 trials involving 5 different

buprenorphine formulations in patients with chronic pain, a total of 14 of the studies demonstrated clinically

significant benefit.

Only studies with acceptable methodological quality and the low risk of bias were included in

this review. The studies that sh o wed significant reduction in p ain against a comparator included 1 study out of 6

sublingual and intravenous buprenorph ine, th e only sublingual buprenorphine/naloxone study, 2 out of 3 studies

of buccal buprenorp hine, and 10 out of 15 studies for transd ermal buprenorphine. A retrospective chart review

was conducted in 78 patients from a High-Risk Pain Clinic using SL buprenorphine/naloxone (BUP/NAL) plus a

multimodal approach to help chronic pain patients with a history of Substance Use Disorder (SUD) or aberrant

drug-related behavior. The overall retentio n of the High-Risk Pain Clinic was 41%. The mean pain score

demonstrated a significant downward trend across six years of treatment observation (p < 0.001), while the

Buprenorphine for Management of Chronic Pain

opposite trend was seen with buprenorphine dose (p < 0.001) lending support for BUP/NAL as a safe and

efficacious component of comprehensive chronic pain treatment in patients with SUD or high-risk of opioid

overuse or misuse.

Similar positive outcomes were observed in an Opioid Reassessment Clinic (ORC) in a

Veteran s Health Administration hospital for patients with chronic pain treated with opioid regimens d eemed unsafe

by th eir primary care providers. Nearly two -thirds (62%) of those who engaged in the ORC rotated to

buprenorphine as a modality for pain management.

Transitioning veterans presenting with buprenorphine or buprenorphine prescriptions for off-

label indication for pain.

1.35

The Under Secretary for Health’s Information Letter, Access to Medications for Transitioning Service Members,

IL 10-2014-15 (July 7, 2014) and VHA Directive 2014-02, Continuation of Mental Health Medications Initiated by

Department of Defen se Authorized Providers (January 20, 2015) direct providers to carefully evaluate and, unless

medical conditions warrant a change, existing medication therapies should be continued, including

buprenorphine or buprenorphine prescriptions for off-label indication for pain.

PBM Fo rmulary Management - DoD-VA Continuity of Care Drug List -

VA/DoD C

linical Practice Guidelines

36,37

The VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain in general recommends against

initiation of long-term opioid therapy for chronic pain and that non-opioid and non-pharmacologic alternatives

for pain management be part of the treatment plan. In the most recent guideline update, the workg roup made a

recommendation to consider buprenorphine over other opioids when long-term opioid therapy must be co n sid ered.

Pain is a commonly comorbid condition with substance use disorders. Opioid use disorder can similarly occur in

tients treated with long-term opioid therapy for chronic pain. The rates OUD in an LTOT treated chronic pain

population vary widely within published literature.

Nonetheless, If OUD is present, because of the hig h

morbidity and mortality associated with ICD-10 Opioid dependence/DSM-5 Opioid Use Disorder and the

effectiveness of Medicatio n for OUD, providers should be prepared to provide long-term treatment with

buprenorphine. There are many VA resources an initiative directed at provider education regarding the evidence

basted treatment of OUD including:

VA/DoD Clinical Practice Guideline Management of Substance Use Disorder (SUD) 2021

Stepped Care for Opioid Use Disorder - Train the Trainer (SCOUTT)

VHA National Academic Detailing Service -- Opioid Use Disorder Campaign

Buprenorphine – Diagnostic Coding

Prior versions of PBM buprenorphine guidance documents discussed extensively diagnostic criteria related to ICD-10

opioid dependence or DSM-V opioid use disorder (OUD). In part this was because of regulatory requirements

surrounding the X-waiver which was retired as part of the Consolidated Appropriations Act passed in December

2022. As such, in this version we have redacted information pertaining to the diagnosis of OUD and reference the

VA/DoD, Academic Detailing, and SCOUTT initiative resources linked above. With regarding to ICD-10 cod es that

may be utilized in an episode of care where buprenorphine is a part of the care plan the following options are

available:

• F11.1x (opioid abuse) and F11.2x series (opioid dependence) – these sh o uld be utilized wh en the

encounter is for the management of OUD as the primary diagnosis. Use of these codes has the advantage

of ensuring veterans are included in population management dashboards to facilitate best practice care

including medication treatment and harm red uction strategies (e.g. Psychotropic Drug Safety Initiative SUD-

Psychotropic Drug Safety Initiative (PDSI) Management System (sharepoint.com)).

• Z79.891: Long-term (current) use of opioid analgesic – For patients with chronic pain and with

physio logic tolerance/dependence, but without OUD, the primary diagnosis would be the painful condition. If

the encounter of care is primarily for the management of the prescribed opio id, z79.891 is appropriate

• F11.9x series – Internal review suggests this code is being used for a significant minority of patients

prescribed milligram doses of buprenorphine. The clinical scenarios in which this is being used is unknown

at time of update, may represent use of the diagnostically unclear scenario of pain with a dependence or

tolerance that is problematic but is without a concomitant compulsive use component. Is important to be

aware that use of this series DOES NOT INCLUDE patients in th e PDSI SUD 16 population management

dash bo ards for Opioid Use Disorder

Buprenorphine for Management of Chronic Pain

Buprenorphine Dose Equivalence to Morphine

There is wide variability in the reported buprenorphine to morphine equianalgesic ratios with estimated ratios

between 1:10 and 1:100.

The Centers for Medicare and Medicaid Services (CMS) and Center for Disease

Control (CDC) conversion tables

40,41

no longer include a conversion factor for buprenorphine. Similarly, the VA

OTRR, STORM and Academic Detailing reporting tools do not have a conversion or have the conversion factor

calculated as zero. As such, given the wide variability in the recommend ed dose eq uivalen cies between

buprenorph ine and morphine, we are unable to make exact recommendations for equianalgesic dosing.

However, please reference this supplements’ parent document in section above, fo r practical dosing guidance when

converting from existing long-term opioid therapy.

Table 1 -- Buprenorphine Product Comparison Chart

Formulary Buprenorphine Products

Generic

Name

Brand

Name

Formulation

FDA

-Approved Indications

Bioavailability

Elimination

Half-Life

Buprenorphine

Butran s

(VANF)

Transdermal

delivery

system

Available

in 5,

7.5,

10, 15 and

mcg/hr

patches

Max

dose: 20

mcg/hr every

week

Manag ement

of pain severe

enough to require around

the

-clock, long-term opioid

treatment

~15%

~26 hours

Buprenorphine

Belbuca

(VANF)

Buccal film

Available

in 75,

150,

300, 450,

600,

750, 900

mcg

films

Max

dose: 900

mcg

every 12

hours

Manag ement

of pain severe

enough to require around

the

-clock, long-term opioid

treatment

to 65%

11.2

to 27.6

hours

Buprenorphine

and naloxone

sublingual

TABLETS

Suboxone

(VANF)

Sublingual

tablet

Available

in 2-0.5

and 8

-2 mg SL

tabs

main tenance dose

for

OUD is 16 –

24mg/day

Used off

-label for pain

management.

FDA

approved for the treatment

opioid

dependence (a.k.a.

ICD

-10 F11.2x opioid

dependence or DSM

-5

OUD).

~30%

(tab)

~36%

(film)*

to 42

hours

Buprenorphine

sublingual TABLETS

Subutex

(VANF)

Sublingual

tablet

Available

in 2mg

and 8 mg SL

tablets

Target

main tenance

d ose

for

OUD is 16 –

24mg/day

Used off

-label for pain

management.

FDA

approved for the treatment

opioid

dependence (a.k.a.

ICD

-10 F11.2x opioid

dependence or DSM

-5

OUD).

~30%

(tab)

to 42

hours

Buprenorphine for Management of Chronic Pain

Non-Formulary Buprenorphine Products

Buprenorphine

Buprenex

(NF)

IM,

Available

in 0.3

mg/ml

ampules

Dosing:

0.3 mg

every

6-8 hours as

needed

Indicated for the

manag ement

of pain severe

enough

to require an opioid

analgesic and for which

alternate treatments are

inadequate.

100%

1.2

-7.2 hours

(mean

2.2

hours)

Buprenorphine

and

naloxone sublingual

FILMS*

Suboxone

Sublingual Film

(NF)

Sublingual

film

Available

-0.5 4-1, 8-2, and

-3mg film

Target maintenance

dose

for OUD is 16

–

24mg/day

*Th e bioavailability (AUC) of buprenorphine is about 20% greater for buprenorphine with

naloxone 8 mg / 2 mg sublingual film than for the corresponding tablets; but this may not be clinically important

for many

Buprenorphine Injection (BUP INJ). Intended for intramuscular (IM) or intravenous (IV) administration

in the acute setting, BUP INJ was the first buprenorphine product for pain management, launched in the United

States in 1985, and indicated for the management of pain severe enough to require an opioid analgesic and for

which alternate treatments are inadequate.

44, 45

It contains 0.3mg of buprenorphine per 1ml of solution. There are

insufficient data to recommend single doses greater than 0.6mg and the maximum recommended adult dose is

0.6mg admin istered in 6-hour intervals. BUP INJ is not FDA-approved for treatment of opioid dependence/OUD.

Buprenorphine TDS (BUP TDS). BUP TDS is available in 5, 7.5, 10, 15, and 20 mcg/hour patches; the

BUP TDS prescribing information recommends the 5mcg/hr patch as the starting dose for patients on less than

30mg oral morphine equivalents per day while the 10mcg patch is the recommended starting dose for patients on

30-80 mg of daily morphine equivalents.

The TDS product labeling recommends patients be tapered to 30mg o r al

morphine equivalent prior to initiating therapy with BUP TDS 10 mcg/hour. However, this may not be practical for all

patients and the Buprenorphine in Chronic Pain guidance document provides alternate conversion strategies that can

be co n sidered. Dose adjustments should not be made until at least 72 hours of use at the same strength since it

takes approximately 72 hours to ach ieve stead y state concentrations. BUP TDS h as an apparent terminal half-life

of 26 hours. BUP TDS may be a viable option in those patients who cannot tolerate the oral route of

administration, as well as in the geriatric population who are more susceptible to the adverse reactions related to

other opioids. BUP TDS may also be a good option for use in patients where there are concerns with the

prescription of oral opioids. BUP TDS may not provide adequate analgesia for patients requiring greater than 80

mg of morphine equivalents per day. BUP TDS is not FDA-approved for treatment of opioid dependence/OUD.

Buprenorphine Buccal Film (BUP BF). BUP BF is available in 75 mcg, 150 mcg, 300 mcg, 450 mcg,

600 mcg, 750 mcg, an d 900 mcg dosage strengths. Opioid-naïve patients may be started at 75 mcg once daily or

every 12 hours but starting doses for the opioid-experienced patient are based on th e d aily morphine equivalent

dose when converting from other opioids to BUP BF. As with BUP TDS and per BUP BF prescribing information,

patients must be tapered to 30mg oral morphine equivalent or less prior to initiating therapy with BUP BF. Two

12-week, multicenter, Phase III studies, one in opioid-naïve and one in opioid-experienced patients, were able to

demonstrate statistically significant reductions in pain scores in patients with chronic low back pain with BUP BF

when compared with placebo.

47, 48

BUP BF may not provide adequate analgesia for patients requiring greater

than 160 mg oral Morphine equivalent daily dose (MEDD); consider the use of an alternate analgesic.

BUP BF

is not FDA-approved for treatment of opioid dependence/OUD.

Buprenorphine (BUP) and Buprenorphine/Naloxone (BUP/NAL). BUP/NAL was approved by the

FDA in 2002 for treatment of opioid dependence (a.k.a. DSM-5 OUD)

but is sometimes prescribed off-label for

chronic pain management.

Possible mechanisms for pain relief by BUP/NAL include reversal of opioid induced-

hyperalgesia and improvement in opioid dependence symptoms.

51-53

One randomized controlled clinical trial

demonstrated the efficacy of BUP/NAL fo r pain management in patients being treated for opioid use disorder

Buprenorphine for Management of Chronic Pain

(OUD).

Current data suggest that buprenorphine may provide pain relief in patients with chronic pain and

opioid use disorder, but the data for patients without opioid use disorder is observational, retrospective only so

difficult to draw conclusions from.

51-59

At time of document update, a prospective trial looking at use of milligram

doses of buprenorphine in a high-dose opioid chronic pain population was still ongoing (personal communication,

Krebbs 2024).

A Cochrane meta-analysis fo un d bup renorphine superior to o ther opioids (5 out of 11 studies),

equivalent (3 out of 11 studies) or inferior to the alternative treatment (3 out of 11 studies) for pain relief in

can cer.

The evidence for all the outcomes in this meta-analysis was considered very low quality. One

systematic review which included 10 trials involving 1,190 patients reported that, while all studies demonstrated

that sublingual buprenorphine showed some effectiveness as a chronic pain analgesic, the majority of studies

were observational and of low quality.

A retrospective cohort study in a VHA hospital Opioid Reassessment

Clinic (ORC) demonstrated the feasibility of rotating patients on long-term opioid therapy for pain to BUP/NAL.

Further research is needed to demonstrate the efficacy of BUP/NAL for pain in patients with and without opioid

dependence/OUD.

Buprenorphine for OUD During Pregnancy/Breastfeeding

Although this document is focused on the use of buprenorphine in chronic pain conditions, worth noting that the

prevalence of OUD during pregnancy more than d oubled between 1998 and 2011 to 4 per 1000 deliveries and is

increasing.

61, 62

Evidence-based clinical guidance on the treatment of these women and their children are needed

given that women with OUD have a higher frequency of additional risk factors for adverse pregnancy outcomes than

do pregnant women who do not use o p ioids. A literature review to support National guidance was commissioned by

SAMHSA to obtain curren t evidence on treatment ap proaches for pregnant and nursing wo men with OUD and their

infants and children.

The report concluded that the accep ted treatment for OUD durin g p regnancy is long-acting

opioid agonist MAT that includes methadone or buprenorphine provided within the context of a comprehensive

program of obstetrical care and behavioral intervention. In addition, breastfeeding among women not using other

substances and maintained on methadone or buprenorphine can encourage and promote maternal-infant bonding,

and likely have mitigating effects on Neonatal Abstinence Syndrome (NAS) severity. The Maternal Opioid

Treatment: Human Experimental Research (MOTHER) project found that neonates of mothers treated with

buprenorphine d uring pregnancy required significantly less morphine, had a significantly shorter hospital stay, and

had a significantly shorter duration of treatment for the neonatal abstinence syndrome, as compared to neonates

whose mothers were treated with methadone.

The American College of Obstetricians and Gynecologists (ACOG)

recommends opioid agonist pharmacotherapy in pregnant women with an OUD as preferable to medically

sup ervised withdrawal which is associated with higher relapse rates and worse outcomes.

ACOG also

enco urages breastfeeding in women who are stable on their opioid agonists and are not using illicit drugs or have

any contraindications such as human immunodeficiency virus (HIV) infection. Because of the low levels of

buprenorphine in breastmilk, its poor oral bioavailability in infants, and th e low drug concentrations found in the

serum and urine of breastfed infants, the NIH Drugs and Lactation Database (LactMed) database reports the use of

buprenorphine as acceptable in nursing mothers.

Additional Considerations

QTc Monitoring. Buprenorphine mildly inhibits cardiac repolarization and has been noted to prolong the

QT interval when the tran sdermal patch is administered at doses greater than 20mcg/hour.

23,30

Per BUP TDS

prescribing information , the effect of BUP TDS 10 mcg/h o ur and 2 x BUTRANS 20 mcg/hour on QTc interval was

evaluated in a double-blind (BUP TDS vs. placebo),

Buprenorphine for Management of Chronic Pain

Table 2 -- Buprenorphine for Chronic Pain Comparison Chart

27,29,30,33,44

(See Appendix C for

Buprenorphine for Pain Management Algorithm).

Topic

BUP TDS

(BUTRANS)

BUP Buccal Film (BF)

(BELBUCA)

BUP and BUP/NAL

(SUBOXONE, generics)

Recommended

Conditions

for Use

in Pain

Management

Indication is management o f moderate to

severe chronic pain requiring a

continuous, around-the-clock opioid

analgesic for an extended period of time

AND

The patient is assessed as high risk for

traditional oral opioid therapy and alternate

buprenorphine products are not advisable.

Indication is management o f moderate to

severe

chronic pain requiring a

continuous, around

-the-clock opioid

analgesic for an extended period of time

AND

The

patient is assessed as high risk for

traditional oral opioid therapy and alternate

buprenorphine products are not advisable.

BUP and BUP/NAL SL tablets

are

indicated for the induction

and

maintenance treatment of

opioid dependence (ICD

-10,

a.k.a. OUD).

BUP

and BUP/NAL may be used

any DEA licensed provider for

pain management and comorbid

opioid

dependence/OUD.

Patient has documented difficulty

swallowing, poor or unpredictable

gastrointestinal absorption (e.g., short

bowel; nausea, vomiting).

Patient has documented

difficulty

swallowing,

poor or unpredictable

gastrointestinal absorption (e.g., short

bowel; nausea,

vomiting).

BUP TDS 20 mcg/hour may not provide

adequate analgesia for patients requiring

greater than

80 mg/day oral morphine equivalents.

Consider the use of an alternate analgesic

or, if buprenorphine is required, consider

the use of BUP BF.

BUP BF may not provide adequate

analgesia for patients requiring greater than

160 mg/day oral morphine equivalents.

Consider the use of an alternate analgesic

or, if buprenor

phine is required, consider

referral to an x

- waivered provider for

consideration

of buprenorphine

buprenorphine/naloxone Sublingual

tablet.

Considerations for

Use

•

Because of the risks of addiction,

abuse, a nd misuse with opioids, even at

recommended doses, and

because of the greater risks of overdose

and death with extended-release

opioid formulations, reserve BUP

TDS for use in patients for whom

alternative treatment options (e.g.,

non-opioid analgesics or immediate-

release opioids) are ineffective, not

tolerated, or would be oth erwise

inadequate to provide sufficient

manag ement of pain.

• BUP TDS is not indicated as an

as-needed (prn) analgesic.

• Instruct patients to wear BUP TDS

for 7 days and to wait a minimum

of 3 weeks before applying to the

same site.

• Do not abruptly discontinue BUP

TDS in a physically dependent

patient.

• Allow 3 days on current dose to

evaluate the full therapeutic effect

prior to making additional dosage

adjustments

Do not apply direct heat

•

Because of the risks of addiction,

abuse, and misuse with opioids, even

at recommended doses, and

because

of the greater risks of overdose

and death with

extended-release

opioid formulations, reserve BUP BF

for use in patients for

whom

alternative

treatment options (e.g.,

non

-opioid analgesics or immediate-

release opioids) are ineffective,

not

tolerated,

or would be otherwise

inadequate to provide sufficient

manag ement of

pain.

• BUP BF is not indicated as an as-

needed (prn) analg esic.

• To be prescribed only by health

care providers knowled g eable

in use of potent opioids for

management of chronic pain.

• Use the lowest effective dosage

for the shortest duration

consistent with individual patient

treatment go als

Individualize

dosing based on the

severity of pain, patient response,

prior analgesic

experience, and risk

factors for addiction, abuse, and

misuse

BUP sublingual tablet

contains

no naloxone and

may be preferred during

pregnancy,

BUP/NAL sublingual tablet

is preferred

for mo st

patients,

but especially if

there

are concerns for

misuse or diversion.

If used for pain in a patient

without ICD

-10 opioid

dependence, the encounter

should indicate the pain

condition diagnosis, the

prescription

should state “for

pain management”

Buprenorphine for Management of Chronic Pain

Considerations for

Use (Continued)

extended-release opioid

formulations, reserve BUP TDS for

use in patients for

whom alternative

treatment

options (e.g., non-opioid

analgesics o r immediate

- release

opioids) are ineffective,

not tolerated,

or would be otherwise inadequate to

provide sufficient management of

pain.

• BUP TDS is not indicated as an

as-needed (prn) analgesic.

• Instruct patients to wear BUP TDS

for 7 days and to wait a minimum

of 3 weeks before applying to the

same site.

• Do not abruptly discontinue BUP

TDS in a physically dependent

patient.

• Allow 3 days on current dose to

evaluate the full therapeutic effect

prior to making additional dosage

adjustments

• Do not apply direct heat

extended-release opioid formulations,

reserve BUP BF for use in patients for

whom

alternative treatment options

(e.g., non

-opioid analgesics or

immediate

- release opioids) are

ineffective,

not tolerated, or wo uld be

otherwise inadequate to provide

sufficie

nt management of pain.

• BUP BF is not indicated as an as-

needed (prn) analg esic.

• To be prescribed only by health

care providers knowled g eable in

use of potent opioids for

management of chronic pain.

• Use the lowest effective d osag e for

the shortest duration consistent

with individual patient treatment

goals

• Individualize dosing based on the

severity of pain, patient response,

prior analgesic experien ce, an d risk

factors for addiction, abuse, and

misuse

BUP sublingual tablet

contains

no naloxone and

may be preferred during

pregnancy,

BUP/NAL sublin gual tablet is

preferred

for mo st patients,

but especially

if there are

concerns for misuse or

diversion.

• If used for pain in a

patient without ICD-10

opioid dependence,

the encounter should

indicate the pain

condition diagnosis,

the prescription should

state “for pain

manag ement”.

Baseline

Evaluation

Urine drug screen (UDS)

Prescription

Drug Monitoring

Program (PDMP) Check

Liver tran saminases

Monitor for

effectiveness

pain

relief

Assess patient’s risk for physical or

psychological

dependence, drug

diversion

and sensitivity to adverse

effects, particularly respiratory

depression

Assess mental status,

respiratory

status, and increased

risk

for falls.

Urine drug screen (UDS)

Prescription

Drug Monitoring Program

(PDMP) Check

Liver tran saminases

Monitor for

effectiveness

pain

relief or prevention of

opioid

withdrawal symptoms Assess

patient’s risk for

physical

or psychological

dependence,

drug diversion and

sen sitivity to adverse effects, particularly

respiratory depression

Assess mental status, respiratory

status,

and increased risk for falls.

Urine drug screen (UDS)

Prescription

Drug Monitoring

Program

(PDMP) Check

Liver

transaminases

Urine beta

-HCG for

females Monitor

for

effectiveness

of pain

relief

or prevention of opioid

withdrawal

sympto ms

Assess

patient’s risk for

physical or

psychological

dependence, drug diversion

and sensitivity to

adverse

effects,

particularly

respiratory depression

Assess

mental status,

respiratory

status, and

increased risk for falls.

Buprenorphine for Management of Chronic Pain

Dosage and

Administration

BUP TDS doses of 7.5, 10, 15,

and 20 mcg/hour are for opioid

exp erienced

patients only.

For

opioid-naïve patients, initiate

with

a 5 mcg/hour patch.

Each BUP TDS patch is intended

worn for 7 days.

• *Conversion from Oth er

Opioids to BUP TDS

Discontinue all other around-

the-clock opioid drugs when

BUP TDS therapy is in itiated.

• There is a potential for

uprenorphine to precipitate

withdrawal in patients who are

already on opioids.

Prior Total Daily Dose of Opioid

Less

than

30 mg of Oral Morphine

Equivalents

per Day:

• Initiate treatment with BUP TDS 5

mcg/hour at the next dosing

interval

Prior Total Daily Dose of Opioid

Between

30 mg to 80 mg of Oral

Morphine Equivalents per Day:

• Taper the patient’s current

around-the-cl ock opioids for up to

7 days or more as tolerated by

the patient, to no more than 30

mg of morphine or equivalent per

day before beginning treatment

with BUP TDS.

• Then initiate treatment with BUP

TDS 10 mcg/hour at th e n ext

dosing interval

• Patients may use short- acting

analgesics as needed until

analgesic efficacy with BUP

TDS is attained.

Prior Total Daily Dose of Opioid

Greater than 80 mg of

Oral Morphine

Equivalents

per Day:

• BUP TDS 20 mcg/hour may not

provide adequate analgesia for

patients requiring greater than 80

mg/day oral morphine

equivalents. Co n sid er the use of

an alternate an algesic.

If the patien t experiences problems

with

adhesion, the patch may be

secured

with a transparent adhesive

film dressing such as Teg aderm™.

BUP BF is for oral buccal use

only and is to be applied to

the buccal

mucosa

every 12 hours.

*Discontinue all other around

- the-clock

opioid

drugs when BUP BF therapy is

initiated.

For

the Opioid-Naïve or Opioid Non-

Tolerant patient.

• Initiate treatment in opioid- naïve

and opioid-non-

tolerant

patients with a 75 mcg film

once daily or, if

tolerated, every 12

hours for at least 4 days, then increase

dose

to 150 mcg every 12 h o urs.

• Individual titration to a dose that

provides adequate analgesia and

min imizes adverse reactions should

proceed in increments of 150 mcg

every 12 hours, no more frequently

than every 4 days.

• Doses up to 450 mcg every 12 ho urs

were studied in opioid-n aïve

patients in the clinical trials; use of

higher starting doses in patients

who are not opioid tolerant may

cause fatal respiratory depression.

Conversion from other Opioids to BUP

• There is a potential fo r

buprenorphine to precipitate

withdrawal in patients who are

already on opioids. To reduce the

risk of opioid withdrawal, taper

patients to no more than 30 mg oral

MEDD daily before beginning BUP

• Initial BUP BF dose based on prior

opioid expressed as oral MEDD

- Less than 30 mg oral MEDD ;

BUP BF 75 mcg

or q 12 hours

- 30 to 89 mg oral MEDD ;

BUP

BF 150 mcg q 12

hours

- 90 to 160 mg oral MEDD

;

BUP BF 300 mcg q 12

hours

> than 160 mg oral MEDD ; consider

alternate

analgesic.

For patients on BUP/NAL for

ICD

-10 opioid

dependence/OUD

. The

current

24-hour dose of

BUP/NAL

can be split and

divided for BID or TID dosing

for pain

manag ement.

When initiating BUP/NAL

for

patients who do not meet

ICD

-10 definition of opioid

dependence

but who are not

appropriate for

BUP TDS or

BUP BF

Opioids should be

discontinued the

day prior,

and

the patient sho uld be in

mild withdrawal prior to

initiation of BUP or

BUP/NAL

The most common dose

prescribed in VHA is

16mg/day. Primarily for

OUD. Doses of BUP or

BUP/NAL necessary for

long

-term opioid therapy

as part of a chronic pain

are not well known. In

general a starting dose of

2mg to 4mg may be

adequate with dose

adjustm

ent initially

Alternatively, patients with

mod erate

to severe

withdrawal symptoms

(COWS*

score > 8) may

require bup renorphin e

induction with stabilization at

the lowest effective dose that

controls

withdrawal

symptoms and minimizes

side effects.

The need

for higher doses is

determined

by the function

and clinical status of the

patient, optimally following a

shared decision

-making

model.

*COWS

= Clinical Opioid

Recommendation to taper to <30mg MEDD (BUP TDS and BUP BF) or interrupting opioid therapy until withdrawal

symptoms occur (BUP or BUP NAL) may not be required or realistic in all patients. See

Appendix B for alternate

initiation and dose conversion strategies

See individual product prescribing information for Contraindications, Warnings/Precautions, Dosing in Special

Populations, Major and Common Adverse Effects, Drug Interactions, and

monitoring.

Buprenorphine for Management of Chronic Pain

Discontinuation and

tapering

guidance

A decision to discontinue BUP

TDS after a period of therapy

sh o uld be part

of a

co mprehensive treatment

plan. There is in sufficient

data to determine the best

method

of dose taper at the

end of treatment. For BUP

TDS, it is reasonable to

consider reducing the dose by

5mcg/hour every 2 to 4

weeks

until

the 7.5mcg/hour dose is

reached; BUP TDS may be

discontinued

thereafter

A decision to discontinue BUP BF

after

a period of therapy should be

part of a comprehensive treatment

plan. There is in sufficient

data to determine the best method

dose

taper at the end of treatment.

For BUP BF, as with other full mu

agonists,

it is reasonable to consider

reducing the dose by 5 to

20% every

4 weeks for

a slow taper, or 5 to 20%

every week for a faster taper. See

the Academic Detailing

Opioid

Taper

Decision Tool

for more guidance

A decision to discontinue SL

BUP o f BUP/NAL after a

period of therapy should be

part of a

comprehensive

treatment p lan. There is

insufficient data to determine

the

best method of dose taper

Patient Education

See BUP TDS Prescribin g

Information

for full patien t

counselling guidance.

Advise patients of the

addiction,

abuse and misuse

potential of BUP TDS, the

risks for life threatening

respiratory depression,

acciden tal exposure

(especially in children),

interaction with alcohol and

other

CNS depressan ts, risk

for Neonatal Opioid

Withdrawal Syndrome, side

effects

such as constipation,

and caution with driving or

operating

heavy machinery.

Advise

patients on the proper

administration and

application of the patch,

application site rotation,

disposal, and to not apply

direct heat.

BUP

TDS should be stored

and

kept o ut of sight and

reach of children.

See BUP BF Prescribin g Information

for

full patient counselling guidance.

Advise patients of the addiction,

abuse

and misuse p otential of BUP

TDS, the risks for life threatening

respiratory depression, accidental

exp o sure (especially in

children),

interaction with alcohol and other

CNS

dep ressants, risk for Neonatal

Opioid Withdrawal Syndrome, side

effects

such as constipation, and

caution with driving or operating

heave

machinery.

Instruct patients how to

pro p erly use BUP BF,

including

the

following:

• To carefully follow instructions

for the application of BUP BF

and to avoid eating or drinking

until it dissolves.

• Advise patients that, after

BUP BF has comp letely

dissolved in the oral mucosa,

to take a sip of water, swish it

gently around their teeth and

gums, and swallow. Advise

patients to wait for at least one

hour after taking BUF BF

before brush ing teeth.

Instruct patients to inform their

dentist that they h ave started

therapy on BUF BF.

• To apply BUP BF once daily,

or every twelve (12) hours at

the same time or times each

day.

• To avoid applying BUP BF to

areas of the mouth with any

open sores or lesions.

• To not use BUP BF if the

pouch seal is broken or the

buccal film is cut or

damaged

See BUP an d BUP/NAL

Prescribing

Information for full

patient

counselling guidance.

Discuss

methods to

enhance medication

adherence

Negotiate

patient’s commitment

to monitored ingestion

The pill is taken once a day

under the tongue, allow

dissolving,

do NOT ch ew or

swallow.

Sto re

in secure place out of the

reach of children.

Adverse effects, if any, are

usually

mild and go away after

the

medication has been taken

for a while. If you have side

effects you should NOT abruptly

stop taking your medication,

instead, talk to your doctor

about it.

• Advise patients that, after

BUP o r BUP/NAL h as

completely dissolved in

the oral mucosa, to take a

sip of water, swish it gently

around their teeth and

gums, and swallow.

Advise patients to wait for

at least one hour after

taking BUF/NAL before

brushing teeth.

Instruct patients to inform their

dentist

that they have started

therapy on BUP/NAL

Buprenorphine for Management of Chronic Pain

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Buprenorphine for Management of Chronic Pain

APPENDIX B – EXAMPLES OF TRANSITION STRATEGIES FROM

LONG-TERM OPIOID THERAPY (LTOT) TO BUPRENORPHINE

Buprenorphine for Management of Chronic Pain

APPENDIX C – FLOW CHART TO FACILITATE CLINICAL DECISION

MAKING FOR CONSIDERATION OF BUPRENORPHINE FOR LONG-

TERM OPIOID THERAPY (LTOT)

*NOTE: The clinical determination of functional status and assessment of benefits vs. risks, especially in context of

what may be years of LTOT for chronic pain, can often be diagnostically challenging. Facility Pain Management

Teams (PMTs) and/or VISN Clinical Resource Hubs are available to assist with both the evaluation of and treatment

planning for veterans with chronic pain on LTOT (or LTOT taper).

†

ADDITIONAL CONSIDERATIONS – There is no definition of “doing well” or “not doing well with LTOT.” The 2022 CDC and VA/DoD clinical

practice guidelines on opioid therapy

1,2

both recommend evaluating function to determine benefit of LTOT. No specific or preferred means to do

this are described and, although rating scales, qualitative interviews, clinical judgment, shared decision-making, etc. can all be used, there is no

evidence base to support use of any approach as better than another. The 2023 NICE safe prescribing guidelines for medicines associated with

dependence or withdrawal recommend evaluating on risks and benefits similarly without any specific means of how to do so.

Manhapra and

colleagues recently suggested using function compared to an age related peer and presence or absence of high-risk events (or future risk of high-

risk events) as at least a practical starting point to evaluate functional benefit of LTOT in setting of chronic pain

and during the PMOP

Buprenorphine SME workgroup there was general agreement that approaching the assessment of how a veteran is doing should be consistent

with Whole Health Principles (e.g. Personal Health Inventory, Wellbeing Signs may be helpful).

Until an evidence base or specific guidance

exists to provide clarity on best means of evaluating the functional benefit of LTOT, VHA local pain management teams, VISN Telepain teams,

and PMOP initiative resources are available to assist with care planning for the veteran with chronic pain on LTOT. Additional resources may be

found here VHA Pain Management, Opioid Safety, and Prescription Drug Monitoring Program (PMOP) (sharepoint.com)

1. CDC Clinical Practice Guidelines for Prescribing Opioids MMWR 2022; 2. VA/DoD Clinical Practice Guideline: The Use of Opioids in the Management of Chronic

Pain 2022 Accessed Jan 2024; 3. National Institute for Health Care Excellence NICE: Prescribing medications associated with dependence or withdrawal -- 2023; 4.

Manhapra, A. et. al., Are Opioids effective analgesics and is physiological opioid dependence benign? Revising current assumptions to effectively manage long-term

opioid therapy and its deprescribing Brit J Clinical Pharma 2023 1-

15; 5. PMOP Buprenorphine Subject Matter Experts Guideline development sequester and

document draft meeting, Fall 2023