Extended-Release and LongActing Opioid Analgesics Risk
Evaluation and Mitigation
Strategy (REMS)
Central Appalachia Inter-professional
Pain Education Collaborative (CAIPEC)
Faculty Information
Bios:
Roberto Cardarelli, DO, MPH, FAAFP is Professor and Chief of
Community Medicine at the University of Kentucky College of
Medicine and is an active researcher in practice transformation
and health services research. He serves as the Director of the
Kentucky Ambulatory Network (KAN) with a history of research
funding from NIH, Pfizer Medical Education, Meadows Foundation,
American Academy of Family Physicians, Passport Health, and UK’s
Center for Clinical and Translational Science.
William Elder, PhD is a Professor and Director of Behavioral Science
in the Department of Family and Community Medicine in
Lexington, KY. As a clinical psychologist he sees patients with a full
range of mental disorders. He leads or co led research and
educational projects funded by HRSA, NIH, Pfizer Medical
Education and others and he has served on multiple regional and
national advisory panels for education and research.
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Content Development/Planner/Reviewer Disclosures
The following individuals disclose one or more relevant financial relationships:
Roberto Cardarelli,
DO, MPH
Professor of Family % Community Medicine,
University of Kentucky, Lexington, KY
William Elder, PhD
Professor of Family % Community Medicine,
University of Kentucky, Lexington, KY
Grant/research support consultant: Passport Health, UK CCTS,
NIH, Pfizer, CDC, CMS, American Board of Family Medicine.
Grant/research support consultant: HRSA, Pfizer, NIH
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3 | © CO*RE 2014
Central Appalachia Inter-professional Pain
Education Collaborative (CAIPEC)
Funded by an unrestricted grant from Pfizer Medical Education to
develop and deliver a multi-faceted education program on chronic
pain management to provider and healthcare teams in Central
Appalachia. Future FREE events will include:
• Webcasts
• Community Roundtables
• A clinic toolkit to help redesign how chronic pain management is
delivered
• Information on how to do QI projects and receiving Maintenance
of Certification (MOC) credit
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Thank you for your participation today!
Please take the pretest now –
The pretest is part of the
stapled paper handout you
received
Learning Objectives
• Appropriately assess patients for the treatment of pain with ER/LA opioid analgesics,
including analyzing risks versus potential benefits
• Assess patient’s risk of abuse, including substance use and psychiatric history
•
Identify state and federal regulations on opioid prescribing
•
Incorporate strategies to effectively initiate therapy, modify dosing or discontinue use of ER/LA opioid analgesics in
patients with pain
•
Manage ongoing therapy with ER/LA opioid analgesics
•
Incorporate effective counseling for patients and caregivers about the safe use of ER/LA opioid analgesics
•
Discuss general and product-specific drug information related to ER/LA opioid analgesics
CAIPEC will also integrate the following Learning Objectives:
• The Epidemiology of Chronic Pain
• The Biopsychosocial Aspects of Chronic Pain
• Chronic Pain History and Shared Decision Making
• Examination and Diagnostic Testing in Patients with Chronic Pain
• Non-Pharmacologic and Pharmacologic Treatment Options
• Practice Enhancement in Managing People with Chronic Pain through a Teambased Approach
Assessing Patients for
Treatment with ER/LA
Opioid Analgesic Therapy
Module 1
Epidemiology
Prevalence of chronic pain
Not known
Prevalence of significant
$116 million
pain, 2014
Financial cost of pain, 2014 $556 billion
2013 Behavioral Risk Factor Surveillance System
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Epidemiology
% Reporting Disability
National Average
19.6
Kentucky
25.8
West Virginia
27.6
2013 Behavioral Risk Factor Surveillance System
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Overdose Death, and Opioid Prescribing Rates
State
Age Adjusted Drug Overdose death Kilograms of prescription painkillers
rate per 100,000 people (2008)
sold, rates per 10,000 people (2010)
Kentucky
17.9
West Virginia 25.8
9
9.4
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West Virginia
• As the highest overdose rate nationally, WV’s rate is eight times higher than the lowest rate in
North Dakota.
• As of 2013, West Virginia’s number of drug overdose deaths - nearly 29 for every 100,000
residents – even surpassing those killed in auto accidents.
• The number of overdose deaths in WV increased “6 fold” from 1999 to 2010 (mostly from
prescriptions pills).
• For more information about your state there are great resources available at the following site:
http://www.rwjf.org/en/library/articles-and-news/2013/09/interactive--prescription-drugabuse.html
Eyre, E., 2013. Report finds WV leads Nation in Drug Overdose Deaths, Journal of Emergency Medical Services, Retrieved from URL:
http://www.jems.com/articles/2013/09/report-finds-west-virginia-leads-nation.html
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Widespread Abuse and Misuse of Opioids
In 2008, there were 14,800 prescription painkiller deaths
http://www.cdc.gov/homeandrecreationalsafety/rxbrief/. Accessed Jan 2014.
Drug Overdose Deaths by Major Drug Type,
United States, 1999–2010
Opioids
Heroin
Cocaine
Benzodiazepines
18,000
16,000
Number of Deaths
14,000
12,000
10,000
8,000
6,000
4,000
2,000
0
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Year
CDC, National Center for Health Statistics, National Vital Statistics System, CDC Wonder. Updated with 2010
mortality data.
2010
Critical Vocabulary
• Aberrant drug-related behavior: Conduct outside the boundaries of the agreed
upon treatment plan
• Abuse: Any use of an illegal drug, or a medication for a nonmedical purpose
• Addiction: Impaired control over drug use, compulsive use, continued use
despite harm, and/or craving
• Diversion: The intentional transfer of a controlled substance from legitimate
distribution and dispensing channels
• Misuse: Use of a medication other than as directed or as indicated
• Physical dependence: A state of biologic adaptation manifested by a withdrawal
syndrome produced by decreasing blood levels of the drug
• Tolerance: A state of physiologic adaptation in which exposure to a drug induces
a diminution of one or more opioid effects over time
Chou R, et al. J Pain. 2009;10(2):113-130.
REMS Education
Updated
August 2014
On July 9, 2012, the FDA approved a
Risk Evaluation and Mitigation Strategy (REMS)
for extended-release (ER) and long-acting (LA)
opioid medications
Updated August, 2014
http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm. Accessed Jan 2014.
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.
pdf. Accessed October 2014
What Drugs Are Covered by This REMS?
Brand Name Products
Generics
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Avinza® morphine sulfate ER capsules
Butrans® buprenorphine transdermal system
Dolophine® methadone hydrochloride tablets
Duragesic® fentanyl transdermal system
Embeda® morphine sulfate/naltrexone ER
capsules*
Exalgo® hydromorphone hydrochloride ER
tablets
Kadian® morphine sulfate ER capsules
MethadoseTM methadone hydrochloride tablets
MS Contin® morphine sulfate CR tablets
Nucynta® ER tapentadol ER tablets
Opana® ER oxymorphone hydrochloride ER
tablets
OxyContin® oxycodone hydrochloride CR tablets
Palladone® hydromorphone hydrochloride ER
capsules†
ZohydroTM ER hydrocodone bitartrate ER
capsules
Targiniq® ER oxycodone HCl and naloxone HCl
ER tablets
Updated
August 2014
Fentanyl ER transdermal systems
Methadone hydrochloride tablets
Methadone hydrochloride oral concentrate
Methadone hydrochloride oral solution
Morphine sulfate ER tablets
Morphine sulfate ER capsules
Oxycodone hydrochloride ER tablets
*Not currently available due to voluntary recall
(still approved)
†No longer marketed (still approved)
ER/LA Opioid Analgesics REMS. http://www.er-la-opioidrems.com/IwgUI/rems/products.action. Accessed Dec 2013.
Risks of ER/LA Opioid Analgesics
Updated
August 2014
• Overdose with ER/LA formulations
• Abuse by patient or household contacts
– Especially adolescent children
• Inadvertent exposure by household contacts
• Misuse and addiction
• Physical dependence and tolerance
• Interactions with other medications and substances
– Medication reconciliation
• Neonatal opioid withdrawal syndrome with
prolonged use during pregnancy
• Financial (diverting drugs for illegal sale)
Your Patient Complains of Pain:
Where to Start
• Consider source or etiology of pain
• In most circumstances, use a non-opioid pain
medication first
FSMB Model Policy. http://www.fsmb.org/grpol_policydocs.html#2013. Accessed Dec 2013.
4a
Describing Pain
Acute
Sudden onset, usually
identifiable cause
Last less than 1 month
Chronic (our focus!)
3 months or greater, usually
due to a chronic
disease/condition; may have no
obvious cause
Prolonged physical,
psychological impairments
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Biopsychosociology of Chronic Pain
Pathology Process
Normal pain  abnormal pain
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Most people think of pain like Descartes
Much more complex:
Four physiological elements
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Element 1
Transduction
Very complex:
Nociceptors (afferent
nerve endings)
translate noxious
stimuli into nociceptive
impulses
• 30 different nociceptor
types
• Silent nociceptors
transmit only if
inflammation present
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Element 2
Transmission
Afferent nerve signals
travel to dorsal root.
Then project to
thalamus, then to
somatosensory cortexsensory aspects
And frontal cortex and
limbic systememotional responses
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Element 3: Modulation
Process of dampening or amplifying pain related neural
signals
Primarily in dorsal horn
Rich arrays of mu, kappa and delta opioid receptors
5HT and NE neurons
Gate Control
Endogenous ability of brain to increase or decrease
pain transmission in the dorsal horn
Element 4 Perception
Subjective experience of pain
Results from interaction of first three elements and
psychology of individuals
Brain determines if gate is open or closed
Importance of psychological variables
Gate can be controlled by pharmacological and
psychological interventions
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Abnormal Pain
• Not nociceptive pain
• Pain that occurs in the context of nociceptive system that has been altered by
tissue damage or other processes
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Abnormal Pain
• Inflammatory pain
• Acute injury causes tissue inflammation
• Release of bradykinins and serotonin results in sensitization of peripheral
neuroreceptors. Lower firing threshold
• Silent receptors are recruited
• If on-going inflammation (RA or CA) pain will persist
• Inflammation may leave permanent alterations (OA)
Central Sensitization
Excessive or persistent nociceptive signals cause
long term changes
…
•
•
• Wind up-amplification occurring when sufficient signal frequency alter C-Fibers
• Nerve signals get trained to deliver pain signals better
• Allodynia- abnormal response to light touch
• Hypoalgesia
• Primary: at the site of injury: thermal or mechanical
• Secondary: central
• Neuropathic pain
• e.g., Nerves cut off from periphery, such as amputation became hyperactive
• Dorsal horn changes altering sensory input: reorganization, enlargement of receptive fields, altered opioid
sensitivity, enlarged sympathetic nerve terminals and abnormal temporal summation
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Somatic/Visceral Reflexes and Pain
Somatic (ex. Muscles) afferent input
can effect visceral organs and vice
versa
• Left arm pain during a heart attack
• Right shoulder blade pain due to gallstones
Be aware of these potential reflexes
which may impact your workup and
treatment plan
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2c
“Learned” Pain
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Take home points
Understanding these
processes, their
interactions and their
alterations
Appreciation of the multiple
factors that influence pain
Understanding how multiple
types of interventions
including cognitive
behavioral therapies,
mindfulness interventions,
massage and PT may
improve pain
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Clinical Interview: Getting Started
• Complete history
– Family history of substance abuse (does not preclude
treatment with ER/LA opioid)
– Family history of psychiatric disorders
– Social history, including criminal record
• Complete physical examination
• Use a screening tool
– ORT, SOAPP, DIRE
Chou R, et al. J Pain. 2009;10(2):113-130.
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm. Accessed Jan 2014.
Clinical Interview:
Description and Impact of Pain
Description of current pain complaint
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Location
Intensity
Quality
Onset/Duration
Patterns
What causes or increases pain?
Effects of pain on physical, emotional, and psychosocial function
Patient’s pain and functional goals
Heapy A, et al. Psychological and Behavioral Assessment. In: Raj's Practical Management of Pain. 4th ed. 2008;279-295.
Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010.
Clinical Interview: Pain Coping Strategies
Pain Medications
Past use
Current use
•
•
•
Query state PDMP where available to confirm patient report
Contact past providers and obtain prior medical records
Conduct Urine Drug Test (UDT)
Dosage
•
For opioid currently prescribed: opioid, dose, regimen, and
duration
– Important to determine if patient is opioid tolerant
General Effectiveness
Nonpharmacologic strategies and effectiveness
Heapy A, Kerns RD. Psychological and Behavioral Assessment. In: Raj's Practical Management of Pain. 4th ed. 2008;
279-295. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management
of Opioid Therapy for Chronic Pain. 2010.
Risk Factors for Aberrant Drug-related
Behaviors
Family Hx
Substance
Abuse
Personal Hx
Substance
Abuse
Abuse
Misuse
Psychiatric
Disorders
Edlund MJ, et al. Pain. 2007;129(3):355-362.
Chou R, et al. J Pain. 2009;10(2):113-130.
Fishbain DA, et al. Pain Med. 2012;13(9):1212-1226.
Younger
Age
Other Factors:
• History of sexual abuse
• Criminal record
• Low reliability
• Lack of social support
• Smoking
5c
Diagnostic Testing
Dictated based on the H&P
• Not needed (in most) cases- FP and FN consequences (procedures,
further testing)
• Red flag? (Foot drop, fecal incontinence, etc.)
• Failed therapy, surgery is being considered
• Rule in/out concerns- malignancy, fractures because of trauma
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What Were They Thinking?
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Is this patient really in pain?
Is he/she seeking opioids?
Is he/she an abuser?
Is he/she addicted?
• Is the doctor taking my pain
seriously?
• Should I reveal my history?
• Should I reveal my home life?
Clinical Psychological Perspective
Chronic pain should always be considered a mental disorder. First and
foremost
Somatoform Disorder
Correct Diagnosis Somatic Symptom Disorder
• Preoccupation with pain or abnormal
reaction to pain
• Examination out of proportion to disease or
injury
• Significant distress or dysfunction
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Key Psychological Factors
• Temperament; Neurotic; Stoic
• Coping style- active vs passive
• Dysfunctional Coping,
• History of trauma
• Neurosurgical Outcomes Study
• Pending settlements
• Anxiety
• Fearfulness including re-injury
• Associated bracing
• Cognitive Style
• Catastrophic thinking
• California Work Injury Studies
• Depression +/• Cultural and social norms
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Social Side of Chronic Pain
Assess social and family support
Assess impact on work functioning
Family members can:
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Provide assistance too much attention-secondary gain
Be punishing when pain is expressed
Families may need assistance in learning how to change their roles
Provide simple intervention: E.g.. Encourage patient to distract from pain
Work can:
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The ratio of blue collar to white collar in terms of chronic pain related disability is at least 10 to 1. This is because of the
nature of the work,
Injuries affect job abilities, impacting self-esteem and identity
Companies vary in how they will accommodate the injured employee -some punishing and some making job changes. Very
few are willing to stick with someone with long standing injuries
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Psychosocial Evaluation
Manage or refer when:
• SI with or without plan
• Lack of energy
• Differentiated anxiety disorders: PTSD, Panic
Disorder, OCD
• Anhedonia
• Unable to adjust to condition
• Loss of appetite
• Family dysfunction
• Anger outbursts
• Sleep issues; apnea insomnia
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Psychosocial Evaluation-Summary
Questions to assess psychosocial aspects of pain
Global
How is the pain affecting your
life?
Emotional reactions
What’s your mood generally like?
Suicidal thoughts
Do feel like giving up or hurting
yourself?
Cognitions, beliefs, coping with
pain
How do you cope with pain?
Behavioral reactions
What do you do if your pain flares
up?
Family functioning
How do your family or others
respond when you have pain?
Social and occupational
functioning
How are work and social activities
going? How are they impacted by
your pain?
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Set Functional Goals
Functional Status:
• What’s a typical day like?
• What’s the most active thing you do?
• Do you ever stay in bed all day?
• Do you get any exercise?
• How have these things changed over the past weeks/months/years?
• What would you (realistically) like to be able to do?
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Musculoskeletal Examination
Do an overall assessment (i.e., neck, upper/lower extremities, trunk) and a
focused palpitation exam at site of pain
Note if deep or superficial pain
Pay attention to patient’s response during exam
Range of motion, assess functional restrictions
Note the degree that exam can be performed before pain is elicited
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Neurological Examination
Tailor exam based on pain complaint
Assess motor and sensory systems
• Sensory- light touch, pressure, thermal/ mechanical stimuli- allodynia (shouldn’t
cause pain)
• Hyperalgesia- severe pain from stimuli (ex. Pin-prick) that would be expected
• Motor-weakness, ataxia, reduced endurance
• Reflexes should be assessed
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Risk Management for Substance Dependency
• All Biopsychosocial factors
increase risk
• Mental disorders (ADD, OCD,
Bipolar disorder, schizophrenia)
• Substance abuse in family or
personally
• Family link more significant
factor in males
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Validated Questionnaires
ORT
Opioid Risk Tool
SOAPP
Screener & Opioid Assessment for Patients with Pain
DIRE
Diagnosis, Intractability, Risk, and Efficacy inventory
STAR
Screening Tool for Addiction Risk
SISAP
Screening Instrument for Substance Abuse Potential
PDUQ
Prescription Drug Use Questionnaire
• No “gold standard”
• Lack of rigorous testing
Moore TM, et al. Pain Medicine. 2009;10(8):1426-1433.
Opioid Risk Tool (ORT)
Mark each box that applies
1.
2.
Female
Male
Alcohol
1
3
Illegal drugs
2
3
Prescription drugs
4
4
Family Hx of substance abuse
Administer
On initial visit
Prior to opioid therapy
Personal Hx of substance abuse
Alcohol
3
3
Illegal drugs
4
4
Prescription drugs
5
5
Scoring (risk)
3.
Age between 16 & 45 yrs
1
1
0-3: low
4.
Hx of preadolescent sexual abuse
3
0
5.
Psychologic disease
ADD, OCD, bipolar, schizophrenia
2
2
Depression
1
1
Scoring Totals:
http://www.opioidrisk.com/node/2424. Accessed Jan 2014.
Webster LR, et al. Pain Med. 2005;6:432-442.
4-7: moderate
≥ 8: high
Concepts Comprising Medication Risk and
Adherence Measures
Evidence of Lying and
Drug Use
Fig. I . COMM concept mapping analysis and results conducted using the Concept System® software.
Multi-Modal Approach
Use or Restore
SELF CARE
Non-pharmacological
therapies
SELF EFFICACY
Pharmacologic
treatment
Physical activity
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Non-pharmacologic Treatment
Non-pharmacologic therapies that have proven beneficial for such
patients include acupuncture, cognitive behavioral therapy, physical
therapy, exercise therapy and therapeutic massage.2
2. Chou R, Qaseen A, Snow V, et al. Diagnosis and treatment of low back pain: a rjoint clinical practice guideline from the American
College of Physicians and the American Pain Society. Ann Intern Med 2007; 147: 478-491
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Psychosocial Intervention
Psychosocial factors are better predictors of treatment outcomes than physical findings.
Evaluation will identify factors related to poor outcomes (i.e. cognitive style, anxiety, passive attitudes towards
rehabilitation)
Fear avoidance beliefs, distress, somatization and pain catastrophizing place patients at the highest
risk for poor outcomes. 1
Primary objectives in psychosocial intervention are:
•Provide encouragement for overcoming demoralization
•Help patient make connection between thoughts, feelings and behaviors
•Teach patient coping strategies/techniques to adapt to pain and resultant
problems
1. Elder, W., King, M., Dassow, P. and Macy, B. Managing Lower back pain: You may be doing too much, The Journal of Family Practice,
2009, 58 (4). Elder, W., King, M., Dassow, P. and Macy, B. Managing Lower back pain: You may be doing too much, The Journal of Family
Practice, 2009, 58 (4).
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Non Pharmacological Options
Massage Therapy:
•Research shows massage:
•restores pleasure body (
dopamine)
•improves sleep, ( Serotonin)
•improves ROM,
•decreases pain ( Cortisol)
Recent KAN pilot study with positive results for
undifferentiated MT
Elder, W. Chronic low back pain and primary health care, 2015
•No solid data about best techniques, optimal session length, or number of treatments
so therapists need to use their clinical judgment.
45-60 min sessions (less if elderly or severely compromised)
Once or twice a week (What client can afford and how therapist works)
Client has undivided attention of LMT
And will talk about stresses or problems getting them out of their system
Many therapists include relaxation exercises during the session which clients
can follow up with at home
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Non Pharmacological Options
The LMT understands:
“No Pain No Gain” does not work for Chronic pain
Use inhibitory strokes to control the pain analyzing system and calm the
hypersensitivity
Giving the client some space from the pain
Also asking the client to document where they are having pain each session
using a body diagram and red pencil can show the client how pain changes
over time
•Establish connections to Licensed Massage Therapists
At least 3-5 years experience more if available in your area
Modalities like Swedish, Myofascial release, Neuromuscular Therapy, CranioSacral
Therapy, have been used in massage trials with good outcomes
Do they work with acute and or chronic pain?
Get a session to feel their work.
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Clinical Interview:
Conditions Suggestive of Abuse
Hepatitis
Cellulitis
HIV
Abuse?
Cardiac/
Pulmonary
disease
Trauma,
burns
STD
Chou R, et al. J Pain. 2009;10:113-130. Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed.
Newton, MA: Inflexion, Inc., 2010. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice
Guideline for Management of Opioid Therapy for Chronic Pain. 2010.
Rationale for Urine Drug Testing (UDT)
Patient Presentation
• A 38-year-old divorced mother of three
teenagers presents with complaints of lower back
pain since an MVA 4 years ago
• She describes the pain as constant, intense, and
encompassing her whole lower back area. She
relates that it is exacerbated by walking, bending,
and lifting. The pain makes activities of daily life
difficult
• She would like to have her pain reduced to a
tolerable level
Patient Work-Up
• Medical Hx
– Prior physical therapy and medication have failed
• Social Hx
– Remote history of marijuana use
– Once convicted of writing bad checks
• Family Hx
– Father abused alcohol
– Recent break-up with an abusive boyfriend with a drug problem
• Exam
– While describing the severity of her pain and her limitations, she does
not appear to be in pain
– Lower back demonstrates tenderness with some wincing
– Gait is normal
Patient Case
What is this patient’s risk of abuse, misuse, or other
aberrant behavior?
Low
Medium
High
1
2
3
4
5
6
7
⃝
⃝
⃝
⃝
⃝
⃝
⃝
Patient Case
What is the next step to refine the assessment for
risk of aberrant behavior?
⃝ Obtain prior medical records
⃝ Use an assessment tool
⃝ Confirm UDT
Special Considerations: Substance Abusers
• Periodic UDT to confirm adherence
• Regular re-evaluation to assure appropriateness of therapy
–
–
–
–
Pain severity
Functional ability
Progress toward achieving therapeutic goals
Adverse effects
• Regular clinical assessment
– Aberrant drug-related behaviors
– Substance use
– Psychological issues
• Limit prescription quantities
• Engage addiction or mental health experts
Chou R, et al. J Pain. 2009;10(2):113-130.
Special Considerations: Mental Health Issues
• Increased risk of overdose
• MH issues 3 times more prevalent in nonmedical users of
opioids
• SOAPP probes some factors
– Antisocial behaviors/history
– Psychiatric history
– Psychosocial problems
• Mental health will impact multiple aspects of treatment
– Patient reliability
– Aberrant drug-related behavior
– Adherence
Butler SF, et al. J Addict Med. 2009;3(2):66-73.
Fischer B, et al. J Pain. 2012;13(11):1029-1044.
Paulozzi LJ. J Safety Res. 2012;43(4):283-289.
Referring High-Risk Patients
Prescribers should
Understand when to
appropriately refer highrisk patients to pain
management or
addiction specialists
Regularly check your
state’s regulations for
requirements
http://www.painpolicy.wisc.edu/database-statutes-regulations-other-policies-pain-management. Accessed February 2014.
Documentation
• A risk/benefit evaluation
– History
– Physical exam
– Diagnostic testing
• Patient interactions
•
•
•
•
Previous health records, including prescriptions, MRI, CT
Patient permission to obtain records from other providers
Provider communication with other providers
Treatment plan, patient/provider agreement, informed
consent (module 3)
• Aberrant drug-related behavior
Chou R, et al. J Pain. 2009;10(2):113-130.
http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm. Accessed Jan 2014.
Module 1 Key Messages
• ER/LA opioids can be effective for pain management
• Benefit must be weighed against risk
• Medical and behavioral factors influence risk of abuse
or misuse
• Patients should be regularly assessed
• Documentation of assessments, patient interactions,
treatment plans, aberrant drug-related behavior, and
involvement of other providers is critical
Initiating Therapy, Modifying
Dosing, and Discontinuing Use
of ER/LA Opioid Analgesics
Module 2
Learning Objectives
• Appropriately assess patients for the treatment of pain with ER/LA opioid analgesics, including
analyzing risks versus potential benefits
• Assess patient’s risk of abuse, including substance use and psychiatric history
• Identify state and federal regulations on opioid prescribing
• Incorporate strategies to effectively initiate therapy, modify dosing or discontinue use
of ER/LA opioid analgesics in patients with pain
• Manage ongoing therapy with ER/LA opioid analgesics
• Incorporate effective counseling for patients and caregivers about the safe use of ER/LA opioid
analgesics
• Discuss general and product-specific drug information related to ER/LA opioid analgesics
• CAIPEC will also integrate the following Learning Objectives:
• The Epidemiology of Chronic Pain
• The Biopsychosocial Aspects of Chronic Pain
• Chronic Pain History and Shared Decision Making
• Examination and Diagnostic Testing in Patients with Chronic Pain
• Non-Pharmacologic and Pharmacologic Treatment Options
• Practice Enhancement in Managing People with Chronic Pain through a Team-based Approach
Federal & State Regulations
Federal
• Code of Federal Regulations, Title 21
Section 1306: rules governing the
issuance & filling of prescriptions
pursuant to section 309 of the Act (21
USC 829)
– www.deadiversion.usdoj.gov/21cfr/cfr/2106cfrt.htm
State
• Database of state statutes,
regulations, & policies for pain
management
– http://www.fsmb.org/pdf/grpol_pain_managem
ent.pdf
– www.medscape.com/resource/pain/opioid-
policies
• United States Code (USC) - Controlled
Substances Act, Title 21, Section 829:
prescriptions
– www.deadiversion.usdoj.gov/21cfr/21usc/829.htm
– http://statepolicyoptions.nga.org/policy_article/
database-state-statutes-regulations-and-otherofficial-governmental-policies
Analgesic and Functional Goals
• Decrease pain
– Treat underlying cause where possible
– Minimize medication use
• Restore function
– Physical, emotional, social
• Correct secondary consequences of pain
– Postural deficits, weakness, overuse
– Maladaptive behavior, poor coping
Patient Prescriber Agreements
Informed Consent
Communication process between patient and provider, including:
• Potential risks and benefits
–
–
–
–
–
–
Side effects (both short- and long-term)
Tolerance and physical dependence
Drug interactions and over-sedation
Impaired motor skills
Misuse, dependence, addiction, and overdose
Evidence of benefit
• Physician’s prescribing policies and expectations
– Number and frequency of refills
– Policy on early refills and replacement of lost or stolen medications
• Specific reasons for changing or discontinuing opioid therapy, including
violation of the treatment agreement
www.fsmb.org. Accessed Jan 2014.
Analgesic Selection
Non-opioid approaches should be considered first
• Address underlying condition
• Non-opioid analgesia
Short-acting opioids are probably safer than
ER/LA for initial therapy
• Shorter half-life
• May have a lower risk of inadvertent overdose
• Better for break-through pain
Proposed benefits of long-acting opioids
• More consistent control of pain
• Improved adherence
• Lower risk of addiction or abuse
Chou R, et al. J Pain. 2009;10:113-130.
Non-opioid medications
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NSAIDS
• 60 million Rx’s/yr
• Clinical efficacy of equipotent doses is similar
• Individual responses highly variable – especially toxicity
•
•
•
•
•
•
•
•
cox-1 vs. cox-2
naprosyn may have greatest relative cardiovascular safety profile
diclofenac - available as a topical patch for pain due to trauma and as a gel for treatment of painful joints
sulindac – increased hepatotoxicity
indomethacin - GI and central nervous system adverse effects may be more frequent or severe than with other NSAIDs
ketorolac - risk of gastropathy is increased when use exceeds five days
piroxicam – high GI toxicity
celecoxib – no antiplatelet function. Increased CV risk above 200mg/day
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Utility of NSAIDS
Variations in patient response
Generally indicated in mild to moderate pain
Mostly for pain of somatic origin although has a CNS effect as well
Each trial should last a couple weeks
May have an opioid sparing effect as adjunct
Use at the maximum anti-inflammatory dose
Protein bound – may interfere with other protein bound drugs (dilantin. coumadin)
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Tricyclic Antidepressants
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Utility in pain management
• Most useful in neuropathic pain
• May have synergy with opioids
• None of the TCA’s carries
• Switching TCA’s based on effect and/or
side effects can be tried…but often
frustrating
any indication for pain management
• Used frequently in variety
of settings
• Amitriptyline most widely studies
• Anti-depressant effects may alleviate
depression associated with chronic pain
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Mechanism of action
Side effects
• Generally unknown
• Theories involve action on serotonin,
norepinephrine receptors (TCAs with
the greatest effect upon serotonin
seem to have the greatest analgesic
effect)
• May potentiate endogenous opioid
system
• However, potent serotonin RI’s have no
analgesic effect of their own
• Can take weeks to work
Anticholinergic
(amitriptyline >
nortriptyline)
Also GI, CV, neurologic
(esp. sedation – maybe a
+’ve)
Anticholinergic and CNS
effects may diminish in
days to weeks – “ride it
out”
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Anticonvulsants
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Utility in pain management
Can be very effective, particularly in neuropathic pain
Wide variation in use among pain specialists, except with carbamazepine for
trigeminal neuralgia
Gabapentin is frequently a first choice as levels do not need monitoring
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Mechanism of
action
Theories include membrane stabilization
(phenytoin), inhibition of repeated neuronal
discharges (carbamazepine), GABA inhibition
enhancement (valproic acid, clonazepam), GABA
mimetics (gabapentin, pregabalin).
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**Benzodiazepines**
Suitable choice when anxiety complicates pain management (especially cancer
patients) and when non-pharmacological treatments unavailable
Clonazepam particularly useful in neuropathic pain (GABA potentiation)
Drawbacks well known
• Addictive potential is significant
• Potentiates sedation and respiratory depression
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Muscle relaxants & Antispasmodics
Painful muscle spasm, myoclonic jerks can accompany a variety of pain conditions
(and Opioids)
• toxicity of morphine
Mechanism of action may reflect their sedative effects more than direct muscle
effect
Commonly used – cyclobenzaprine, baclofen, methocarbamol
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SSRI/SNRI
•Often tried when TCA side effects limit utility
•May be treating depression – not an uncommon consequence of life
with chronic pain
•Venlafaxine has been shown to be similar to imipramine in one study of
painful neuropathy
•Duloxetine approved for diabetic peripheral neuropathy
•Depression is probably undertreated in chronic pain patients in general
(cancer and non-cancer pts)
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When to Consider a Trial of an ER/LA Opioid
Pain is severe
Patient failed to
adequately respond to
non-opioid &
non-drug interventions
Pain has an
adverse impact on
function or quality of
life
Potential
therapeutic benefits
outweigh potential
harms
Consider referral to pain or addiction specialist
when risks outweigh benefits
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/UCM367726.htm. Accessed April 2014.
Chou R, et al. J Pain. 2009;10:113-130.
When to Not Consider a Trial of an ER/LA Opioid
Pain is acute
Condition is
amenable to nonopioid or non-drug
interventions
Patient is at high risk
of aberrant drugrelated behaviors
Presence of
contraindications
Chou R, et al. J Pain. 2009;10:113-130.
Initiating & Titrating ER/LA Opioid Analgesics:
Opioid-Naïve Patients
Drug/Dose
Monitor
Titrate
• For naïve?
• Drug PI
• Respiratory
Depression
• 24-72
hours
• Efficacy
• Tolerability
• Adverse Effects
• Minimum
interval Drug PI
Chou R, et al. J Pain. 2009;10:113-130.
When Analgesia is Inadequate
Reassess/manage underlying condition
Address behaviors that aggravate pain
Apply other non-opioid medications
Escalate opioid dose as a trial
Consider an ER/LA opioid (if using IR opioid)
Consider opioid rotation
Converting From Immediate Release to
ER/LA Opioids
• Safety is primary
• Before conversion to a long-acting opioid, use
immediate release preparations to titrate to the
appropriate 24 hour dose
• Different approaches
A. Use opioid equianalgesic dose table (EDT, conversion
table) to switch
B. Use cross-titration
• Slowly decrease old opioid
• Slowly increase new opioid
• May take weeks to achieve proper dosing
Switching ER/LA Opioids: Rotation
Dissatisfaction
•
•
•
•
•
•
AE
Poor efficacy
Drug interactions
Route of administration
Change in clinical status
Financial or drug-availability
Weigh
•
•
•
•
Age
Clinical state
Comorbidities
Other medications
Other Drug
Fine PG, et al. J Pain Symptom Manage. 2009;38:418-425.
•
•
•
•
•
Drug sensitivities
Convenience
Improved adherence
Financial
Best dose!?!
You have decided to switch ER/LA medications.
At what dose should the second ER/LA opioid
be initiated?
⃝ Equivalent dose, from the ED table
⃝ 25–50% reduction of equivalent dose
⃝ 75% reduction of equivalent dose
⃝ Initiate as new treatment after
wash-out period
Choosing a New Dose
Calculate
equianalgesic
dose of new
opioid from
EDT
Reduce calculated equianalgesic dose
• Generally: 25–50% reduction
• Methadone: 75–90% reduction
• Use clinical judgment
~50% reduction if patient
~25% reduction if patient
• Receives a high dose of
current opioid
• Elderly or medically frail
• Is staying on current
opioid but switching to a
different administration
route
Fine PG, et al. J Pain Symptom Manage. 2009;38:418-425.
Guidelines for Opioid Rotation
If switching to methadone:
• Reduce calculated equianalgesic dose by 75–90%
• For patients on very high opioid doses, be cautious
converting to methadone ≥ 100 mg/d
‒ Consider inpatient monitoring, including serial EKG
If switching to transdermal formulation:
• Fentanyl: use equianalgesic dose ratios in the PI
• Buprenorphine: follow instructions in the PI
Fine PG, et al. J Pain Symptom Manage. 2009;38:418-425.
Guidelines for Opioid Rotation
Titrate new opioid dose
Frequently
assess:
Analgesia
AEs
Withdrawal
symptoms
Break Through Pain
• Use a short-acting, immediate release preparation at 5–15% of
total daily opioid dose
• If oral transmucosal fentanyl is used for BTP, always begin at
lowest dose
• NEVER use ER/LA opioids for BTP
Fine PG, et al. J Pain Symptom Manage. 2009;38:418-425.
Opioid Rotation: Summary
Values from
EDT
Frequently assess
initial response
†If
Patient opioid
values
“Solve” for X
Titrate dose of new opioid to
optimize outcomes
Calculate supplemental rescue
dose used for titration at
5–15% of total daily dose‡
switching to methadone, reduce dose by 75–90%
fentanyl used as rescue, begin at lowest dose irrespective of baseline opioid
‡If oral transmucosal
Fine PG, et al. J Pain Symptom Manage. 2009;38:418-425.
Always reduce
dose+
Improper Opioid Rotation Can Be Fatal
• Nearly 15,000 people die every year as a result of overdoses
involving prescription painkillers
• 5 of the 15 drugs most frequently named in FDA-reported
fatal outcomes were opioids
• Why?
–
–
–
–
–
–
Polysubstance abuse
Nonmedical use and misuse
Prescriber’s competence
Proliferation of inconsistent guidelines for opioid rotation
Use of equianalgesic tables as conversion tables
Limitations inherent in the equianalgesic dose tables
Webster LR, et al. Pain Med. 2012;13(4):562-570.
ER/LA Opioid-Induced
Respiratory Depression
Chief hazard of
opioids
• May lead to
respiratory arrest
& death
• Greatest risk after
initiation or dose
increase
• Alcohol, sedatives,
hypnotics, etc
Reduced urge to
breathe & decreased
respiration rate
Instruct patients/
family
• Symptoms
• Shallow breathing
• Call 911
• CO2 retention can
• Dangerous
exacerbate opioid
sedating effects
polypharmacy
Chou R, et al. J Pain. 2009;10:113-130.
Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 2012.
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafety
InformationforPatientsandProviders/UCM311290.pdf
Opioid Exit Strategy – Possible Paths
Patient’s behavior
consistent with drug
addiction
•
Refer for addiction
management or
comanagement
Patient unable or
unwilling to cooperate
with outpatient taper
No apparent addiction
problem
Patient able to
cooperate with officebased taper
•
•
Provide limited
and closely
monitored
prescriptions while
referring to more
intensive services
•
Taper gradually
over 1-2 months
Implement nonopioid pain
management
(psychosocial
support, CBT, PT,
non-opioid
analgesics)
CBT, cognitive behavioral therapy; PT, physical therapy.
Katz, N. Patient Level Opioid Risk Management: A Supplement to the PainEDU.org Manual. Newton, MA: Inflexxion, Inc;
2007.
Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guideline for Practitioners. 1st Edition. North Branch,
MN: Sunrise Press; 2007.
Taper Dose When Discontinuing
Avoid withdrawal symptoms in opioid dependent patients
Optimal setting
•
Outpatient in absence of unstable medical or psychiatric conditions or
unsafe patterns of behavior
•
Higher risk patients may need a more structured setting
When aberrant drug-related behaviors continue, may need
•
Close monitoring and enforced tapering or
•
Discontinued prescription and referral to detox or
•
Agonist therapy
May use a range of approaches
• Slow…10% dose reduction/week
• Rapid…25–50% reduction every few days
Chou R, et al. J Pain. 2009;10:113-130.
Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for
Management of Opioid Therapy
Taper Dose When Discontinuing
Factors that influence the reduction rate:
• Reason for discontinuation
• Medical and psychiatric comorbidities
• Initial weaning rate
– Faster at high doses (eg, > 200 mg/d morphine equivalent)
– Slower at low doses (eg, 60-80 mg/d morphine equivalent)
• Monitor withdrawal symptoms
After taper:
• Continue to treat pain with non-opioids
• Treat psychiatric disorders
• Assess for and treat addiction-related aberrant behaviors
Chou R, et al. J Pain. 2009;10:113-130.
Shared Decision Making (SDM)
• Collaborative process for doctors
and patients, to use best evidence
available while also addressing
irrational choices, weighted
according to patient values
• Respects autonomy
• Good for long term decisions in
chronic illness involving multiple
visits
Physicians trained in a SDM
approach to chronic pain report:
• self-reported change in care of patients with
chronic pain (P =.01)
• greater overall physician satisfaction (P=.002)
• more appropriate use of time (P =.02)
• self-reported completion of treatment
contracts (P =.01)
• Self-reported rates of methadone prescribing
(P =.05)
Charles, C. Soc Sci & Med. 1997 Joosten, et al. Psychother Psychosom 2008;77:219–226 Sullivan et al, J Gen Intern
Med. 2006 Apr; 21(4): 360–362.)
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Shared Decision Making Involves:
• Asking patient about preferred role in decision-making.
• Asking about values and clarifying values
• Setting goals for care and outcomes
• Negotiating in context of patient’s preferences.
Shared Decision Making Principles:
•Empathy and validation: “you’ve been through a lot.”
•Partner: “Together I want to work on…”
•Set goals: “Change will take some time.”
•Promote self-efficacy/optimism: “positive changes.”
•Buy-in: “A re you ready to take this on?”
•Explain when hit resistance
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Utilize Shared-Decision Making
Uncontrolled chronic pain is found more often in patients who
• Are passive
• Catastrophize
• Perceive an external locus of control
Counteract these by requiring the patient to make decisions and set
goals with you.
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Decisions That Can’t Be Shared
• Policies and procedures for prescriptions, refills, and monitoring
• If and when to discontinue a medication when risks or harms outweigh
benefits ↓ ↓
• Approach should still be patient-centered – Emphasize risks/benefits to
patient
More info and an online course at:
https://www.sgim.org/File%20Library/SGIM/Resource%20Library/Meeting%20Handouts/SGIM/2011/WD06handout.pdf
http://www.coperems.org/
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Module 2 Key Messages
• Best analgesic choice depends on patient and condition
− Non-opioid analgesia
− Immediate-release opioid
− ER/LA opioid
• Rotation/conversion is not an exact science but protocols
give guidance
• ER/LA are not for breakthrough pain
• Respiratory depression is rare but serious
• Opioids should be discontinued by tapering
Managing Therapy with
ER/LA Opioid Analgesics
Module 3
Learning Objectives
• Appropriately assess patients for the treatment of pain with ER/LA opioid analgesics, including analyzing risks
versus potential benefits
• Assess patient’s risk of abuse, including substance use and psychiatric history
• Identify state and federal regulations on opioid prescribing
• Incorporate strategies to effectively initiate therapy, modify dosing or discontinue use of ER/LA
opioid analgesics in patients with pain
• Manage ongoing therapy with ER/LA opioid analgesics
• Incorporate effective counseling for patients and caregivers about the safe use of
ER/LA opioid analgesics
• Discuss general and product-specific drug information related to ER/LA opioid analgesics
• CAIPEC will also integrate the following Learning Objectives:
• The Epidemiology of Chronic Pain
• The Biopsychosocial Aspects of Chronic Pain
• Chronic Pain History and Shared Decision Making
• Examination and Diagnostic Testing in Patients with Chronic Pain
• Non-Pharmacologic and Pharmacologic Treatment Options
• Practice Enhancement in Managing People with Chronic Pain through a Team-based
Approach
Analgesic and Functional Goals
• Decrease pain
– Treat underlying cause where possible
– Minimize medication use
• Restore function
– Physical, emotional, social
• Correct secondary consequences of pain
– Postural deficits, weakness, overuse
– Maladaptive behavior, poor coping
Pain Assessment
• Current pain
– Numeric rating scale
– Visual analog scale
– Faces scale
• Pain history
Patients sometimes assume that
you don’t believe their pain
complaints
• PQRS Measure #131
They may exaggerate pain scores
Pain Management
Scales
Pain Management scales used
for assessing pain include:
•Pain Assessment and
Documentation Tool (PADT)
Progress Note
Pain Assessment and Documentation Tool (PADT™)
PDI: No Disability 0__. 1__. 2__. 3__. 4__. 5__. 6__. 7 __.
8__. 9__. 10__. Worst Disability
•Pain Disability Index (PDI)
•Universal Pain Assessment tool
(Wong-Baker FACES pain rating
scale + 0-10 numeric pain
rating)
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Self-Reflection on Patient Management
How often do you use quantitative scales for pain,
functional status, and adverse events?
Never
Sometimes
Always
1
2
3
4
5
6
7
Pain
⃝
⃝
⃝
⃝
⃝
⃝
⃝
Function
⃝
⃝
⃝
⃝
⃝
⃝
⃝
AEs
⃝
⃝
⃝
⃝
⃝
⃝
⃝
CDC HRQOL Healthy Days Measure
1. Would you say that, in general, your health is:
2. Now thinking about your PHYSICAL HEALTH, which
includes physical illness and injury, for how many days
during the past 30 days was your physical health not
good?
3. Now thinking about your MENTAL HEALTH, which
includes stress, depression, and problems with
emotions, for how many days during the past 30 days
was your mental health not good?
4. During the past 30 days, for about how many days did
poor physical or mental health keep you from doing
your usual activities, such as self-care, work, or
recreation?
http://www.cdc.gov/hrqol/hrqol14_measure.htm#1. Accessed Jan 2014.
Side Effect Rating Scale: FIBSER
Frequency, Intensity, and Burden of Side Effects Rating
Frequency
Intensity
Impact
• % time
present
• None
always
• 0-6 scale
• Severity
• None
intolerable
• 0-6 scale
• Degree of
interference
• None
nonfunctional
• 0-6 scale
Wisniewski SR, et al. J Psychiatr Pract. 2006;12(2):71-79.
http://www.medscape.org/viewarticle/752781. Accessed Jan 2014.
Patient Prescriber Agreements
Informed Consent
Communication process between patient and provider, including:
• Potential risks and benefits
–
–
–
–
–
–
Side effects (both short- and long-term)
Tolerance and physical dependence
Drug interactions and over-sedation
Impaired motor skills
Misuse, dependence, addiction, and overdose
Evidence of benefit
• Physician’s prescribing policies and expectations
– Number and frequency of refills
– Policy on early refills and replacement of lost or stolen medications
• Specific reasons for changing or discontinuing opioid therapy, including
violation of the treatment agreement
www.fsmb.org. Accessed Jan 2014.
Patient Prescriber Agreements
Written Opioid Treatment Agreement
Treatment Goals
Roles Responsibilities
Pain
Function
Monitoring
Grounds for
Continuation
Medication
safeguards
Progress towards goals
Visits
Decision
Tolerable AEs
Adherence to agreement
______________________________, Patient
______________________________, Provider
Cheatle MD, et al. J Pain Symptom Manage. 2012;44(1):105-116.
_______Date
_______Date
Rationale for Urine Drug Testing (UDT)
Prior to Therapy
During Therapy
• Prior drug use
• Other drug use
• Adherence
• Legal requirement
• Grounds for referral
• Frequency per
provider
UDT Stages
SCREENING
CONFIRMATION
• Immunoassay
• Drug class
• Qualitative (+/-)
• Lab or POC
• GC/MS or LC/MS
• Specific, definitive
• Quantitative
• Lab
SAMHSA. Clinical Drug Testing in Primary Care. Technical Assistance Publication (TAP) 32. HHS Publication
No.(SMA) 12-4668. Rockville, MD: SAMHSA, 2012.
Specific Windows of Drug Detection
Drug in Urine
Time
Amphetamines
≤2d
THC
– Single use
– Chronic use
1-3 d
≤ 30 d
Benzoylecgonine after cocaine use
2-4 d
Opiates (morphine, codeine)
2-3 d
Methadone
≤3d
≤6d
– EDDP (methadone metabolite)
Benzodiazepines (depending on drug and dose)
Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.
Days to weeks
Interpretation of Confirmed Results
Positive Result
Demonstrates
recent use
• Most drugs have
detection times of 1-3 d
• Chronic use of lipidsoluble drugs: test
positive for ≥ 1 week
Does not diagnose
Can’t determine
• Drug addiction,
physical
dependence, or
impairment
• Metabolism can
alter results
• Exposure time, dose,
or frequency of use
Negative Result
Does not diagnose
diversion
May be due to maladaptive drug-taking
behavior
• More complex than
presence or absence of
a drug in urine
• Bingeing, running out early
• Other factors: eg, cessation of insurance, financial
difficulties
Milone MC. J Med Toxicol. 2012;8(4):408-416.
Interpretation of UDT Results
• Use UDT results in conjunction with other clinical
information
• Investigate unexpected results
Discuss with the lab
Discuss with the
patient
A positive result is
probably ….
a positive result.
• Document results, interpretation, and action
• May necessitate closer monitoring and/or referral
to a specialist
Screening for Substance Abuse
• Pain Assessment and Documentation Tool (PADT)
– 17 Y/N questions
– Plus pain and function sections
• Current Opioid Misuse Measure (COMM)
– 17 questions
– 5 item Likert scale
Passik SD, et al. Clin Ther. 2004;26(4):552-561.
https://www.nhms.org/node/128 Accessed Jan 2014.
Butler SF, et al. Pain. 2007;130(1-2):144-156.
http://www.painedu.org/. Accessed Jan 2014.
Recognizing Addiction
• DSM-5 Criteria for Substance Use Disorder1
≥ 2 items  Dx
– Tolerance
– Withdrawal
– Taken more/longer than intended
≥ 6 items  severe case
– Desire/unsuccessful efforts to quit use
– Great deal of time taken by activities involved in use
– Use despite knowledge of problems associated with use
– Important activities given up because of use
– Recurrent use resulting in a failure to fulfill important role obligations
– Recurrent use resulting in physically hazardous behavior (eg, driving)
– Continued use despite recurrent social problems associated with use
– Craving for the substance
• Pain Medicine Questionnaire2 (PMQ, 26 self-report items)
• Screener and Opioid Assessment for Patients with Pain3 (SOAPP, 24 self-report items)
1.
2.
3.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. Arlington,VA:
American Psychiatric Publishing(2013).
Adams LL, et al. J Pain Symptom Manage. 2004;27(5):440-459.
Butler SF, et al. Pain. 2004;112(1-2):65-75.
Case
• You have started a 49-year-old married mother of
2 grown children on a short-acting opioid for failed back
syndrome. She got little relief from the first dose
you prescribed and little relief from 3 months of a higher dose
– Your staff points out that she has requested early refills twice
• Her son calls about his mother’s treatment
• He reports that she is uncommunicative, spending more time in bed and
on the sofa, and not leaving the house for social events and church as
was her custom. This information conflicts with the patient’s reports to
you that she is
– Functioning as before
– Having lots of pain
• A random UDT is positive for your opioid and a benzodiazepine
• At the next visit the patient reports that she is
– Functioning as before
– Having lots of pain
• Her physical exam is unchanged
• You decide to speak candidly with her about her care
Confidence in Patient Management
What conclusion(s) can you make on the basis of the
UDT? (choose all that apply)




She is taking the opioid as directed
She may be abusing other drugs
She is not taking the opioid as directed
She may be addicted
Common Adverse Events
Nausea/Vomiting
• Tend to self-resolve
• Switch opioid
• Antiemetic
Sedation
• Tends to self-resolve
• Decrease dose
Constipation
Pruritus
• Laxative
• Bowel stimulant
• Switch opioid
• Tends to self-resolve
• Antihistamines
• Switch opioid
Many patients report being allergic to pain medication, especially opioids
Swegle JM, et al. Am Fam Physician. 2006;74(8):1347-1354.
Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-S120.
Universal Precautions for Prescribing
Controlled Substances
1.
2.
3.
4.
5.
Make a Diagnosis with Appropriate Differential
Psychological Assessment Including Risk of Addictive Disorders
Informed Consent
Treatment Agreement
Pre- and Post-Intervention Assessment of Pain Level and
Function
6. Appropriate Trial of Opioid Therapy +/– Adjunctive Medication
7. Reassessment of Pain Score and Level of Function
8. Regularly Assess the “Five A’s” of Pain Medicine
• Analgesia • Adverse effects
• Activity
• Aberrant behavior
• Affect
9. Periodically Review Pain Diagnosis and Comorbid Conditions,
including Addictive Disorders
10. Documentation
Adapted from Gourlay DL, et al. Pain Med. 2005;6(2):107-112.
Taking a Team-Based Approach
You need to translate this new/updated knowledge into clinical practice
Pain management is a team approach
Your staff within the clinic and
•Other professional colleagues outside the clinic
We will focus on how to re-design the way your practice manages patients
with chronic pain
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Taking a Team-Based Approach
The general categories in a chronic pain workflow:
Clinic policy and registration processes
• Clinic policies that patients sign at check in
Self-administered assessments for new and established chronic pain patients
• Selected self assessments patient complete while they wait
Clinical check-in and staff assessments
• Nursing assessments and activities in the exam room
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Taking a Team-Based Approach
The general categories in a chronic pain workflow
(continued):
Clinical assessment
• Provider H&P
Post clinical activities
• UDS, Controlled medication agreements, etc.
Post visit activities
• Referrals, diagnostic orders, follow-up on results/consults, etc.
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Step 1: Team-Based Approach
This must become a priority for your clinic
All members (front office to back staff) must be part of the re-design
process
Educate one another about pain management (use CAIPEC webcasts or
other online sources)
Educate as a team how to do the Plan-Do-Study- Act (PDSA) quality
improvement approach
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Step 2: Team-Based Approach
Now that everyone knows why it is important and on board to improve
things:
•Use the PDSA to identify something you want to improve on (ex.
Ensuring 100% of CP patients have contracts/agreement, etc.).
•Define an ultimate goal for this specific project
•Find an area (start small) that the clinic process needs to improve on
•Map out using workflows on how that process currently happens and
what needs to change
•Identify who does what in the new workflow
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Step 3: Team-Based Approach
The Plan is in place, time to execute (“Do”).
You need a way to monitor the progress and collect some data
Tweak as you go, this is normal
Pay attention and document what is working and not working
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Step 4: Team-Based Approach
Once you feel things have progressed and have collected enough
information, “Study” it:
How much better are you doing over your baseline?
What have you and the team learned
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Step 5: Team-Based Approach
Once you studied your results, you now “Act” for the next PDSA cycle:
What can we do better? What didn’t work?
What do you now add to our chronic pain management process? Prescreening tools? New standardized visit forms or templates?
All these steps are done with the clinic team
The PDSA cycle is a repetitive processes until you reach your ultimate goal
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Team-Based Approach
Developing workflows that are “live” documents that everyone has and
adheres to helps to sustain interventions
• They make people accountable for their part of the process
CAIPEC provides a toolkit with sample documents, forms, workflows, etc.
that you can adapt for your clinic
CCentral Appalachia
A Inter-Professional
I
P Pain Education
E Collaborative
C
Workflow model for clinic practice
CCentral Appalachia
A Inter-Professional
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P Pain Education
E Collaborative
C
136 | © CO*RE 2013
Module 3 Key Messages
• Set specific analgesic and functional goals
• Use a PPA as a framework
• Document discussions, patient commitments,
actions, results
• Refer patients for addiction and abuse treatment as
needed
• Identify and manage adverse events
Counseling Patients and
Caregivers about the Safe Use
of ER/LA Opioid Analgesics
Module 4
Learning Objectives
• Appropriately assess patients for the treatment of pain with
ER/LA opioid analgesics, including analyzing risks versus
potential benefits
• Assess patient’s risk of abuse, including substance use and
psychiatric history
• Identify state and federal regulations on opioid prescribing
• Incorporate strategies to effectively initiate therapy, modify
dosing or discontinue use of ER/LA opioid analgesics in
patients with pain
• Manage ongoing therapy with ER/LA opioid analgesics
• Incorporate effective counseling for patients and caregivers
about the safe use of ER/LA opioid analgesics
• Discuss general and product-specific drug information related
to ER/LA opioid analgesics
Patient Counseling Document:
The DOs of ER/LA Opioids
• READ the medication guide
–
–
–
–
Take your medicine exactly as prescribed
Store your medicine in a safe place away from children
Flush unused medicine down the toilet
Seek help if you do not understand something
• REPORT side effects
–
–
Call your health care provider
Report to the FDA at 1-800-FDA-1088
• CALL 911 or your local emergency service right away if
– You take too much medicine
– You have trouble breathing or shortness of breath
– A child has taken this medicine
• TALK to your health care provider
–
–
–
If the medication does not control your pain
About side effects
About all your medicines: Rx, OTC, vitamins, and supplements
http://www.er-la-opioidrems.com/IwgUI/rems/pcd.action. Accessed Jan 2014.
Patient Counseling Document:
The DON’Ts of ER/LA Opioids
DON’T give your medicine to others
DON’T take medicine unless it was prescribed for you
DON’T stop taking your medicine without talking to your
health care provider
DON’T break, chew, crush, dissolve, or inject your medicine
DON’T drink alcohol while taking this medicine
http://www.er-la-opioidrems.com/IwgUI/rems/pcd.action. Accessed Jan 2014.
Reflection on Clinical Practice
How do you use the ER/LA opioid prescribing
information when counseling a patient with chronic
pain? (choose all that apply)





I don’t generally refer to it
I use it to discuss dosing
I use it to discuss side effects and warnings
I use to structure the patient discussion
I give a copy to patients
http://www.accessdata.fda.gov/scripts/cder/drugsatfda. Accessed Jan 2014.
Product-Specific Information
• Drug Prescribing Information documents
include critical information
– Indications, usage
– Dosage forms and strengths, administration
– Contraindications, warnings, precautions
– Common adverse reactions, drug interactions
– Specific populations
– Counseling information, medication guide
• Easily available:
http://www.accessdata.fda.gov/scripts/cder/dru
gsatfda/index.cfm
One of your patients travels a lot and has an
irregular lifestyle. She is scrupulously
adherent; her testimony is supported by
UDTs. Airline seats and lack of exercise have
exacerbated her back pain and she has
developed tolerance to oxycodone. What is
your recommendation?
⃝ Increase her oxycodone dose
⃝ Convert to a transdermal formulation
⃝ Taper her oxycodone and seek a non-opioid analgesic
FDA Labeling Supplement Boxed Warning
Updated
August 2014
• TRADENAME exposes users to risks of addiction, abuse, and misuse, which
can lead to overdose and death. Assess each patient’s risk before prescribing,
and monitor regularly for development of these behaviors or conditions. (5.1)
• Serious, life-threatening, or fatal respiratory depression may occur. Monitor
closely, especially upon initiation or following a dose increase. Instruct patients
to swallow TRADENAME (formulation) whole to avoid exposure to a potentially
fatal dose of (active opioid). (5.2)
• Accidental consumption of TRADENAME, especially in children, can result in
fatal overdose of (active opioid). (5.2)
• For patients who require opioid therapy while pregnant, be aware that infants
may require treatment for neonatal opioid withdrawal syndrome. Prolonged
use during pregnancy can result in life-threatening neonatal opioid withdrawal
syndrome. (5.3)
For products with an interaction with alcohol, also include the following:
• Instruct patients not to consume alcohol or any products containing alcohol
while taking TRADENAME because co-ingestion can result in fatal plasma (active
opioid) levels. (5.4)
www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm367697.pdf. Accessed October 2014.
Special Warnings for Patients:
Labeling Supplement
Updated
August 2014
• Never break, chew, or crush an oral ER/LA tablet/capsule, or cut or tear
patches prior to use
–
May lead to rapid release of ER/LA opioid causing overdose and death
–
Applesauce or feeding tube may be appropriate (consult PI)
• Use of other CNS depressants with ER/LA opioids can cause overdose and
death
–
Sedative-hypnotics and anxiolytics
–
Alcohol
–
Illegal drugs
• Use other CNS depressants, including other opioids, under the instruction
of their prescriber
• Talk to your provider about your medical history, as many functions can be
impacted by ER/LA opioids
• Do not abruptly stop or reduce the ER/LA opioid dose
• After you stop taking your drug, flush any unused tablets down the toilet
www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm367697.pdf. Accessed October 2014.
Medication Guide
• Each PI contains detailed patient instructions about dosing,
custody, precautions, disposal, etc
• Lay language, should be shared with patients verbally and in
printed form
• Patient literacy and/or language barriers must be identified
and addressed
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed October 2014.
Review All Medications:
What Other Drugs Might Impact Treatment?
Alcohol
Other
Opioid
Source
PGP
Inhibitors
Opioids
CYP
Inhibitors
Inducers
Antiarrhythmics
MAO
Inhibitors
BZD
Specific Drug Interactions
Alcohol*
PGP
Inhibitors
Morphine sulfate ER (Avinza)


Morphine sulfate ER (Kadian)


Product

Benzodiazepines


MAO
Inhibitors
Class IA + III
Antiarrhythmics


Oxycodone HCl (OxyContin)
Oxymorphone HCl (Opana ER)
CYP 450
Inhibitors/
Inducers

Morphine sulfate CR (MS Contin)
Morphine sulfate ER-Naltrexone
(Embeda)
CYP 3A4
Inhibitors/
Inducers

Hydromorphone HCl (Exalgo)
Methadone (Dolophine)
Tapentadol (Nucynta ER)



Fentanyl Transdermal (Duragesic)

Buprenorphine Transdermal
(Butrans)


FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid
Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsa
ndProviders/UCM311290.pdf. Accessed January 2014.

PGP: P-glycoprotein
MAO: monoamine oxidase
*Including medications
containing alcohol
Diversion in the Home
Own the Prescriptions
• Note how many pills in each prescription
bottle or packet
• Take inventory of all prescription
drugs in your home
• Track refills for all household members
• Keep meds in a safe place, not the
bathroom cabinet
Know Their Weaknesses
• Teens: adventure
• Elderly: drug naïveté
Discard Expired or Unused Meds
Adapted from The Partnership at DrugFree.org. Rx Abuse: Not in My House.
http://notinmyhouse.drugfree.org/steps.aspx . Accessed January 2014.
Public
Awareness
Campaign
When to Discontinue Opioids
• Severe unmanageable adverse effects
• Serious or persistent nonadherence to the treatment plan
• Illegal or unsafe behaviors
• Misuse suggestive of addiction to prescribed medication
• Lack of effectiveness
• Patient preference
• Decreased level of pain in stable patients
• Goals of treatment are not met
http://www.healthquality.va.gov/cot/. Accessed Jan 2014.
Tapering Opioids: General Considerations
• Individualize; faster or slower tapering may be
warranted
• Complete evaluation prior to initiation of the taper
– Current treatment plan
– Psychological conditions
– Other relevant factors should be completed
• Clear written and verbal instructions should be
given to patients and their families to minimize
withdrawal symptoms
http://www.healthquality.va.gov/cot/. Accessed Jan 2014.
Tapering Opioids: Patients to Refer
• High risk to engage in aberrant
behaviors (eg, parasuicidal acts;
dealing/selling medications;
severe impulse control disorders)
• Complicated withdrawal
symptoms
• Opioid addiction
• Refer to an addiction or pain
specialist!
http://www.healthquality.va.gov/cot/. Accessed Jan 2014.
Tapering Opioids: Patient Considerations
• Do not treat withdrawal symptoms with opioids or
benzodiazepines after discontinuing opioids
• Consider tapering opioids in patients who have received
regularly scheduled opioids at greater than the
recommended starting doses for more than a few days
• Non-daily, as-needed opioids do not usually need tapering
• Patient-specific factors
– Risk of precipitating withdrawal
– Level of anxiety about discontinuing
– Duration of opioid therapy (longer use slower taper)
– Medical and psychological comorbidities
– Clinical need for rapid taper
http://www.healthquality.va.gov/cot/. Accessed Jan 2014.
agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Accessed Jan 2014.
Tapering Opioids: Specific Considerations
• Taper by 20–50% per week for patients who are not
addicted
• A patient needs 20% of the previous day’s dose to
prevent withdrawal symptoms
• Consider adjuvant agents such as antidepressants
to manage irritability and sleep disturbance, or
antiepileptics for neuropathic pain
• Patient on fentanyl should be rotated to a different
opioid, either long-acting morphine or methadone
– Once the patient is converted, the same guidelines will
apply
http://www.healthquality.va.gov/cot/. Accessed Jan 2014.
agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Accessed Jan 2014.
How should patients dispose of expired
or unused opioids?
Trash
Community
drug collection
Flush down
toilet
Mix with kitty
litter and put
into trash
First Choice: Community Drug Take-Back
• National Prescription Drug
Take-Back Day: “Got Drugs?”
• More than 5000 sites participate
• Check with local government for
day/location
www.fda.gov/consumer. www.awarerx.org. Accessed Jan 2014.
http://www.deadiversion.usdoj.gov/drug_disposal/takeback/index.html. Accessed January 2014.
FDA Drug Disposal Guidelines
•
•
•
•
•
Follow the prescription drug labeling
Community drug take-back programs
Container: scratch out all identifying information on the label
Do not give your medicine to friends
When in doubt, talk to your pharmacist
Dispose of unused ER/LA opioids by
flushing down the toilet
http://www.fda.gov/forconsumers/consumerupdates/ucm101653.htm. Accessed Jan 2014.
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Module 4 Key Messages
• Use a Patient Counseling Document to
communicate
• Refer to drug-specific Prescribing Information
– Includes a Medication Guide for patients
– Proper disposal of drugs
• An exit strategy is critical
– Know when to discontinue opioids
– Know how to taper opioids
– Know when to refer to a specialist
Anyone ready for a break?
General Drug Information
for ER/LA Opioid Analgesic
Products
Module 5
Learning Objectives
• Appropriately assess patients for the treatment of pain with
ER/LA opioid analgesics, including analyzing risks versus
potential benefits
• Assess patient’s risk of abuse, including substance use and
psychiatric history
• Identify state and federal regulations on opioid prescribing
• Incorporate strategies to effectively initiate therapy, modify
dosing or discontinue use of ER/LA opioid analgesics in
patients with pain
• Manage ongoing therapy with ER/LA opioid analgesics
• Incorporate effective counseling for patients and caregivers
about the safe use of ER/LA opioid analgesics
• Discuss general and product-specific drug information related
to ER/LA opioid analgesics
Drug Information Common to ER/LA
Opioid Analgesics
Limitations of usage
• Not for as-needed analgesia
• Not for mild pain or pain not
expected to persist for an extended
duration
• Not for use in treating acute pain
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Oct 2014.
Drug Information Common
to ER/LA Opioids Key Instructions
Updated
August 2014
Reserve for use in patients for whom alternative options are
ineffective, not tolerated, or inadequate
Titrate a dose that provides adequate analgesia and minimizes
adverse reactions
Times required to reach steady-state plasma concentrations are
product specific (Refer to PI for titration interval)
Continually reevaluate patient to assess pain control and adverse
effects
Consult drug PI for dosage reduction with hepatic or renal
impairment
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Oct 2014.
A 32-year-old patient who suffered
multiple fractures in a motor vehicle
accident at age 16 has chronic pain. He is
on metoprolol, NSAIDs, gabapentin, and
alprazolam but needs increased pain
relief. What is the best next step?
⃝ Taper the alprazolam before ER/LA opioid initiation
⃝ Initiate an ER/LA opioid but monitor for respiratory depression
⃝ Begin with a medication reconciliation to avoid drug-drug
interactions
⃝ Try a different non-opioid analgesic first
ER/LA Opioids: Transdermal Dosage
• Application
– Rotate location of application
– Prepare skin
 Clip (don’t shave) hair; wash only with water
• Safety
– Strenuous exertion or external heat exposure may lead
to increased absorption and possible overdose
– Monitor patients with fever for signs/symptoms of
increased opioid exposure
– Handle and dispose appropriately
 Avoid exposure of caregivers/children
– Do not cut, damage, chew or swallow
– Products with metal foil backings are not safe for MRIs
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
CNS Depressants
ER/LA Opioid
Analgesics
Concurrent Use
• Sedatives
• Hypnotics
• General anesthetics
• Antiemetics
• Phenothiazines
• Other tranquilizers
• Alcohol
↑ Risk of:
• Respiratory depression
• Hypotension
• Profound sedation
• Coma
Reduce the initial dose of one or both agents
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
Partial agonists and mixed agonist/antagonist analgesics
ER/LA Opioid
Analgesics
Concurrent Use
• Buprenorphine
• Pentazocine
• Nalbuphine
• Butorphanol
• May reduce analgesic effect
• Precipitate withdrawal
symptoms
Avoid concurrent use
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
Antiarrhythmic Agents
• Methadone
• Buprenorphine
Concurrent Use
Antiarrhythmic Agents such as:
• Class IA
– Quinidine
– Procainamide
– Disopyramide
• Class III
– Sotalol
– Amiodarone
– Dofetilide
• May cause QTc
prolongation/
arrhythmia
Avoid use of these opioids in patients
with long QT Syndrome or those
taking antiarrhythmic medications
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
CYP Inhibitors/Inducers may impact blood levels of ER/LA opioids
CYP
Inhibitors
Opioid
Levels
CYP
Inducers
Opioid
Levels
!! Consult product-specific information !!
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
Drug
Potential Risk
•
Alcohol; medications
with alcohol
•
•
Monoamine oxidase
inhibitors (MAOIs)
Diuretics
Skeletal muscle
relaxants
Anticholinergic
medications
•
Some ER opioid formulations may rapidly release opioid
when exposed to alcohol (“dose dump”)
Some drug levels may increase without dose dumping when
exposed to alcohol
See individual PI
•
Using opioids with MAOIs may increase respiratory
depression
May cause serotonin syndrome
•
Opioids can reduce diuretic efficacy by inducing ADH
•
Opioids may enhance the neuromuscular blocking action of
skeletal muscle relaxants and increase respiratory
depression
•
Concurrent use increases the risk of urinary retention and
severe constipation/paralytic ileus
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics Drug Interactions
Illicit Drugs
• A retrospective study of 21,746 patients treated with
opioids for chronic pain
• Urine samples analyzed to determine co-occurrence of illicit
drugs
–
–
–
–
13% + for THCA (tetrahydrocannabinol)
4.6% + for cocaine
1.1% + for methamphetamine
Of those using marijuana, 14% were also using cocaine or
methamphetamine
• Patients using illicit drugs and prescribed opioids are at risk
for reactions from the abused substances and from drugdrug interactions
Pesce A, et al. Pain Physician. 2010;13:283-287.
ER/LA Opioid Analgesics
Tolerance to sedating and respiratory depressant effects of
opioids is critical to the safe use of certain
products/strengths/doses
• Products used ONLY in
opioid-tolerant patients
– Transdermal fentanyl
– Hydromorphone HCl ER
• For other products,
patients must be opioid
tolerant before using
– Certain strengths
– Certain daily doses
– Refer to individual PI
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
ER/LA Opioid Analgesics
Relative Potency to Morphine
• Intended as a general guide
• Follow conversion instructions in individual PI
• Incomplete cross-tolerance and inter-patient variability
require conservative dosing when converting from 1 opioid
to another
– Halve the calculated comparable dose; titrate new opioid as needed
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311
290.pdf. Accessed Jan 2014.
Module 5 Key Messages
• Prescribers should be knowledgeable about general
characteristics, class adverse effects, and drug
interactions for ER/LA opioid analgesic products
– This information provides the foundation for
assimilation of product-specific information and the
safe/effective use of ER/LA opioid analgesics
Specific Drug Information
for ER/LA Opioid Analgesic
Products
Module 6
Learning Objectives
• Appropriately assess patients for the treatment of pain with
ER/LA opioid analgesics, including analyzing risks versus
potential benefits
• Assess patient’s risk of abuse, including substance use and
psychiatric history
• Identify state and federal regulations on opioid prescribing
• Incorporate strategies to effectively initiate therapy, modify
dosing or discontinue use of ER/LA opioid analgesics in
patients with pain
• Manage ongoing therapy with ER/LA opioid analgesics
• Incorporate effective counseling for patients and caregivers
about the safe use of ER/LA opioid analgesics
• Discuss general and product-specific drug information related
to ER/LA opioid analgesics
Informed Treatment Decisions
Consider product characteristics that align with patient needs
Drug substance
• Formulation
• Strength
Dosing interval
Key instructions
• Titration
• Limitations of usage
• Product conversion information
Specific drug interactions
Product-specific safety
concerns
Use in opioid-tolerant
patients
Potency relative to
oral morphine
DailyMed: www.dailymed.nlm.nih.gov
Drugs@FDA: www.fda.gov/drugsatfda
A Look at Different
ER/LA Opioid Analgesic Products
• Compare and contrast
– Relative potency of ER/LA opioid agents
– Dosing frequency
– Use based on opioid exposure
Oral
– Specific drug interactions
• Morphine sulfate (4)
• Specific characteristics
• Oxycodone
• Oxymorphone
• Hydromorphone
• Methadone
• Tapentadol
Transdermal
• Buprenorphine
• Fentanyl
Relative Potency to Oral Morphine
Important to consult PIs for use of opioids as first agents and for
conversion/rotation procedures
Morphine
1.0
Oxycodone
2:1
Oxymorphone
3:1
Hydromorphone Transdermal
5:1
Fentanyl
> 100:1
Dose Ratio (Oral Morphine to Other Agents)
Methadone
• Varies contingent on prior
opioid exposure
Not Established
• Buprenorphine
• Tapentadol
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Dosing Frequency
Product
Every 8 or
12 hours
Methadone (Dolophine)

Morphine sulfate CR (MS Contin)

Every
12
hours
Tapentadol (Nucynta ER)

Oxymorphone HCl (Opana ER)

Oxycodone HCl (OxyContin)

Once/Day or
Every 12 hours
Morphine sulfate ER (Kadian)

Morphine sulfate ER-Naltrexone
(Embeda)

Once/Day
Morphine sulfate ER (Avinza)

Hydromorphone HCl ER (Exalgo)

Fentanyl Transdermal (Duragesic)
Every 3
Days
Every 7
Days

Buprenorphine Transdermal

(Butrans)
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Morphine Sulfate ER-Naltrexone: Embeda
20 mg/0.8 mg, 30 mg/1.2 mg, 50 mg/2 mg, 60 mg/2.4 mg,
80 mg/3.2 mg, and 100 mg/4 mg Capsules
Dosing
•
Interval
•
•
•
Instructions •
•
•
Specific Drug
Interactions
•
Once/day or every 12 hours
Initial dose as first opioid: 20 mg/0.8 mg
Titrate using a minimum of 3-day intervals
Swallow capsules whole (do not chew, crush, or dissolve)
Crushing or chewing will release morphine, possibly resulting in fatal
overdose, and naltrexone, possibly resulting in withdrawal symptoms
May open capsule and sprinkle pellets on applesauce for patients who
can reliably swallow without chewing, use immediately
Alcoholic beverages or medications containing alcohol may result in
the rapid release and absorption of a potentially fatal dose of
morphine
PGP inhibitors (eg, quinidine) may increase the absorption/exposure
of morphine sulfate by about 2-fold
Use in Opioid
•
Tolerant Patients
100 mg/4 mg capsule is for use in opioid-tolerant patients only
Product-Specific
•
Safety Concerns
None
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Morphine Sulfate ER-Naltrexone: Embeda
20 mg/0.8 mg, 30 mg/1.2 mg, 50 mg/2 mg, 60 mg/2.4 mg,
80 mg/3.2 mg, and 100 mg/4 mg Capsules
Dosing
•
Interval
•
•
•
Instructions •
•
•
Specific Drug
Interactions
•
Once/day or every 12 hours
Initial dose as first opioid: 20 mg/0.8 mg
Titrate using a minimum of 3-day intervals
Swallow capsules whole (do not chew, crush, or dissolve)
Crushing or chewing will release morphine, possibly resulting in fatal
overdose, and naltrexone, possibly resulting in withdrawal symptoms
May open capsule and sprinkle pellets on applesauce for patients who
can reliably swallow without chewing, use immediately
Alcoholic beverages or medications containing alcohol may result in
the rapid release and absorption of a potentially fatal dose of
morphine
PGP inhibitors (eg, quinidine) may increase the absorption/exposure
of morphine sulfate by about 2-fold
Use in Opioid
•
Tolerant Patients
100 mg/4 mg capsule is for use in opioid-tolerant patients only
Product-Specific
•
Safety Concerns
None
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Oxycodone Hydrochloride CR: OxyContin
10, 15, 20, 30, 40, 60, and 80 mg Tablets
Dosing
Interval
Instructions
•
Every 12 hours
•
•
•
•
Opioid-naïve patients: initiate treatment with 10 mg every 12 hours
Titrate using a minimum of 1 to 2 day intervals
Hepatic impairment: start with one third to one half the usual dosage
Renal impairment (creatinine clearance < 60 mL/min): start with one half the usual
dosage
Consider use of other analgesics in patients who have difficulty swallowing or have
underlying GI disorders that may predispose them to obstruction.
Swallow tablets whole (do not chew, crush, or dissolve)
Take one tablet at a time, with enough water to ensure complete swallowing
immediately after placing in the mouth
•
•
•
Specific Drug
Interactions
•
•
CYP3A4 inhibitors may increase oxycodone exposure
CYP3A4 inducers may decrease oxycodone exposure
Use in Opioid
Tolerant Patients
•
Single dose greater than 40 mg or total daily dose greater than 80 mg are for use in
opioid-tolerant patients only
•
•
Choking, gagging, regurgitation, tablets stuck in the throat, difficulty swallowing the
tablet
Contraindicated in patients with gastrointestinal obstruction
•
~ 2:1 oral morphine to oxycodone oral dose ratio
Product-Specific
Safety Concerns
Relative Potency
to Oral Morphine
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Oxycodone Hydrochloride CR: OxyContin
10, 15, 20, 30, 40, 60, and 80 mg Tablets
Dosing
Interval
Instructions
•
Every 12 hours
•
•
•
•
Opioid-naïve patients: initiate treatment with 10 mg every 12 hours
Titrate using a minimum of 1 to 2 day intervals
Hepatic impairment: start with one third to one half the usual dosage
Renal impairment (creatinine clearance < 60 mL/min): start with one half the usual
dosage
Consider use of other analgesics in patients who have difficulty swallowing or have
underlying GI disorders that may predispose them to obstruction.
Swallow tablets whole (do not chew, crush, or dissolve)
Take one tablet at a time, with enough water to ensure complete swallowing
immediately after placing in the mouth
•
•
•
Specific Drug
Interactions
•
•
CYP3A4 inhibitors may increase oxycodone exposure
CYP3A4 inducers may decrease oxycodone exposure
Use in Opioid
Tolerant Patients
•
Single dose greater than 40 mg or total daily dose greater than 80 mg are for use in
opioid-tolerant patients only
•
•
Choking, gagging, regurgitation, tablets stuck in the throat, difficulty swallowing the
tablet
Contraindicated in patients with gastrointestinal obstruction
•
~ 2:1 oral morphine to oxycodone oral dose ratio
Product-Specific
Safety Concerns
Relative Potency
to Oral Morphine
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Methadone Hydrochloride: Dolophine
5 and 10 mg Tablets
Dosing Interval
Instructions
•
Every 8 to 12 hours
•
•
Initial dose in opioid non-tolerant patients: 2.5 to 10 mg
Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose
and death. Use low doses according to the table in the full prescribing information
High inter-patient variability in absorption, metabolism, and relative analgesic potency
Opioid detoxification or maintenance treatment shall only be provided in a federally
certified opioid (addiction) treatment program (CFR, Title 42, Sec 8)
•
•
•
•
Pharmacokinetic drug-drug interactions with methadone are complex
– CYP 450 inducers may decrease methadone levels
– CYP 450 inhibitors may increase methadone levels
– Anti-retroviral agents have mixed effects on methadone levels
Potentially arrhythmogenic agents may increase risk for QTc prolongation and torsade de
pointes
Benzodiazepines may increase respiratory depression
Use in Opioid
Tolerant Patients
•
Refer to full prescribing information
Product-Specific
Safety Concerns
•
•
•
•
QTc prolongation and torsade de pointe
Peak respiratory depression occurs later and persists longer than analgesic effect
Clearance may increase during pregnancy
False positive urine drug screens possible
Relative Potency
to Oral Morphine
•
Varies depending on patient’s prior opioid experience
Specific Drug
Interactions
•
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Methadone Hydrochloride: Dolophine
5 and 10 mg Tablets
Dosing Interval
Instructions
•
Every 8 to 12 hours
•
•
Initial dose in opioid non-tolerant patients: 2.5 to 10 mg
Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose
and death. Use low doses according to the table in the full prescribing information
High inter-patient variability in absorption, metabolism, and relative analgesic potency
Opioid detoxification or maintenance treatment shall only be provided in a federally
certified opioid (addiction) treatment program (CFR, Title 42, Sec 8)
•
•
•
•
Pharmacokinetic drug-drug interactions with methadone are complex
– CYP 450 inducers may decrease methadone levels
– CYP 450 inhibitors may increase methadone levels
– Anti-retroviral agents have mixed effects on methadone levels
Potentially arrhythmogenic agents may increase risk for QTc prolongation and torsade de
pointes
Benzodiazepines may increase respiratory depression
Use in Opioid
Tolerant Patients
•
Refer to full prescribing information
Product-Specific
Safety Concerns
•
•
•
•
QTc prolongation and torsade de pointe
Peak respiratory depression occurs later and persists longer than analgesic effect
Clearance may increase during pregnancy
False positive urine drug screens possible
Relative Potency
to Oral Morphine
•
Varies depending on patient’s prior opioid experience
Specific Drug
Interactions
•
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf.
Accessed Jan 2014.
Tapentadol ER: Nucynta ER
50, 100, 150, 200, and 250 mg Tablets
Dosing
Interval
Instructions
•
Every 12 hours
•
•
•
•
•
Use 50 mg every 12 hours as initial dose in opioid nontolerant patients
Titrate by 50 mg increments using a minimum of 3-day intervals
Maximum total daily dose is 500 mg
Swallow tablets whole (do not chew, crush, or dissolve)
Take one tablet at a time and with enough water to ensure complete swallowing
immediately after placing in the mouth
Dose once daily in moderate hepatic impairment with 100 mg per day maximum
Avoid use in severe hepatic and renal impairment
•
•
•
•
Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of tapentadol
Contraindicated in patients taking MAOIs
Use in Opioid
Tolerant Patients
•
No product-specific considerations
Product-Specific
Safety Concerns
•
•
Risk of serotonin syndrome
Angioedema
Relative Potency
to Oral Morphine
•
Equipotency to oral morphine has not been established
Specific Drug
Interactions
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Tapentadol ER: Nucynta ER
50, 100, 150, 200, and 250 mg Tablets
Dosing
Interval
Instructions
•
Every 12 hours
•
•
•
•
•
Use 50 mg every 12 hours as initial dose in opioid nontolerant patients
Titrate by 50 mg increments using a minimum of 3-day intervals
Maximum total daily dose is 500 mg
Swallow tablets whole (do not chew, crush, or dissolve)
Take one tablet at a time and with enough water to ensure complete swallowing
immediately after placing in the mouth
Dose once daily in moderate hepatic impairment with 100 mg per day maximum
Avoid use in severe hepatic and renal impairment
•
•
•
•
Alcoholic beverages or medications containing alcohol may result in the rapid release and
absorption of a potentially fatal dose of tapentadol
Contraindicated in patients taking MAOIs
Use in Opioid
Tolerant Patients
•
No product-specific considerations
Product-Specific
Safety Concerns
•
•
Risk of serotonin syndrome
Angioedema
Relative Potency
to Oral Morphine
•
Equipotency to oral morphine has not been established
Specific Drug
Interactions
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Fentanyl: Duragesic (continued)
12, 25, 50, 75, and 100 mcg/hr Transdermal System
Dosing
Interval
•
One transdermal system every 3 days (72 hours)
Specific Drug
Interactions
•
•
CYP3A4 inhibitors may increase fentanyl exposure
CYP3A4 inducers may decrease fentanyl exposure
Use in Opioid Tolerant
Patients
•
All doses of fentanyl are indicated for use in opioid-tolerant patients only
•
Accidental exposure due to secondary exposure to unwashed/unclothed application
site
Increased drug exposure with increased core body temperature or fever
Bradycardia
Application site skin reactions
Product-Specific
Safety Concerns
•
•
•
Relative Potency
to Oral Morphine
•
See individual product information for conversion recommendations from prior
opioid
FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 04/2013
www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290
.pdf. Accessed Jan 2014.
Module 6 Key Messages
• Safe prescribing of ER/LA opioid analgesics requires
knowledge of product-specific information
• Product factors to consider when formulating individualized
treatment plans:
Safety
Dosing
Formulation
Tolerance
Potency
Drug
interactions
Key
Instructions
Thank you for participating!
• Please take the posttest
• Please fill out the evaluation