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Buprenorphine and Naltrexone

Induction

J. Deanna Wilson, MD, MPH

University of Pittsburgh School of Medicine

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Disclosures

J. Deanna Wilson, MD, MPH

No Disclosures

The content of this activity may include discussion of off label or investigative drug uses.

The faculty is aware that is their responsibility to disclose this information.

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Target Audience

• The goal of PCSS is to train a diverse

range of healthcare professionals in the

safe and effective prescribing of opioid

medications for the treatment of pain, as

well as the treatment of substance use

disorders, particularly opioid use

disorders, with medication-assisted

treatments.

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Educational Objectives

• At the conclusion of this activity participants should

be able to:

Identify different models for induction of

buprenorphine and naltrexone in the outpatient

office setting

Explain the goals for office-based induction

List key strategies for managing precipitated

withdrawal

Describe medications to support successful

induction of naltrexone for opioid-dependent

patients

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Thomas Is A 22 y.o. Who Presents

For First Visit

• Thomas reports a history of opioid use, started at age 16 after receiving first opioid prescription following dental extraction

• Reported misuse initially with prescription opioids, transitioned to nasal and later injection heroin

• Uses up to 10 bags a day of heroin with last use about 4 hours ago

• Has attended multiple inpatient rehabs and intensive outpatient programs but never taken medication to treat opioid use disorder as outpatient

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Thomas

• His mother came with him today

• His plan is to stay with her for the next few weeks

until he gets back on his feet

• Denies any withdrawal symptoms currently and

reports withdrawal symptoms usually start about 8-12

hours after his last dose of heroin

• Has friends who did well on buprenorphine and he

tried it once or twice while having withdrawal

symptoms

• He would like to start treatment as soon as possible

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What Options Are Available to Treat

Thomas?

Office-based induction

Provide medication from office stock

Provide prescription to patient to fill and bring for

observed administration in office

Home-based induction

Provide education on induction protocol

Give prescription for initiation of buprenorphine

unobserved at home

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Goal of Induction

Find dose that:

Suppresses opioid withdrawal symptoms

Has minimal or no side effects

Decreases cravings

Markedly reduces use of other opioids

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Preventing Precipitated Withdrawal

• Avoid precipitated withdrawal by starting induction when

patients no longer have opioid agonists in system

Use Clinical Opioid Withdrawal Scale (COWS)

− Ideally >10 score

• Assess last dose of short- and long-acting opioids

Use evidence of withdrawal (time from last dose less

important than presence of subjective withdrawal criteria)

Abstinence from:

− Short-acting opioids: 12-16 hours

− Medium-acting: 17-24 hours

− Methadone: 36-72 hours

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Typical Office-based Induction

• Patients present in withdrawal for first visit and same-day

induction or should schedule second follow-up visit for

induction

• During induction visit:

Should report abstinence from opioids for:

− 12-24 hours for short-acting opioids, like heroin

− 32-72 hours for methadone

Document opioid withdrawal symptoms prior to dosing

− Uses Clinical Opioid Withdrawal Scale

− Should be in mild to moderate opioid withdrawal,

although no clear parameters (12-16 COWS target)

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Clinical Opioid Withdrawal Scale

11-item scale to stage severity of opioid withdrawal

Points for severity within each category

5-12=mild; 13-24=moderate; 25-36=moderately severe;

more than 36 is severe withdrawal

Categories:

Resting pulse rate

Sweating

Restlessness

Pupil size

Bone or joint aches

Runny nose or tearing

GI upset

Tremor

Yawning

Anxiety or irritability

Gooseflesh skin

Wesson & Ling, 2003.

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Typical Office-based Induction

• Administer 2-4 mg buprenorphine/naloxone dose, monitor

patients over a 1-2 hour period

• Re-dose buprenorphine/naloxone as needed

− Dosing every 1-2 hours for persistent withdrawal

symptoms

− Varied approaches use maximum day dosing of 8-16 mg

• Challenges:

Regulations related to in-clinic

dispensing of controlled

substances

Waiting area logistics

Time intensive

Casadonte, 2013.

Nielsen, 2014.

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Typical Home Induction

• Evaluated prior to beginning treatment, typically while using opioids

Medical, psychiatric, substance use assessments

Laboratory testing

Urine drug testing

Given prescriptions for buprenorphine

• Patients given instructions on induction protocol

Decide when to discontinue misuse

How to monitor for signs/symptoms of withdrawal

How and when to take initial dose of buprenorphine

When and who to contact with problems

• Advantages

Potential time-saving

Safe

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Office vs. Home Induction

Limited data on head to head comparisons

Similar rates treatment retention

Feasible with low rates of adverse events

• Limited reports of precipitated withdrawal

• No serious adverse events

Similar drop-out rates

Limited comparison trials to compare efficacy as most predominantly observational

Sohler, et al, 2010.

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Review of Literature

• Literature review of studies focused on home induction

10 clinical studies included

− 1 randomized controlled trial

− 3 prospective studies

− 6 retrospective studies

• Weak to moderate support showing no differences in adverse

event rates between observed and unobserved inductions

• Insufficient or weak evidence in terms of any or no differences in

overall effectiveness

Need more research!

Lee, et al, 2014.

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Thomas

• You discuss the various options for induction,

including pros/cons of each

• He prefers to do home induction

What are your instructions to him?

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Sample Protocol; Lee, Et Al 2009

• Instruct patients to take first 4 mg buprenorphine dose with 1-2

additional doses every 1-4h for a maximum daily total of 12 mg

Typically 14 8mg/2mg buprenorphine/naloxone tablets/films

issued

• Subsequent 4 mg incremental adjustments on day established

dose

• Utilize teach-back on how initiate induction

• Instructed to call physician or clinic coordinator during day 1-3

of induction and return for follow-up at 7 days

Lee, 2009.

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Lee, 2009.

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Lee, 2009.

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Lee, 2009.

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Lee, 2009.

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Thomas

Thomas “teaches back” instructions for induction

• Given prescription for 14 8/2 mg buprenorphine/naloxone films

• Waits until he has withdrawal symptoms and takes 4 mg of

buprenorphine

• Still having withdrawal symptoms after 2 hours and takes

another 4 mg dose

• Withdrawal symptoms disappear after 3rd dose of

buprenorphine

• Feels good when he wakes up on Day 2 and takes 12 mg of

buprenorphine/naloxone in the morning

• Follows-up a week later and returned 7 strips that were unused

• Given a regular maintenance prescription of 12 mg per day

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• He has been taking methadone 90 mg a day for the past 7

years

• He last used heroin about 7 ½ years ago. Used for

approximately 6 years. Denies any cravings.

• He got a new full-time position working with food service at

your hospital system

• He has to be at work early in the morning and hopes to switch

to buprenorphine-naloxone for greater flexibility

What guidance do you give him?

Nicholas

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Transitioning From Methadone

• Should be tapered from regular daily dose to no more than 30 mg a day for week prior to transition

• Has higher risk for precipitated withdrawal and so may consider doing office-based induction

• Ask patients to hold methadone dose for 48-72 hours

• Only start buprenorphine when experiencing moderate withdrawal symptoms

COWS 13-15

• May need higher doses of buprenorphine for induction

• Higher rates of prolonged spontaneous opioid withdrawal

Characterized by anxiety, nausea without vomiting, sweating, musculoskeletal aches, sleepiness/sedation

• Prepare patients transitioning from methadone for potential discomforts of prolonged withdrawal

Lee, 2014.

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Nicholas

• Nicholas is tapered down over a two-week period from 90 mg

to 30 mg of methadone a day. He stays at 30 mg a day of

methadone for the next week

• Abstains from methadone for 48 hours and comes to see you

in clinic

• Has moderate withdrawal symptoms characterized by a

COWS score of 14

• Receives 4 mg of buprenorphine and experiences increased

worsening of withdrawal symptoms within 30 minutes of first

dose

Becomes febrile and tachycardic with severe diarrhea,

vomiting, and muscle cramps

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Treat Precipitated Withdrawal

• Goal is prevention, although not always easily avoidable

• Treatment is symptomatic and patient-driven

• Use medications to treat symptoms (nausea, diarrhea, muscle

pain, adrenergic activity)

• Continue to treat withdrawal symptoms with additional

buprenorphine

Additional small doses of buprenorphine to fill mu opioid

receptors

May need higher overall daily amount of buprenorphine to treat

through

Give buprenorphine dose in small 2 mg increments

• Ideal to continue to induct on buprenorphine if possible

Rosado, 2007.

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Nicholas

• Given loperamide and ondansetron

• Also receives 2 mg of buprenorphine every hr for

the next 4 hours until he reports overall

improvement in his symptoms

• Receives 4 mg dose of bup in your office and an

additional 4 mg dose at home before bed for

ongoing withdrawal symptoms

• Total daily dose on day 1 was 20 mg

• Next day reports some ongoing mild withdrawal

symptoms and is started on 24 mg a day of

buprenorphine/naloxone

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Jane, 49 Y.O. Presents for First

Visit

Jane has a history of heroin use (injected about 8-12 bags a day for about 10 years) prior to incarceration

Reports undergoing severe opioid withdrawal during her incarceration, has not used since

Was released 45 days ago and while her last heroin use was about 4 ½ years ago, she started having cravings when she drove by where she used to obtain heroin

Having increased intrusive thoughts about using heroin, wants to start medication to help manage her cravings

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Jane

Detailed review of her history shows she meets DSM-5 criteria

for severe opioid use disorder

• Her POC urine is negative for opioids and any illicit

substances

• Her PDMP is negative for any opioid medications

What options are available to treat

Jane?

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Induction Options if Not Currently

Dependent on Opioids • Common scenarios:

Post-supervised withdrawal/“detoxification”

Post-incarceration

Post-hospitalization

• All options of treatment are available Full agonists/partial agonists

− Do not have to worry about precipitated withdrawal risk for partial agonists

− Should “start low and go slow”

Antagonists

− Many times an ideal window to start as no need for several days of abstinence before starting

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Jane

What do you tell Jane?

• Jane elects to start buprenorphine/naloxone

• She is started on 12 mg a day (a dose that manages her

cravings)

• She does well for 9 months and then, after receiving an opioid

prescription for a dental procedure, reports having relapsed

• She stopped her buprenorphine/naloxone (last took about 3

weeks ago), and has been using intermittent heroin for about 2

½ weeks. Her last use was 2 days ago

• She reports moderate withdrawal symptoms

• She wants to get back on treatment, but would prefer to start

taking the “opioid blocking medicine” she has heard about

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Approach to Naltrexone Induction

• If no opioid use for greater than 14 days

Have supporting evidence of no use

Give XR-naltrexone injection

• If opioid use within 7-14 days

Evaluate for withdrawal symptoms

If withdrawal symptoms present

− Treat symptomatically

− Recheck in 1-2 days

If no withdrawal symptoms present

− CHALLENGE

– IM naloxone or po naltrexone

– If successful, then XR-Naltrexone injection

• If opioid use within 7 days

Treat with supportive medications

Wait until 7 days of no use to challenge

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Sample Medications for Symptomatic

Withdrawal Management • Autonomic arousal

Clonidine (0.1 mg po q8h)

• Anxiety/restlessness

Hydroxyzine (25-50 mg po q6-8h)

• Insomnia

Trazodone (50-100 mg po qhs)

• Musculoskeletal pain

Ibuprofen (600 mg po q4-6h)

• GI distress

Ondansetron (4-8 mg po)

Loperamide (2 mg po following each bowel movement)

− Daily maximum no more than 16 mg

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Challenge Procedures

• I.M. Naloxone Challenge Procedure

Obtain baseline COWS

− If >4, stop and wait 1-2 more days

− If less than 4, continue

1) Administer naloxone 0.4 mg (1 cc) i.m. to deltoid and observe

for 20 minutes

2) If no change in COWS administer additional 0.8 mg (2 cc) to

the other deltoid and monitor for additional 20 minutes

Test is positive if increase in COWS 2 or more from pre-injection

score

− If positive challenge, do not administer XR-naltrexone; wait

1-2 days and repeat the challenge

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Challenge Procedures

• P.O. Naltrexone Challenge Procedure

Obtain baseline COWS; if 4 or less proceed with the

challenge

1) Administer naltrexone 25 mg p.o. and observe for 90

minutes

If COWS increase is less than 2, okay to proceed with

injection

In case of positive challenge, treat withdrawal with adjunctive

medications and reschedule injection for next day

Administer XR-naltrexone (no need for repeated challenge

the next day unless there was a new episode of use)

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Jane

• You provide Jane with additional medication to treat her

withdrawal symptoms and see her back in five days

• Denies any opioid use

• Urine toxicology is negative for opioids

• Has mild rhinorrhea and a COWS of 2

• Would like to try the challenge today

• Given naltrexone 25 mg p.o. from your office supplies

• Observed for 90 minutes and her COWS increases to 3

• Given the XR-naltrexone injection and tolerates it without any

difficulty

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Summary

Induction is an important aspect in delivery of

medications to treat opioid use disorders

• There are multiple approaches to induction of

buprenorphine and naltrexone in office settings

Providers and patients can identify strategies that

coincide with their needs/treatment goals

• Precipitated withdrawal is rare, and should be

managed with appropriate medications to facilitate

ongoing engagement in treatment

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References

• Wesson, D. R., & Ling, W. (2003). The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive

Drugs, 35(2), 253–9.

https://www.drugabuse.gov/sites/default/files/files/ClinicalOpiateWithdrawalScale.pdf

• XR-Naltrexone: A Step-by-Step Guide. http://pcssnow.org/wp-

content/uploads/2017/02/Naltrexone_Step-by-Step_Virtual_Brochure-1.pdf.

• Casadonte P. Buprenorphine Induction. https://pcssnow.org/wp-content/uploads/2014/02/PCSS-

MATGuidanceBuprenorphineInduction.Casadonte.pdf.

• Nielsen S, Hillhouse M, Weiss RD, et al. 2014. The relationship between primary opioid and

buprenorphine-naloxone induction outcomes in a prescription opioid dependent sample. Am J Addict.

Jul-Aug;23(4):343-8.

• Sohler, et al. Home- versus office-based buprenorphine inductions for opioid-dependent patients. J

Subst Abuse Treat. 2010 Mar; 38(2): 153-159.

• Unobserved "home" induction onto buprenorphine. Lee JD, Vocci F, Fiellin DA. J Addict Med. 2014

Sep-Oct;8(5):299-308.

• Home Buprenorphine/Naloxone Induction in Primary Care

Joshua D. Lee, MD MSc eta all J Gen Intern Med. 2009 Feb; 24(2): 226–232.

• Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100mg of daily

methadone. Rosado J, Walsh SL, Bigelow GE, Strain EC. Drug Alcohol Depend. 2007 Oct 8;90(2-

3):261-9. Epub 2007 May 22.

• Kleber HD, Kosten TR. 1984. Naltrexone induction: psychologic and pharmacologic strategies. J Clin

Psychiatry 45:29-38

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References

• Kleber HD, Kosten TR. 1984. Naltrexone induction: psychologic and pharmacologic strategies. J Clin

Psychiatry 45:29-38

• Sigmon SC, Bisaga A, Nunes EV, O'Connor PG, Kosten T, Woody G. Opioid Detoxification and Naltrexone

Induction Strategies: Recommendations for Clinical Practice. Am. J. Drug & Alc. Abuse, 2012, 38. 187-99.

• Nielsen S, Hillhouse M, Weiss RD, et al. 2014. The relationship between primary opioid and buprenorphine-

naloxone induction outcomes in a prescription opioid dependent sample. Am J Addict. Jul-Aug;23(4):343-8.

• Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100mg of daily

methadone. Rosado J, Walsh SL, Bigelow GE, Strain EC. Drug Alcohol Depend. 2007 Oct 8;90(2-3):261-9.

Epub 2007 May 22.

• https://www.drugabuse.gov/nidamed-medical-health-professionals/discipline-specific-resources/initiating-

buprenorphine-treatment-in-emergency-department/frequently-asked-questions-about-ed-initiated-

buprenorphine

• Whitley SD et al J Subst Abuse Treat. 2010 Jul;39(1):5 1-7.

• A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus

standard-of-care office-based inductions. Cunningham CO, et al J Subst Abuse Treat. 2011 Jun;40(4):349-

56.

• Unobserved versus observed office buprenorphine/naloxone induction: a pilot randomized clinical trial.

Gunderson EW et al Addict Behav. 2010 May;35(5):537-40.

• National Institute on Drug Abuse. Frequently Asked Questions about ED-Initiated Buprenorphine. NIDA.

https://www.drugabuse.gov/nidamed-medical-health-professionals/discipline-specific-resources/initiating-

buprenorphine-treatment-in-emergency-department/frequently-asked-questions-about-ed-initiated-

buprenorphine. Published September 11, 2018. Accessed July 2019.

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PCSS Mentoring Program

PCSS Mentor Program is designed to offer general

information to clinicians about evidence-based clinical

practices in prescribing medications for opioid addiction.

PCSS Mentors are a national network of providers with

expertise in addictions, pain, evidence-based treatment

including medication-assisted treatment.

• 3-tiered approach allows every mentor/mentee relationship

to be unique and catered to the specific needs of the

mentee.

• No cost. For more information visit:

https://pcssNOW.org/mentoring/

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Abuse Training

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Medicine

PCSS is a collaborative effort led by the American Academy of Addiction

Psychiatry (AAAP) in partnership with:

43

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