8/24/2011

1

Buprenorphine:A Guide for Nurses

Colleen LaBelle, RN, ACRN, CARN

LTJG Sara Azimi-Bolourian, MSN,MHA,MBA

ASPMN September 9th, 2011

Background

The Food and Drug Administration (FDA) approved buprenorphine monotherapy product, Subutex®, and a buprenorphine/naloxone combination product, Suboxone®, for use in office-based settings (October 2002)

Recent studies attribute inadequate staff education and training to the inconsistency between science and practice. Nurses in these settings have reported attending the fewest ongoing clinical trainings in substance abuse (Wechsberg & Kasten, 2007).

Background cont’

Under the Drug Addiction Treatment Act of 2000 (DATA 2000), Advanced Practice Nurses and Nurse Practitioners may not prescribe or dispense buprenorphine products for the treatment of addiction even in States that allow them to prescribe scheduled medications under certain controls, supervisions and other restrictions.

8/24/2011

2

Background Cont’

Nurses working in Opioid Treatment programs (OTPs) have essential roles in the assessment/screening, treatment monitoring and counseling of patients receiving buprenorphine for the treatment of addiction.

Challenges to implementing treatment with a new population of patients addicted to opioids and other drugs, as well as medication diversion and patient confidentiality issues, require nurses to improve their professional skills and prepare them for the implementation of best practices in addiction settings.

Introduction

The project initiated in 2006 to develop a guideline for nurse on use of buprenorphine in addiction treatment settings.

An extensive research was done in the field of nursing and addiction treatment and recent evidence based practice information was incorporated into the publication. The final draft of the guideline was reviewed by two addiction expert nurses, as well as experts from SAMHSA, FDA and NIDA. The Guideline was published on March 25, 2009 and also available online at http://buprenorphine.samhsa.gov

Purpose of This Guide

This guide is intended to provide nurse (Including Registered Nurses (RNs), Licensed Practical Nurses (LPNs), Nurse Practitioners (NPs), and Advanced Practice Nurses (APNs)) with general infromation about buprenorphine products– Suboxone® (buprenorphine and naloxone) and Subutex (buprenorphine)–for the pharmacological treatment of opioid addiction. The guide can also serve as a resource to help working with community physicians to improve treatment outcomes for individuals receiving office-based treatment and primary care settings for opioid addiction.

8/24/2011

3

Learning Objective

The guide is intended to fulfill the following objectives:

To provide nurses with general information on the pharmacology, safety profile, adverse effects, interactions, cautions, contraindications, and abuse potential of buprenorphine products (Suboxone® and Subutex®)

To increase nurses’ factual knowledge on protocols for the use of buprenorphine products in medically-supervised withdrawal (detoxification) and maintenance treatment services

To help nurses, in conjunction with authorized physicians, design strategies for providing comprehensive physical and psycho-social assessments, treatment monitoring and appropriate referral for individuals with opioid addiction and co-occurring medical and psychiatric conditions.

Impact of the guideline

The potential impact of this Guide will be initially on:

Nursing practice of nurses working with individuals who are addicted to opioids in office-based settings (e.g., dispencing responsibility, monitor adverse reactions)

1200 SAMHSA’s certified Opioid Treatment Programs, Primary care settings, HIV clinics, Community health centers. Help nurses apply evidence-based practice during patient’s induction,

stabilization, and maintenance. Enhance patient’s safety by reducing medication errors and overdoses. The

Guide Further promoted to be used as an education supplemental resource in the

Physician Clinical Support System, which provides mentoring to physicians, nurses, and physician assistants working with opioid dependence patients.

Will promote a mutually respectful team environment in which nurses and physicians collaboratively work to improve the care provided to individuals who are addicted to opioids.

Buprenorphine and the Role of the Nurse

The nurse’s roles with patients receiving buprenorphine for the treatment of addiction (1) may be subject to State practice regulations and (2) may include, but not be limited to:

Conducting screening, assessment, treatment monitoring, counseling, and supportive services;

Educating patients, their family members, or other supportive individuals about buprenorphine therapy as well as risks, benefits, potential side effects, interactions, program requirements, consents, and treatment contracts;

8/24/2011

4

Buprenorphine and the Role of the Nurse

Involving patients in the development of the treatment plan, and working with the patient and the interdisciplinary team to individualize the plan for meeting the patients’ needs;

Enhancing treatment readiness, supporting treatment completion, ensuring safety, and promoting sustained recovery outcomes for individuals undergoing buprenorphine treatment for opioid addiction;

Buprenorphine and the Role of the Nurse

Improving access, identifying community resources, and providing information about them; and explaining reimbursement options for office-based buprenorphine treatment;

Assisting patients in accessing care elsewhere when the present practice is not a suitable option for them; and assisting patients in accessing other treatment options as needed (e.g., day treatment, residential, outpatient, methadone detoxification or maintenance, etc.).

Nursing Practice and the Use of Buprenorphine for the Treatment of Opioid

AddictionScreening:

Initial screening (Drug Abuse Screening Test “DSAT-10”)

Ruling out comorbid acute or chronic pain disorders and opioid dependence

Ruling out polysubstnace use-consider using the Readiness Ruler

8/24/2011

5

Screening Cont’

Ruling out co-occurring psychiatric disorders—consider using Mental Health Screening Form III (MHSF-III)

Questioning about potential pregnancy and child-bearing status

Screening for infectious diseases (hepatitis viruses, HIV, tuberculosis (TB), sexually transmitted diseases (STDs))

Screening out domestic violence or abuse

Nursing Practice Cont’

Assessment:

Complete history

Physical examination

Assessing intoxification and overdose (Withdrawal Instrument Score-COWS)

Assesment Cont’

Diagnosis of Opioid related disorders using DSM-IV-TR

Appropriateness for treatment and setting

Medical co-morbidities

Psych co-morbidities

Substance Abuse History, psychiatric disorder history, family history, and medical history

8/24/2011

6

Drug Addiction Treatment Act (DATA) 2000

Amendment to the Controlled Substances Act

Allows physician to prescribe narcotic drugs scheduled III, IV or V, FDA approved for opioid maintenance or detoxification treatmentPrior 10/2002 no drug existed

Methadone does not qualify Schedule II

A New Law

Drug Addiction Treatment Act of 2000 (DATA 2000)

Expands treatment options to include both the general health care system and opioid treatment programs. Expands number of available treatment slots Allows opioid treatment in office settings Sets physician qualifications for prescribing the

medication

Giving opioid agonist treatment medication in OTP

Medication ordered by OTP, under OTP DEA number

Stored in OTP (DEA approved) safe

Dispensed at OTP (not prescribed)

Observed dose required by regulation

No restriction in law on number of patients

8/24/2011

7

DATA 2000: Physician Qualifications

Physicians must: Be licensed to practice by his/her state Have the capacity to refer patients for psychosocial

treatment Limit number of patients receiving buprenorphine

to 30 patients for a least the first year File for a new waiver after first year to increase their

limit to 100 patients. Be qualified to provide buprenorphine and receive a

license waiver

Only physicians can prescribe the medication.

However, the entire treatment system should be

engaged.

DATA 2000: waiver

After notification, (online, fax, or letter) Letter arrives from CSAT

Attorney general assigns a second DEA#

Waiver in effect in 45 days

8/24/2011

8

New DEA number, (green card)

Usually the old number is retained for other scheduled substances

The new number is used only for DATA2000

Usually the new number is exactly the old one, except the first letter is replaced by an X:

Example: AM1234567

XM1234567

FDA Approval and DEA scheduling: 2002

Two sublingual tablets: Suboxone® and Subutex®

Labeled for use in treatment of opiate addiction

All buprenorphine products now schedule III

Conclusion

This guideline provides nurses working in OTPs with information regarding screening and assessment of opioid dependence and its associated problems. It contains detailed protocols for the use of buprenorphine under a variety of clinical scenarios, including the use of buprenorphine with patients who are experiencing co-occurring pain or psychiatric disorders or chemical dependence involving more than one substance.

8/24/2011

9

Who Uses Heroin?

Individuals of all ages use heroin: More than 3.7 million US residents aged

12 and older have used heroin at least once in their lifetime.

Heroin use among high school students is a particular problem. Slightly more than 1 percent of US high school seniors used the drug at least once in their lifetime, and nearly half of those injected the drug.

SOURCE: National Survey on Drug Use and Health, 2008; Monitoring the Future Survey, 2008.

Addiction: the disease

1956: American Medical Association The illness can be described The course of the illness is predictable and

progressive The disease is primary – that is, it is not just a

symptom of some other underlying disorder It is permanent It is terminal: If left untreated, can lead to morbidity

and mortality

Solutions Outpatient Services; Texas Department of State Health Services

Addiction and the limbic system:

The part of the brain hijacked by addiction is in the limbic system, the part responsible for survival.

During withdrawal and craving, the limbic system’s message is ‘urgent need’ for survival.

8/24/2011

10

Repeated Opioid Use

Repeated administration of opioids and activation of the mu receptors results in: Physical Tolerance

Diminishing effect from the same dose or

Need for larger doses to produce the same effect

Physical Dependence If dose is reduced or stopped withdrawal syndrome develops

Note different concept then DSM-IV “Dependence Disorders”

Tolerance and dependence, which are dose related, manifest as an Opioid Withdrawal Syndrome Which develops upon reduction or cessation of opioid use

Criteria for Office-based Treatment

Meet eligibility criteria: Including DSM IV Criteria

Understand treatment; give informed consent No medical or psychiatric contraindications to

treatment Uphold elements of treatment agreement Comply with treatment and monitoring plan Medication safety: dosing and storage

What’s What? Agonists, Partial Agonists,

and AntagonistsAgonist

Partial Agonist

Antagonist

Morphine-like effect (e.g., heroin)

Maximum effect is less than a full agonist (e.g., buprenorphine)

No effect in absence of an opiate or opiate dependence (e.g., naloxone)

8/24/2011

11

Function at ReceptorsFull Agonists

Mureceptor

Full agonist binding …

• activates the mu receptor

• is highly reinforcing

• is the most abused opioid type

• includes heroin, methadone, & others

Full Agonist Activity Levels

Effect

0

10

20

30

40

50

60

70

80

90

100

Full Agonist(e.g. heroin, methadone, etc.)

Increasing dose produces increasing receptor activity

overdose

no drug high dose

DRUG DOSE

low dose

Methadone Maintenance

Evidence-based treatment using the medical model

Includes interdisciplinary care, mandated counseling

Includes behavioral interventions, testing

Includes diversion control plans

8/24/2011

12

Drawbacks to Methadone Daily attendance

Transportation

Strict rules and monitoring

Risk of diversion

Risk of overdose

Risk by association and location…

Difficulty moving on…

Stigma

Methadone and HIV Prevention

Methadone patients report less needle and syringe sharing

Methadone patients are 3-6 times less likely to become HIV positive when compared to out-of-treatment heroin users, including the population that continues to use drugs.

Buprenorphine maintenance is hoped to have a similar impact

Drucker, 1998

Medication Maintenance Goals

Alleviate physical withdrawal

“Narcotic blockade”

Alleviate drug craving

Normalized deranged brain changes

Normalized deranged physiology

8/24/2011

13

Function at ReceptorsPartial Agonists

Mureceptor

• activates the receptor at lower levels

• is relatively less reinforcing

• is a less abused opioid type

• includes buprenorphine

Partial agonist binding …

Partial Agonist Activity Levels

no drug high dose

DRUG DOSE

low dose

EFFECT

0

10

20

30

40

50

60

70

80

90

100

Full Agonist (e.g. heroin)

Partial Agonist (e.g. buprenorphine)

At therapeutic levels, act similar to full agonists

But due to its “ceiling” maximum opioid agonist effect is never achieved

Function at Receptors: Antagonists

Mureceptor

• occupies without activating

• is not reinforcing

• blocks abused agonist opioid types

• includes naloxone and naltrexone

Antagonist binding …

8/24/2011

14

Naltrexone

Pure opioid antagonist with good oral absorption

Duration of action 24-48 hours

1984: FDA approved to treat opioid dependence

Well tolerated and safe

Naltrexone

Low interest among “street addicts”

No better than placebo except in highly motivated patients

Impaired physicians > 80% abstinence at 18 months

BUPRENORPHINE

8/24/2011

15

Function at ReceptorsPartial Agonists

Mureceptor

• activates the receptor at lower levels

• is relatively less reinforcing

• is a less abused opioid type

• includes buprenorphine

Partial agonist binding …

Partial Agonist Activity Levels

no drug high dose

DRUG DOSE

low dose

EFFECT

0

10

20

30

40

50

60

70

80

90

100

Full Agonist (e.g. heroin)

Partial Agonist (e.g. buprenorphine)

At therapeutic levels, act similar to full agonists

But due to its “ceiling” maximum opioid agonist effect is never achieved

Goals of Pharmacotherapy with Buprenorphine:

Prevention or reduction of withdrawal symptoms

Prevention or reduction of drug craving Prevention of relapse to use of addictive drug Restoration to or toward normalcy of any

physiological function disrupted by drug abuse

8/24/2011

16

MuReceptor

Full Agonist Bound to ReceptorBup affinity is higher

Therefore Full Agonist is displaced

Receptor Affinity

• AFFINITY is the strength with which a drug physically binds to a receptor Buprenorphine’s affinity is very strong and it will displace full

agonists like heroin and methadone

Receptor DissociationSpeed (slow or fast) of disengagement or

uncoupling of a drug from the receptor• Buprenorphine’s dissociation is slow

• Therefore buprenorphine blocks heroin from binding

MuReceptor

Bup dissociation is slow

Therefore Full Agonists can’t bind

Borrowed from Tom Pichot, MD

Precipitating Withdrawal

Buprenorphine will precipitate withdrawal when it displaces full agonist off the mu receptors

0

10

20

30

40

50

60

7080

90

100

% Mu Receptor

IntrinsicActivity

Full Agonist (e.g. heroin)

Partial Agonist (e.g. buprenorphine)

no drug high doseDRUG DOSE

low dose

A Net Decrease in Receptor Activity if a Partial Agonist displaces Full Agonist

8/24/2011

17

Rapid onset of effect

Readily absorbed sublingually: 5-20 min. for tablet to dissolve

Rapid onset of action: 30-60 min

Peak plasma levels at 1-2 h

Peak subjective/physiologic effect at 1-4 h

How Does Buprenorphine Work?

“Ceiling effect” on opioid effects

High affinity for opioid receptor

Slow dissociation from opioid receptor

Formulated with naloxone Naloxone blocks opiate effect if injected

Naloxone is degraded (inert) if taking orally

“Combo Tablet”Buprenophine/Naloxone

Decreases abuse potential by injection route

Sublingual use = Buprenorphine effect

Buprenorphine has very good bioavailability andnaloxone has very low bioavailability

Parenteral use = Naloxone effect

Acute opioid withdrawal in physically dependentpatients

8/24/2011

18

Buprenorphine is generallywell tolerated but…

Common side effects may include: Headache Constipation Nausea Anxiety Sweating Insomnia Pain

Less Common Side Effects:

Elevated Liver enzymes

Liver toxicity

Vomiting

Drug/drug interactions

CNS Depression

Allergic reaction: rash, hives, bronchospasm

HepatitisCase reports (4)

Transaminase increased, 30-50 times normal, with intravenous buprenorphine in patients infected with hepatitis C

Case Report (1) HIV and Hepatitis C positive became jaundiced, liver necrosis with sublingual buprenorphine

Intravenous users recovered after stopped injecting, two did not stop sublingual

Buprenorphine treatment and HCV

8/24/2011

19

Buprenorphine treatment and HCV

Case Reports (7) patients 1 patients was injecting buprenorphine

Other 6 took as prescribed sublingual

Average ALT 39 times normal

All had serologic evidence of HCV

Buprenorphine continued in all with 3 having dose reduction of 50%

All 7 patients recovered

Interactions, Cautions, and Contraindications:

Package insert Suboxone/Subutex: http://www.suboxone.com/pdfs/suboxonePI.pdf

Complete list of substrates, inhibitors & inducers

www.drug-interactions.com

Bioavailability

Poor oral bioavailability Sublingual administration is the primary route of

administration

High lipid solubility Expected to be active by the intranasal route

8/24/2011

20

Breaking down buprenorphine

Hepatic metabolism: CYP450 3A4 N-dealkylation to norbuprenorphine Glucuronidation

Excretion 30% urine: can test for buprenorphine in urine 70% feces

Pharmacodynamic drug interactions

CNS depressants and sedatives (eg, benzodiazepines): All opioids have additive sedative effects when used in

combination with other sedatives Increased potential for respiratory depression, heavy sedation, coma,

and death

Despite favorable safety, use caution with concomitant psychotropics (eg., benzodiazepines)

Alcohol and Suboxone

Deaths in France associated with central nervous system depressants including alcohol (Reynaud et al. 1998a, Gaulier et al. 2000)

Assess alcohol history: Address prior to OBOT; Detox, abstinence

Monitor during treatment; breathalyzer, serum

8/24/2011

21

Overdose Risk

Overdose risk low High doses should not produce significant CNS or

respiratory depression

Risk higher with combined abuse of other sedatives e.g. benzodiazepine

Deaths reported from France Mono tablets dissolved and injected with concurrent high

potency benzodiazepine use

Relative NOT absolute contraindication for concurrent use with other sedatives

Getting Started…

History

Substance

Prior treatments

Medical

Psychiatric

Family

8/24/2011

22

Nursing Assessment:

Intake

Consents/Contracts

Education

Urine toxicology screen

LFT’s, Hepatitis serologies, RPR, CBC, pregnancy test

Goal of Medical Assessment:

Establish the diagnosis Determine appropriateness for treatment Make initial treatment recommendations Formulate initial treatment plan Plan for engagement in psychological treatment Ensure no contraindications to treatment Assess other medical problems Assess other psychosocial problems

CSAT 2004

Patient Agreement

Sets the stage for ongoing relationship

Clear message about rules

Patient involvement

Behavior is part of treatment

8/24/2011

23

How to Deal with Patients Day to Day

Clinic guidelines Be consistent Book appointments that coincide with refills Inform patients refill will only occur at that

time/group/ etc… Consent and contract spell out agreement…..Be

Consistent

Rules & Expectations for the Patient

Treatment philosophy: what is expected

Medication dispensing procedures: when, how, who

Medication issues: side effects, symptoms

Behavioral component to therapy

Proper adherence to induction and maintenance protocols

Rules & Expectations for the Patient

Dosing guidelines

Urine testing procedures

Illicit drug or alcohol use

Selling or trading medication

Personal treatment protocol

Aggressive statements/acts

Theft/destruction of property

8/24/2011

24

Rules & Expectations for the Patient

Do both in writing and verbally Give the patient a copy Have patient sign and date a copy, and

keep in the patient’s chart Review periodically (as needed) with

patients Review (and revise as needed) All staff should be aware of the

requirements

Induction

Planning for Induction:

Build a Relationship, Trust, support…. Early stages of withdrawal prior to

induction

Review with patient ahead of time usage history, withdrawal, last use. Short acting, long acting opioids: What did

they last use?

8/24/2011

25

Long Acting Opioids:

24 hours for Oxycontin P.O.

48+ hours for Methadone

Much harder and longer process

Patient and provider need to be

Committed

Timing of induction: long-acting opioids

Abstain for at least 48+ hours

Assess for withdrawal

Timing is often not a good indicator Need to assess symptoms

Slow and Steady

Buprenorphine induction: Long Acting Opioid….. Methadone

Methadone in tissue stores are a factor.

Decrease the daily dose until stable: ≤30 mg of methadone.

Begin induction at least 48-96 hours after last dose of methadone. Give no further methadone once buprenorphine induction is started.

Requires time, patience, and support.

8/24/2011

26

Short Acting Opioids:

8 to 12 hours

Oxycodone (Percocet®, crushed

Oxycontin®)

Hydrocodone (Vicodin®)

Heroin

Morphine

Timing of induction: short-acting opioids

Abstain 8-12 hours (mild withdrawal)

If patient is not in documented withdrawalreview history.

Assess, support and wait

What did they use in the last 24hours, ask the questions…… Methadone, oxycontin, heroin…..

Patient instructions during first dose:

Put tablet(s) under tongue: sublingual

Don’t talk, don’t swallow: saliva pools

May use mirror, watch the tablet(s)

gradually shrink as they dissolve.

May drink fluids before not during

8/24/2011

27

Administration Techniques:

Crush the tablet: pour under the tongue (not listed as route of administration) Shorter duration of absorption

Decreased diversion

Easier to observe for: providers, parents, program staff

First dose of sublingual buprenorphine

Patient in clinical opiate withdrawal

Objective signs are key to making dx (can be challenging)

COWS > 8-12

Start with 2-4mg sl

Assess 40min-1 hour after dosing

Better, worse, or the same

Induction:

Continue to titrate until symptoms resolve

Reassess patient 40minutes to 1 hour after first dose

Dose with 2mg sl

Reassess over the next few hours

Stabilize day one around 8mg or per your protocol

8/24/2011

28

Typical Target doses:

First day: up to 8mg

Second day: up to 16 mg

Final dose usually 8-16 mg

Receptor 95% occupied at 16mg

Very few patients need up to 32mg (max)

Target dose 8-16mg

Assessment, support, ongoing education

Adjust dose accordingly based on patient’s experiences on first day (i.e., higher dose if there were withdrawal symptoms; lower dose if patient was over-medicated at end of first day)

Goal: Eliminate withdrawal, and craving

Finding the correct dose:

On second day, have patient return to the office for assessment, second day dosing

Adjust dose accordingly based on patient’s experiences on first day (i.e., higher dose if there were withdrawal symptoms after leaving your office; lower dose if patient was over-medicated at end of first day)

Buprenorphine Induction

8/24/2011

29

Patients not physically dependent on opioidsFor example, patient at high risk for relapse to opioid

use, but just out of prison.

First dose: 2 mg sublingual buprenorphine

Monitor in office for 2+ hours after first dose

Gradually increase dose over days

Buprenorphine Induction procedure

Comfort Measures:

Ibuprofen: muscle aches

Tylenol: pain, headache

Maalox: GI distress

Imodium: Diarrhea

Compazine: Nausea, Vomiting

Bentyl: abdominal cramps

Benedryl, Trazadone, Tylenol PM: Sleep

Clonidine: Severe anxiety

Comfort Measures:

Taste perversion: strips, soda before, crush

Headaches: Take before bed

Nausea: Take at bedtime or with meals

Sweating: Divide dose

Insomnia: Take at night

Dose splitting: patient preference, behavior, better tolerated

8/24/2011

30

Follow up:

Assess dose, frequency, cravings, withdrawal

Ongoing education: dosing, side effects, interactions, support.

Counseling, self help check in

Psychiatric evaluation and follow up as needed

Medical issues: vaccines, follow up, treatment HIV, HCV…Engage in care

Pregnancy

Social supports: housing, job, family, friends

Monitoring

Monitoring: Urine Screening

Why conduct urine drug testing?

• Drug abuse a chronic disorder – relapse can occur

• Patients may deny or minimize use

• Urine testing an integral part of on-going evaluation and treatment planning

8/24/2011

31

Characteristics of Abuse Potential

Route of administration Faster route has a greater abuse potential

Injecting IV Injecting SQ Oral

Drug Half life Briefer half-life has a greater abuse potential

Heroin Methadone

Lipophilicity (faster across blood brain barrier) Higher liophilicity has a greater abuse potential

Heroin Morphine Methadone

Recognize Patient Requests or Behaviors That May Indicate Diversion

Diversion

Asking for higher dose than needed

Asking for early refills

Asking specifically for a

buprenorphine-only product

Stealing prescription

pads

Proper Storage and Handling

Avoid pediatric exposure Store the medication “out of the sight and reach of children” Keep the medication in the container it came in

prescription vial with child resistant closureNever leave tablets out of the container – even for a few minutes Patients should obtain an extra prescription vial that is labeled properly if

medication is to be stored in multiple locations Never share pills, even with the best of intentions

Sharing pills is diversion The patient cannot guarantee the behavior of someone else with respect to

the safe handling and storage of the medication Provide the Poison Control Center phone number

1-800-222-1222

8/24/2011

32

Referral and Discontinuation

Higher level of care needed: MMTP, Residential, detox, IOP

Immediate dismissal for behavior

Taper for administrative non-compliance

Special populations and buprenorphine

HIV (fewer clinically noted medication interactions with HAART)

Cardiac (QT prolongation not an issue) Logistics (take homes easier in case of long

distances from clinic)

Addiction Alters Pain Experience

Both stimulant and opioid abusers have less pain tolerance than peers in remission or matched controls

Former opioid abusers have decreased pain tolerance to pain compared with non-addict siblings

HIV-infected patients w/ hx of substance abuse required higher doses of opioid analgesics than patients without a hx of substance abuse

Martin J (1965), Ho and Dole V (1979), Compton P (1994, 2001), Swica Y (2002)

8/24/2011

33

Opioid Agonist Treatment and Pain

The “Opioid Debt”

Patients who are physically dependent on opioids (ie. methadone, buprenorphine) must be maintained on daily equivalence before ANY analgesic effect is realized with opioids used for acute pain management

Doug Gourlay, MD College of Physicians and Surgeons of Ontario

Buprenorphine as an Analgesic

In U.S., sublingual formulation not developed for analgesic purposes

Small studies in Europe and Asia demonstrate analgesic efficacy of sublingual formulation (0.2-0.8 mg q 6-8 h) in post-operative pain Ceiling analgesic dose ~ 1.5-5 mg

Onset of analgesia ~ 30 minutes

Peak analgesia ~ 3 hours

Duration of analgesia ~6-8 hours

Acute Pain Management:

Continue buprenorphine maintenance, titrate short acting opioid

Likely to require higher doses due to competition at receptor

Increased sensitivity to full agonist: CNS depression may occur

8/24/2011

34

Acute Pain Management Approaches:

Divide buprenorphine every 6-8 hours

No ceiling analgesic effect

Ceiling effect for respiratory depression May safely administer higher doses

One case report 72mg acute pain Book et al. 2007

Acute Pain Management Approaches:

Discontinue the buprenorphine Treat with as full opioid agonist

Titrate to effect: withdrawal/analgesia

Resolution of pain Discontinue full agonist

Restart buprenorphine after induction

Buprenorphine Maintenance: Acute Pain

Mild - moderate pain (e.g., dental extraction)1) Continue buprenorphine maintenance

2) Use short-acting opioid analgesics

Moderate - severe pain (e.g., renal stone)1) Discontinue buprenorphine

2) Treat with opioid analgesics until pain resolves

3) Re-induction with buprenorphine using established protocols

Alford DP, Compton P, Samet JH. Annals of Internal Medicine 2006

8/24/2011

35

Buprenorphine MaintenanceAcute Pain: Inpatient

Moderate - severe pain (e.g., elective surgery, trauma)

1) Discontinue buprenorphine

2) Methadone ~ 30-40 mg po qd for opioid maintenance

3) Opioid analgesics until pain resolves

4) Discontinue methadone and re-induction with buprenorphine using established protocols

Alford DP, Compton P, Samet JH. Annals of Internal Medicine 2006

Chronic Pain ManagementBuprenorphine Maintenance

Try non-pharmacologic and nonopioid therapies

If pain persists and opioid analgesics are required…

Because buprenorphine may cause precipitated withdrawal with concurrent long-acting opioid analgesics…

Buprenorphine-maintenance should be discontinued and patient’s opioid dependence treated in a methadone maintenance treatment program

Pregnancy

8/24/2011

36

Pregnancy Currently buprenorphine is a Category C

medication. This means it is not approved for use during pregnancy.

Studies conducted to date suggest that buprenorphine may be an excellent option for pregnant women.

Randomized trials are underway to determine the safety and effectiveness of using buprenorphine during pregnancy.

Patient Selection: Issues Involving Consultation with the Physician

Buprenorphine and Pregnancy

Neonatal abstinent syndrome (NAS)

-Within 12 to 48 hours, peaks 72 to 96, lasts 120-168 hours (some seen 6 to 10 weeks)

Found to be less intense than methadone (Johnson et al. 2003)

Buprenorphine and Pregnancy

Buprenorphine (Category C) use in pregnancy.

Should not use combo tablet, Suboxone®

(buprenorphine/naloxone), during pregnancy.

Switch to mono tablet Subutex®

Pregnant women treated with buprenorphine have had good withdrawal suppression with once daily dosing

Minimal information regarding need for dose adjustments during pregnancy e.g. third trimester

8/24/2011

37

Managing Pregnancy on Buprenorphine

Mono tablet

Smaller prescriptions (limit diversion)

Frequent Visits

Urine toxicology screens (buprenorphine)

Counseling, support

High Risk OB Setting

Patients’ Main Concerns

“DCF” / Department of Family and Children

Neonatal Abstinence Syndrome

Disclosure

HCV

Parenting/ Housing

Treatment duration (days)

Rem

aini

ng in

tre

atm

ent

(nr

)

0

5

10

15

20

0 50 100 150 200 250 300 350

Control

Buprenorphine

Buprenorphine Efficacy

Kakko J et al. Lancet 2003

75% Retention

75% UTS negative in treatment

20% mortality in the placebo group

N=20

N=20

8/24/2011

38

Thank You for your attention..

Colleen.labelle@bmc.org

Sara.Azimi-Bolourian@SAMHSA.hhs.gov

Thank You

“If we do nothing people will die” Dr Wesley Clark Director Center for Substance

Abuse Treatment and Mental Health Services Administration, U.S. Department of Health and Human Services

Websites on Buprenorphine

www.buprenorphine.samhsa.org

www.asam.org

Email or phone support: Colleen.Labelle@bmc.org

617-414-7453