Collaborative for REMS Education
Presented by CO*RE
Collaboration for REMS Education
www.corerems.org
Achieving Safe
Use W...
Collaborative for REMS Education
Disclosure of Relevant
Financial Relationships
Name
Commercial
Interests
Relevant
Financi...
Collaborative for REMS Education
Learning Objectives
Describe appropriate patient assessment for treatment with ER/LA opio...
Collaborative for REMS Education
Faculty Information
Bio: Edwin A. Salsitz, MD, FASAM
Dr. Edwin A. Salsitz has been an att...
Collaborative for REMS Education
Unit IV
5 | © CO*RE 20135 | © CO*RE 2013
COUNSELING PATIENTS &
CAREGIVERS ABOUT THE
SAFE ...
Collaborative for REMS Education
Use Patient
Counseling
Document to
help counsel
patients
6 | © CO*RE 2013 Collaborative f...
Collaborative for REMS Education
Counsel Patients
About Proper Use
7 | © CO*RE 2013
•  Product-specific information about
...
Collaborative for REMS Education
Counsel Patients About Proper Use,
cont’d
8 | © CO*RE 2013
Counsel patients/caregivers:
•...
Collaborative for REMS Education
Warn Patients
9 | © CO*RE 2013
Never break, chew, or crush an oral ER/LA tablet/
capsule,...
Collaborative for REMS Education
Warn Patients, cont’d
10 | © CO*RE 2013
Misuse of ER/LA opioids
can lead to death
• Take ...
Collaborative for REMS Education
Protecting the Community
11 | © CO*RE 2013
•  Sharing ER/LA opioids w/ others
may cause t...
Collaborative for REMS Education
Source of Most Recent Rx Opioids
Among Past-Year Users
12
54.2%
18.1%
16.6%
5%
3.9%
1.9%
...
Collaborative for REMS Education
Educate Patients & Families
13 | © CO*RE 2013
Rx medicines
should only
be taken when
pres...
Collaborative for REMS Education
Parents Should Set Good
Examples & Educate Teens
14 | © CO*RE 2013
 45% of parents have
...
Collaborative for REMS Education
Substances Parents Have Discussed
With Teens*
15 | © CO*RE 2013
14%
15%
15%
21%
21%
22%
2...
Collaborative for REMS Education
Educate Parents: Not in My House
16 | © CO*RE 2013
  Note how many pills in each prescri...
Collaborative for REMS Education17 | © CO*RE 2013
Educate Parents:
Not in My House, cont’d
  Do not store prescription me...
Collaborative for REMS Education
ER/LA Opioid Drug Disposal
18 | © CO*RE 2013
National Prescription Drug Take-Back Day:
“G...
Collaborative for REMS Education
Prescription drug disposal
when a program or drop
box is unavailable:
19 | © CO*RE 2013
•...
Collaborative for REMS Education
Prescription Drug Disposal
20 | © CO*RE 2013
FDA lists especially harmful medicines –
in ...
Collaborative for REMS Education
Disposal Updates
In Dec 2012, DEA published a Notice of Proposed
Rulemaking for Disposal ...
Collaborative for REMS Education
Case: Anne,
47-Year-Old Female
Anne
47-Year-Old Female
Case:
22 | © CO*RE 2013
Collaborative for REMS Education23 | © CO*RE 2013
Anne
Case:
Anne has ovarian cancer
Stable disease based
on recent imagin...
Collaborative for REMS Education
Anne: What Would You Do Next?
24 | © CO*RE 2013
Ask where she keeps her medications &
how...
Collaborative for REMS Education25 | © CO*RE 2013
Anne: Interview
Anne reports that she keeps her
medications in her purse...
Collaborative for REMS Education
Anne: What Now? Should You:
26 | © CO*RE 2013
Call the police
Stress to her the safety co...
Collaborative for REMS Education27 | © CO*RE 2013
Anne: Case Summary
Explain to Anne
•  ER/LA opioids are extremely harmfu...
Collaborative for REMS Education28 | © CO*RE 2013
Pearls for Practice
Unit 4
28 | © CO*RE 2013
Establish Informed Consent
...
Collaborative for REMS Education
Unit V
29 | © CO*RE 201329 | © CO*RE 2013
GENERAL DRUG INFORMATION
FOR ER/LA OPIOID ANALG...
Collaborative for REMS Education
General ER/LA Opioid Drug Information
30 | © CO*RE 2013
Prescribers should be knowledgeab...
Collaborative for REMS Education31 | © CO*RE 2013
For Safer Use: Know Drug
Interactions, PK, & PD
CNS depressants can pote...
Collaborative for REMS Education
Opioid Tolerant
32 | © CO*RE 2013
Tolerance to sedating & respiratory-depressant effects ...
Collaborative for REMS Education
Key Instructions: ER/LA Opioids
33 | © CO*RE 2013
FDA. Blueprint for Prescriber Education...
Collaborative for REMS Education34 | © CO*RE 201334 | © CO*RE 2013 Collaborative for REMS Education
Do not abruptly discon...
Collaborative for REMS Education
Common Drug Information for
This Class
35 | © CO*RE 2013
•  Not for use as an
as-needed a...
Collaborative for REMS Education
Transdermal Dosage Forms
36 | © CO*RE 2013
Do not cut, damage, chew, or swallow
Exertion ...
Collaborative for REMS Education
Drug Interactions Common
to this Class
37 | © CO*RE 2013
†Buprenorphine, pentazocine, nal...
Collaborative for REMS Education
Drug Information Common to
This Class
38 | © CO*RE 2013
Use in opioid-
tolerant patients
...
Collaborative for REMS Education39 | © CO*RE 2013
Pearls for Practice
Unit 5
39 | © CO*RE 2013
Patients MUST be opioid-tol...
Collaborative for REMS Education
Unit VI
40 | © CO*RE 201340 | © CO*RE 2013
SPECIFIC DRUG INFORMATION
FOR ER/LA OPIOID ANA...
Collaborative for REMS Education
Specific Characteristics
41 | © CO*RE 2013
For detailed information, refer to online PI:
...
Collaborative for REMS Education
Morphine Sulfate ER Capsules (Avinza)
Dosing interval •  Once a day
Key
instructions
•  I...
Collaborative for REMS Education
Buprenorphine Transdermal System
(Butrans)
43 | © CO*RE 2013
Dosing
interval
•  One trans...
Collaborative for REMS Education
Buprenorphine Transdermal System
(Butrans) cont’d
Drug
interactions
•  CYP3A4 inhibitors ...
Collaborative for REMS Education
Methadone Hydrochloride Tablets
(Dolophine)
Dosing
interval
•  Every 8 to 12 h
Key
instru...
Collaborative for REMS Education
Methadone Hydrochloride Tablets
(Dolophine) cont’d
Opioid-
tolerant
•  Refer to full PI
D...
Collaborative for REMS Education
Fentanyl Transdermal System
(Duragesic)
Dosing
interval
•  Every 72 h (3 d)
Key
instructi...
Collaborative for REMS Education
Fentanyl Transdermal System
(Duragesic), cont’d
Key instructions
Specific contraindicatio...
Collaborative for REMS Education
Morphine Sulfate ER-Naltrexone
Tablets (Embeda)
Dosing interval •  Once a day or every 12...
Collaborative for REMS Education
Hydromorphone Hydrochloride ER
Tablets (Exalgo)
Dosing interval •  Once a day
Key instruc...
Collaborative for REMS Education
Morphine Sulfate ER Capsules
(Kadian)
Dosing interval •  Once a day or every 12 h
Key ins...
Collaborative for REMS Education
Morphine Sulfate CR Tablets
(MS Contin)
Dosing interval •  Every 8 h or every 12 h
Key in...
Collaborative for REMS Education
Tapentadol ER Tablets (Nucynta ER)
Dosing interval •  Every 12 h
Key instructions
•  50 m...
Collaborative for REMS Education
Oxymorphone Hydrochloride ER Tablets
(Opana ER)
54 | © CO*RE 2013
Dosing interval
•  Ever...
Collaborative for REMS Education
Oxycodone Hydrochloride CR Tablets
(OxyContin)
Dosing interval •  Every 12 h
Key instruct...
Collaborative for REMS Education
Summary
56 | © CO*RE 2013
Prescription opioid abuse & overdose is a national
epidemic. Cl...
CHRONIC PAIN,
CHRONIC OPIOIDS:
IS MY PATIENT
ADDICTED?
ASAM Unit VII
Edwin Salsitz, MD, FASAM
57 | © CO*RE 2013
Complex Interactions
Opioids
Pain Addiction
58 | © ASAM 2013
Pain
“ Pain is viewed as a biopsychosocial
phenomenon that includes sensory, emotional,
cognitive, developmental, behavior...
Addiction
Public Policy Statement:
Definition of Addiction ASAM 2011
Short Definition of Addiction:
Addiction is a primary...
Pain and Addiction
No Objective Measurements
61 | © ASAM 2013
Physical Dependence
“Physical dependence is a normal and expected response to
continuous opioid therapy. Physical dependen...
Anterior Cingulate Gyrus
Opioid Sites of Action in the Brain
63 | © ASAM 2013
Locus Coeruleus
Ventral
Tegmental
Area
Amygd...
Amphetamine
Cocaine
Opiates
Cannabinoids
Phencyclidine
Ketamine
Opiates
Ethanol
Barbiturates
Benzodiazepines
Nicotine
Cann...
Hedonic Tone
Human Condition
(abnormal tone in the vulnerable to addiction)
A Delicate Balance
Altered by Psychoactive Act...
Hedonic Tone Demonstration
66 | © ASAM 2013
Opioid Dependence (DSM-IV)
(3 or more within one year)
67 | © ASAM 2013
•  Tolerance
•  Physical Dependence/Withdrawal
•  ...
Substance Use Disorder DSM-V
Severity measured by number of symptoms; 2-3 mild,
4-6 moderate, 7-11 severe
Tolerance* Withd...
Pain and Addiction
69 | © ASAM 2013
Chronic Pain
OR
Addiction
Depression
and Anxiety
Cognitive
Disturbances
Sleep
Disturba...
Pain: Psychiatric Co-Morbidity
Depression and Pain
Comorbidity-Bair,et al
Arch Intern Med.
2003;163:2433-2445
•  56 Articl...
Twelve-Month Prevalence of DSM-IV Independent Mood and
Anxiety Disorders Among Respondents with DSM-IV
Substance Use Disor...
Pain and Addiction-Psychiatric Co-
morbidity
Odds Ratios: Major Depression—3.43 Dysthymia—6.51 Panic—5.37
GAD—2.56 Problem...
Iatrogenic Addiction/Complex
Dependence
Iatrogenic addiction occurs when a patient, [with a
negative personal or family hi...
Opioid Treatment for Pain: Risk of
Addiction
74 | © ASAM 2013
Voluminous literature including multiple systematic reviews
...
Opioid Treatment for Pain:
Risk of Addiction
Development of Opioid Use Disorder (OUD) following treatment
with opioids for...
Opioids and Pain: Risk of Addiction
A Critique of Minozzi et al.’s Pain Relief and Dependence
Systematic Review Mcauliffe,...
Opioid Treatment for Pain:
Risk of Addiction
What Percentage of CNCP Patients Exposed to COT develop
Addiction and/or Aber...
Systematic Review: Opioid Treatment for
Chronic Back Pain: Prevalence, Efficacy,
and Addiction
Martell, B. Ann Intern Med....
Opioids and Pain: Evidence
AssessmentASIPP Evidence Assessment/Guidelines
Manchikanti L, et al, Pain Physician 2012;15:S1-...
Pain and Addiction
Analgesia
Activities/Function
Aberrant Behavior
Adverse Effects
Affect
Control, loss of
Compulsive use
...
Treating Pain in the Addicted Patient
•  “Pain Patients with a
coexisting SUD are among
the most challenging
patients in m...
Treating Pain in the Addicted Patient,
cont’d
82 | © ASAM 2013
UDS—consider using opioids without confusing metabolic conv...
Treating Pain in the Addicted Patient,
cont’d
83 | © ASAM 2013
Methadone—FDA approved for
both pain and addiction
Addictio...
Pain and Addiction
84 | © ASAM 2013
Pain and Addiction – ASAM REMS
85 | © ASAM 2013
e.g. (1) caffeine (2) nicotine (3) alcohol (4) opiates (5) cocaine (6) met...
Definitions: Complex Physical
Dependence
“Dependence on opioid pain treatment is not, as we once
believed, easily reversib...
Pain and Addiction – ASAM REMS
87 | © ASAM 2013
Does
Not
Necessarily
Equal
Aberrant/
Problematic
Behavior
Addiction
Pain and Addiction – ASAM REMS
88 | © ASAM 2013
Does
Not
Necessarily
Equal
Chronic Pain Suffering
Treatment of Opioid Addiction
Drug Free Recovery-Initially or Post-Medication
Medication Plus Psychosocial
Opioid Antagoni...
“…as we know, there are known
knowns, there are things we
know we know. We also know
there are known unknowns;
that is to ...
Conclusions: Known Knowns &
Unknowns
91 | © ASAM 2013
•  De Novo Iatrogenic addiction
is uncommon
•  Aberrant/Problematic
...
Principle of Balance
Dual obligation of governments and HCPs:
Establish system of controls
to prevent abuse, misuse, &
div...
93 | © ASAM 2013
Collaborative for REMS Education
Thank you for completing the post-activity
assessment for this CO*RE session.
Your partic...
Collaborative for REMS Education
Thank you!
www.core-rems.org
159 | © CO*RE 2013
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Clinical: ER/LA Opioid REMS - Achieving Safe Use While Improving Patient Care, Part 2 - Dr. Edwin Salsitz

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Cl 5 salsitz

  1. 1. Collaborative for REMS Education Presented by CO*RE Collaboration for REMS Education www.corerems.org Achieving Safe Use While Improving Patient Care – Part 2 Presented by CO*RE Collaboration for REMS Education www.core-rems.org Collaborative for REMS Education 1 | © CO*RE 2013 ER/LA OPIOID REMS:
  2. 2. Collaborative for REMS Education Disclosure of Relevant Financial Relationships Name Commercial Interests Relevant Financial Relationships : What Was Received Relevant Financial Relationships: For What Role Edwin A. Salsitz, MD, FASAM Reckitt Benckiser Honoraria Speaker Content ofActivity: ER/LAOpioid REMS:Achieving Safe Use While Improving Patient Care 2 | © ASAM 2013
  3. 3. Collaborative for REMS Education Learning Objectives Describe appropriate patient assessment for treatment with ER/LA opioid analgesics, evaluating risks and potential benefits of ER/LA therapy, as well as possible misuse. Apply proper methods to initiate therapy, modify dose, and discontinue use of ER/ LA opioid analgesics, applying best practices including accurate dosing and conversion techniques, as well as appropriate discontinuation strategies. Demonstrate accurate knowledge about how to manage ongoing therapy with ER/ LA opioid analgesics and properly use evidence-based tools while assessing for adverse effects. Employ methods to counsel patients and caregivers about the safe use of ER/LA opioid analgesics, including proper storage and disposal. 3 | © CO*RE 2013
  4. 4. Collaborative for REMS Education Faculty Information Bio: Edwin A. Salsitz, MD, FASAM Dr. Edwin A. Salsitz has been an attending physician in the Beth Israel Medical Center, Division of Chemical Dependency, since 1983, and is an Assistant Professor of Medicine at the Albert Einstein College of Medicine. He is the principal investigator of the Methadone Medical Maintenance (office-based methadone maintenance) research project. Dr. Salsitz is certified by the American Board of Addiction Medicine (ASAM), as well as by the Board of Internal Medicine and Pulmonary Disease. He has published and lectures frequently on addiction medicine topics. 4 | © CO*RE 2013
  5. 5. Collaborative for REMS Education Unit IV 5 | © CO*RE 20135 | © CO*RE 2013 COUNSELING PATIENTS & CAREGIVERS ABOUT THE SAFE USE OF ER/LA OPIOID ANALGESICS
  6. 6. Collaborative for REMS Education Use Patient Counseling Document to help counsel patients 6 | © CO*RE 2013 Collaborative for REMS Education Download: www.er-la opioidrems.com/IwgUI/rems/pdf/ patient_counseling_document.pdf Order hard copies: www.minneapolis.cenveo.com/pcd/ SubmitOrders.aspx
  7. 7. Collaborative for REMS Education Counsel Patients About Proper Use 7 | © CO*RE 2013 •  Product-specific information about the prescribed ER/LA opioid •  How to take the ER/LA opioid as prescribed •  Importance of adherence to dosing regimen, handling missed doses, & contacting their prescriber if pain cannot be controlled Explain •  Read the ER/LA opioid Medication Guide received from pharmacy every time an ER/LA opioid is dispensed •  At every medical appointment explain all medications they take Instruct patients/ caregivers to Collaborative for REMS Education FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. Available at www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression. www.erlopioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf.
  8. 8. Collaborative for REMS Education Counsel Patients About Proper Use, cont’d 8 | © CO*RE 2013 Counsel patients/caregivers: •  On the most common AEs of ER/LA opioids •  About the risk of falls, working w/ heavy machinery, & driving •  Call the prescriber for advice about managing AEs •  Inform the prescriber about AEs Prescribers should report serious AEs to the FDA: www.fda.gov/downloads/Safety/MedWatch/ HowToReport/DownloadForms/UCM082725.pdf or 1-800-FDA-1088 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf
  9. 9. Collaborative for REMS Education Warn Patients 9 | © CO*RE 2013 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 & death •  When a patient cannot swallow a capsule whole, prescribers should refer to PI to determine if appropriate to sprinkle contents on applesauce or administer via feeding tube Use of CNS depressants or alcohol w/ ER/LA opioids can cause overdose & death FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf •  Use with alcohol may result in rapid release & absorption of a potentially fatal opioid dose •  Other depressants include sedative-hypnotics & anxiolytics, illegal drugs
  10. 10. Collaborative for REMS Education Warn Patients, cont’d 10 | © CO*RE 2013 Misuse of ER/LA opioids can lead to death • Take exactly as directed • Counsel patients/caregivers on risk factors, signs, & symptoms of overdose & opioid-induced respiratory depression, GI obstruction, & allergic reactions • Call 911 or poison control 1-800-222-1222 Do not abruptly stop or reduce the ER/LA opioid use • Discuss how to safely taper the dose when discontinuing TAKE 1 TABLET BY MOUTH EVERY 12 HOURS OXYCONTIN 10 MG Qty: 60 TABLETS FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  11. 11. Collaborative for REMS Education Protecting the Community 11 | © CO*RE 2013 •  Sharing ER/LA opioids w/ others may cause them to have serious AEs –  Including death •  Selling or giving away ER/LA opioids is against the law •  Store medication safely and securely •  Protect ER/LA opioids from theft •  Dispose of any ER/LA opioids when no longer needed –  Read product-specific disposal information included w/ ER/LA opioid Caution Patients FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf
  12. 12. Collaborative for REMS Education Source of Most Recent Rx Opioids Among Past-Year Users 12 54.2% 18.1% 16.6% 5% 3.9% 1.9% 0.3% Free: friend/ relative 1 doctor Bought/took: friend/ relative Other Drug dealer >1 doctor Bought on Internet 12 | © CO*RE 2013 SAMHSA. (2012). Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-44, HHS Publication No. (SMA) 12-4713. Rockville, MD.
  13. 13. Collaborative for REMS Education Educate Patients & Families 13 | © CO*RE 2013 Rx medicines should only be taken when prescribed to you by a provider •  Taking a pill prescribed for someone else is drug abuse and illegal, “even just once” Misusing Rx drugs can be as dangerous as illegal “street” drugs Mixing Rx opioids w/ alcohol or w/ sedatives / hypnotics is potentially fatal Apa-Hall P, et al. J Sch Nurs. 2008;24(suppl):S1-16. Paulozzi LJ, et al. Pain Med. 2012;13:87-95. Webster LR, et al. Pain Med. 2011;12 Suppl 2:S26-35.
  14. 14. Collaborative for REMS Education Parents Should Set Good Examples & Educate Teens 14 | © CO*RE 2013  45% of parents have taken pain medications w/o a prescription at some point  14% have given their children pain medications w/o a prescription Parent Survey The Partnership at DrugFree.org. Abuse of Prescription Pain Medicine in Massachusetts: Attitudes and Behavior Among Parents of Teens. October, 2011. The Partnership at DrugFree.org. 2010 Partnership Attitude Tracking Survey. Teens and Parents. 2011. Teens continue to report that their parents do not talk to them about the risks of prescription drugs at the same levels of other abused substances Teen Survey
  15. 15. Collaborative for REMS Education Substances Parents Have Discussed With Teens* 15 | © CO*RE 2013 14% 15% 15% 21% 21% 22% 23% 30% 77% 81% Inhalants Steroids w/o doctor's Rx Non-Rx cold/cough medicine to get high Methamphetamine Ecstasy Heroin Any Rx drug used w/o doctor's Rx Rx pain reliever w/o doctor's Rx Cocaine/crack Marijuana Beer/alcohol 21% *As reported by teens The Partnership at DrugFree.org. 2010 Partnership Attitude Tracking Survey. Teens and Parents. 2011. % of teens whose parents have discussed
  16. 16. Collaborative for REMS Education Educate Parents: Not in My House 16 | © CO*RE 2013   Note how many pills in each prescription bottle or pill packet   Keep track of refills for all household members   If your teen has been prescribed a drug, coordinate & monitor dosages & refills   Make sure friends & relatives—especially grandparents— are aware of the risks   If your teen visits other households, talk to the families about safeguarding their medications Step 1: Monitor The Partnership at DrugFree.org. Rx Abuse: Not in My House. http://notinmyhouse.drugfree.org/steps.aspx
  17. 17. Collaborative for REMS Education17 | © CO*RE 2013 Educate Parents: Not in My House, cont’d   Do not store prescription meds in the medicine cabinet   Keep meds in a safe place (e.g., locked cabinet)   Tell relatives, especially grandparents, to lock meds or keep in a safe place   Encourage parents of your teen’s friends to secure meds Step Two: Secure   Take inventory of all prescription drugs in your home   Discard expired or unused meds Step Three: Dispose The Partnership at DrugFree.org. Rx Abuse: Not in My House. http://notinmyhouse.drugfree.org/steps.aspx
  18. 18. Collaborative for REMS Education ER/LA Opioid Drug Disposal 18 | © CO*RE 2013 National Prescription Drug Take-Back Day: “Got Drugs?” APRIL 26, 2014 Locations TBA •  Check back at http://www.deadiversion.usdoj.gov/drug_disposal/ takeback/index.html Drug drop boxes in some local police departments, to find a box near you: •  http://rxdrugdropbox.org/ or •  www.americanmedicinechest.com/ or •  www.takebacknetwork.com/local_efforts.html
  19. 19. Collaborative for REMS Education Prescription drug disposal when a program or drop box is unavailable: 19 | © CO*RE 2013 •  Take drugs out of original containers •  Mix w/ undesirable substance, e.g., used coffee grounds or kitty litter –  Less appealing to children/pets, & unrecognizable to people who intentionally go through your trash •  Place in sealable bag, can, or other container –  Prevent leaking or breaking out of garbage bag •  Before throwing out a medicine container –  Scratch out identifying info on label If take-back program or drop box unavailable, throw out in household trash FDA. How to Dispose of Unused Medicines. 2011. www.fda.gov/downloads/Drugs/ ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/ucm107163.pdf SMARxT Disposal. A prescription for a healthy planet. www.smarxtdisposal.net/index.html
  20. 20. Collaborative for REMS Education Prescription Drug Disposal 20 | © CO*RE 2013 FDA lists especially harmful medicines – in some cases fatal w/ just 1 dose – if taken by someone other than the patient •  Instruct patients to check medication guide Flush down sink/toilet if no take- back program available •  As soon as they are no longer needed –  So cannot be accidentally taken by children, pets, or others •  Includes transdermal adhesive skin patches –  Used patch worn for 3d still contains enough opioid to harm/kill a child –  Dispose of used patches immediately after removing from skin •  Fold patch in half so sticky sides meet, then flush down toilet •  Do NOT place used or unneeded patches in household trash –  Exception is Butrans: can seal in Patch-Disposal Unit provided & dispose of in the trash www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186187.htm
  21. 21. Collaborative for REMS Education Disposal Updates In Dec 2012, DEA published a Notice of Proposed Rulemaking for Disposal of Controlled Substances •  The Secure & Responsible Drug Disposal Act of 2010 would expand options to collect controlled substances from ultimate users for disposal to include: –  Take-back events –  Mail-back programs –  Collection receptacle locations 21 | © CO*RE 2013 DEA. Federal Register. 2012; 77(246):75783-817. Proposed Rules. Disposal of Controlled Substances. www.deadiversion.usdoj.gov/fed_regs/rules/2012/fr1221_8.htm Check back at www.deadiversion.usdoj.gov/ drug_disposal/
  22. 22. Collaborative for REMS Education Case: Anne, 47-Year-Old Female Anne 47-Year-Old Female Case: 22 | © CO*RE 2013
  23. 23. Collaborative for REMS Education23 | © CO*RE 2013 Anne Case: Anne has ovarian cancer Stable disease based on recent imaging Stable pain management for 1 yr w/hydromorphone ER 12 mg q24h Query your state PDMP: she has not been doctor shopping Collect urine sample: send to lab for pain management panel that includes hydromorphone, opiates, & drugs of abuse She reports no change in her pain control •  Current regimen is still effective Last 2 months she asked for a renewal prescription 5-7 days early •  When questioned did not realize she was requesting refills early
  24. 24. Collaborative for REMS Education Anne: What Would You Do Next? 24 | © CO*RE 2013 Ask where she keeps her medications & how she secures them Make her next prescription for only 2 weeks & have her bring in her pill bottles for a count at next visit Refuse to give her a refill until the “correct” time Answer 3 is correct
  25. 25. Collaborative for REMS Education25 | © CO*RE 2013 Anne: Interview Anne reports that she keeps her medications in her purse on top of the refrigerator Further questioning reveals that her niece & nephews have recently visited her home more often than usual
  26. 26. Collaborative for REMS Education Anne: What Now? Should You: 26 | © CO*RE 2013 Call the police Stress to her the safety concerns when ER/LA opioids are taken by someone for whom they are not prescribed; request she brings her prescription bottles for pill count next visit Only prescribe 2 wks of hydromorphone ER at a time & request she brings in her prescription bottles for pill counts at each visit Answer 2 is correct
  27. 27. Collaborative for REMS Education27 | © CO*RE 2013 Anne: Case Summary Explain to Anne •  ER/LA opioids are extremely harmful—can be fatal w/ just 1 dose—if taken by someone other than the patient •  She is responsible for storing medication in a safe & secure place away from children, family members, & visitors •  If she cannot safeguard her medications, you will consider an alternative therapy You will not provide early renewal of prescription again At the next visit •  UDT positive for hydromorphone (negative other drugs) •  Anne reports she –  Purchased a medication safe that same day –  Counts her medication daily –  Spoke to her sister regarding concerns about her niece/nephews
  28. 28. Collaborative for REMS Education28 | © CO*RE 2013 Pearls for Practice Unit 4 28 | © CO*RE 2013 Establish Informed Consent Counsel Patients about Proper Use Appropriate use of medication Consequences of inappropriate use Educate the Whole Team Patients, families, caregivers Tools and Documents Can Help with Counseling Use them!
  29. 29. Collaborative for REMS Education Unit V 29 | © CO*RE 201329 | © CO*RE 2013 GENERAL DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS
  30. 30. Collaborative for REMS Education General ER/LA Opioid Drug Information 30 | © CO*RE 2013 Prescribers should be knowledgeable about general characteristics, toxicities, & drug interactions for ER/LA opioid products: Can be immediately life-threatening Respiratory depression is the most serious opioid AE Should be anticipated Constipatio n is the most common long-term AE ER/LA opioid analgesic products are scheduled under the Controlled Substances Act & can be misused & abused FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  31. 31. Collaborative for REMS Education31 | © CO*RE 2013 For Safer Use: Know Drug Interactions, PK, & PD CNS depressants can potentiate sedation & respiratory depression Use w/ MAOIs may increase respiratory depression Certain opioids w/ MAOIs can cause serotonin syndrome Methadone & buprenorphine can prolong QTc interval Some ER/LA products rapidly release opioid (dose dump) when exposed to alcohol Some drug levels may increase without dose dumping Can reduce efficacy of diuretics Inducing release of antidiuretic hormone Drugs that inhibit or induce CYP enzymes can increase or lower blood levels of some opioids
  32. 32. Collaborative for REMS Education Opioid Tolerant 32 | © CO*RE 2013 Tolerance to sedating & respiratory-depressant effects is critical to safe use of certain ER/LA opioid products, dosage unit strengths, or doses Patients must be opioid tolerant before using •  Any strength of transdermal fentanyl or hydromorphone ER •  Certain strengths or daily doses of other ER products Opioid-tolerant patients are those taking at least •  60 mg oral morphine/day •  25 mcg transdermal fentanyl/hr •  30 mg oral oxycodone/day •  8 mg oral hydromorphone/day •  25 mg oral oxymorphone/day •  An equianalgesic dose of another opioid FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012 www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression. www.er-la-opioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf. 2012. FOR 1 WK OR LONGER
  33. 33. Collaborative for REMS Education Key Instructions: ER/LA Opioids 33 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf Refer to product information for titration interval Continually re-evaluate to assess maintenance of pain control & emergence of AEs Times required to reach steady-state plasma concentrations are product-specific Individually titrate to a dose that provides adequate analgesia & minimizes adverse reactions
  34. 34. Collaborative for REMS Education34 | © CO*RE 201334 | © CO*RE 2013 Collaborative for REMS Education Do not abruptly discontinueFDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf If pain increases, attempt to identify source, while adjusting dose During chronic therapy, especially for non-cancer- related pain, periodically reassess the continued need for opioids When an ER/LA opioid is no longer required, gradually titrate dose downward to prevent signs & symptoms of withdrawal in physically dependent patients Key Instructions: ER/LA Opioids, cont’d
  35. 35. Collaborative for REMS Education Common Drug Information for This Class 35 | © CO*RE 2013 •  Not for use as an as-needed analgesic •  Not for mild pain or pain not expected to persist for an extended duration •  Not for use in treating acute pain Limitations of usage See individual drug PI Dosage reduction for hepatic or renal impairment •  Intended as general guide •  Follow conversion instructions in individual PI •  Incomplete cross- tolerance & inter-patient variability require conservative dosing when converting from 1 opioid to another –  Halve calculated comparable dose & titrate new opioid as needed Relative potency to oral morphine FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  36. 36. Collaborative for REMS Education Transdermal Dosage Forms 36 | © CO*RE 2013 Do not cut, damage, chew, or swallow Exertion or exposure to external heat can lead to fatal overdose Rotate location of application Prepare skin: clip - not shave - hair & wash area w/ water Monitor patients w/ fever for signs or symptoms of increased opioid exposure FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life- threatening respiratory depression. www.er-la-opioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf. 2012. Metal foil backings are not safe for use in MRIs
  37. 37. Collaborative for REMS Education Drug Interactions Common to this Class 37 | © CO*RE 2013 †Buprenorphine, pentazocine, nalbuphine, butorphanol FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf May enhance neuromuscular blocking action of skeletal muscle relaxants & increase respiratory depression Concurrent use w/ anticholinergic medication increases risk of urinary retention & severe constipation May lead to paralytic ileus Avoid using partial agonists & mixed agonist/antagonist analgesics† together, may reduce analgesic effect or precipitate withdrawal Concurrent use w/ other CNS depressants can increase risk of respiratory depression, hypotension, profound sedation, or coma Reduce initial dose of one or both agents
  38. 38. Collaborative for REMS Education Drug Information Common to This Class 38 | © CO*RE 2013 Use in opioid- tolerant patients Contraindications •  See individual PI for products which: –  Have strengths or total daily doses only for use in opioid-tolerant patients –  Are only for use in opioid-tolerant patients at all strengths •  Significant respiratory depression •  Acute or severe asthma in an unmonitored setting or in absence of resuscitative equipment •  Known or suspected paralytic ileus •  Hypersensitivity (e.g., anaphylaxis) •  See individual PI for additional contraindications FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  39. 39. Collaborative for REMS Education39 | © CO*RE 2013 Pearls for Practice Unit 5 39 | © CO*RE 2013 Patients MUST be opioid-tolerant in order to safely take most ER/LA opioid products Be familiar with drug-drug interactions, pharmacokinetics and pharmacodynamics of ER/LA opioids Central nervous system depressants (alcohol, sedatives, hypnotics, tranquilizers, tricyclic antidepressants) can have a potentiating effect on the sedation and respiratory depression caused by opioids.
  40. 40. Collaborative for REMS Education Unit VI 40 | © CO*RE 201340 | © CO*RE 2013 SPECIFIC DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS
  41. 41. Collaborative for REMS Education Specific Characteristics 41 | © CO*RE 2013 For detailed information, refer to online PI: DailyMed at www.dailymed.nlm.nih.gov Drugs@FDA at www.fda.gov/drugsatfda Know for opioid products you prescribe: Drug substance Formulation Strength Dosing interval Specific information about product conversions, if available Specific drug interactions Key instructions Use in opioid- tolerant patients Product- specific safety concerns Relative potency to morphine FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  42. 42. Collaborative for REMS Education Morphine Sulfate ER Capsules (Avinza) Dosing interval •  Once a day Key instructions •  Initial dose in opioid non-tolerant patients is 30 mg •  Titrate using a minimum of 3-d intervals •  Swallow capsule whole (do not chew, crush, or dissolve) •  May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing; use immediately •  MDD:* 1600 mg (renal toxicity of excipient, fumaric acid) Drug interactions •  Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose •  PGP* inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant •  90 mg & 120 mg capsules for use in opioid-tolerant patients only Product- specific safety concerns •  None * MDD=maximum daily dose; PGP= P-glycoprotein 42 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  43. 43. Collaborative for REMS Education Buprenorphine Transdermal System (Butrans) 43 | © CO*RE 2013 Dosing interval •  One transdermal system every 7 d Key instructions •  Initial dose in opioid non-tolerant patients on <30 mg morphine equivalents & in mild-moderate hepatic impairment: 5 mcg/h •  When converting from 30 mg-80 mg morphine equivalents, first taper to 30 mg morphine equivalent, then initiate w/ 10 mcg/h •  Titrate after a minimum of 72 h prior to dose adjustment •  Maximum dose: 20 mcg/h due to risk of QTc prolongation •  Application •  Apply only to sites indicated in PI •  Apply to intact/non-irritated skin •  Prep skin by clipping hair; wash site w/ water only •  Rotate application site (min 3 wks before reapply to same site) •  Do not cut •  Avoid exposure to heat •  Dispose of patches: fold adhesive side together & flush down toilet FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  44. 44. Collaborative for REMS Education Buprenorphine Transdermal System (Butrans) cont’d Drug interactions •  CYP3A4 inhibitors may increase buprenorphine levels •  CYP3A4 inducers may decrease buprenorphine levels •  Benzodiazepines may increase respiratory depression •  Class IA & III antiarrythmics, other potentially arrhythmogenic agents, may increase risk of QTc prolongation & torsade de pointe Opioid- tolerant •  10 mcg/h & 20 mcg/h for use in opioid-tolerant patients only Drug-specific safety concerns •  QTc prolongation & torsade de pointe •  Hepatotoxicity •  Application site skin reactions Relative potency: oral morphine •  Equipotency to oral morphine not established 44 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  45. 45. Collaborative for REMS Education Methadone Hydrochloride Tablets (Dolophine) Dosing interval •  Every 8 to 12 h Key instructions •  Initial dose in opioid non-tolerant patients: 2.5 to 10 mg •  Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose & death. Use low doses according to table in full PI •  High inter-patient variability in absorption, metabolism, & relative analgesic potency •  Opioid detoxification or maintenance treatment only provided in a federally certified opioid (addiction) treatment program (CFR, Title 42, Sec 8) Drug interactions •  Pharmacokinetic drug-drug interactions w/ 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 & torsade de pointe •  Benzodiazepines may increase respiratory depression 45 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  46. 46. Collaborative for REMS Education Methadone Hydrochloride Tablets (Dolophine) cont’d Opioid- tolerant •  Refer to full PI Drug- specific safety concerns •  QTc prolongation & torsade de pointe •  Peak respiratory depression occurs later & persists longer than analgesic effect •  Clearance may increase during pregnancy •  False-positive UDT possible Relative potency: oral morphine •  Varies depending on patient’s prior opioid experience 46 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  47. 47. Collaborative for REMS Education Fentanyl Transdermal System (Duragesic) Dosing interval •  Every 72 h (3 d) Key instructions •  Use product-specific information for dose conversion from prior opioid •  Hepatic or renal impairment: use 50% of dose if mild/moderate, avoid use if severe •  Application −  Apply to intact/non-irritated/non-irradiated skin on a flat surface −  Prep skin by clipping hair, washing site w/ water only −  Rotate site of application −  Titrate using no less than 72 h intervals −  Do not cut •  Avoid exposure to heat •  Avoid accidental contact when holding or caring for children •  Dispose of used/unused patches: fold adhesive side together & flush down toilet 47 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  48. 48. Collaborative for REMS Education Fentanyl Transdermal System (Duragesic), cont’d Key instructions Specific contraindications: •  Patients who are not opioid-tolerant •  Management of −  Acute or intermittent pain, or patients who require opioid analgesia for a short period of time −  Post-operative pain, out-patient, or day surgery −  Mild pain Drug interactions •  CYP3A4 inhibitors may increase fentanyl exposure •  CYP3A4 inducers may decrease fentanyl exposure Opioid-tolerant •  All doses indicated for opioid-tolerant patients only Drug-specific safety concerns •  Accidental exposure due to secondary exposure to unwashed/ unclothed application site •  Increased drug exposure w/ increased core body temp or fever •  Bradycardia •  Application site skin reactions Relative potency: oral morphine •  See individual PI for conversion recommendations from prior opioid 48 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  49. 49. Collaborative for REMS Education Morphine Sulfate ER-Naltrexone Tablets (Embeda) Dosing interval •  Once a day or every 12 h Key instructions •  Initial dose as first opioid: 20 mg/0.8 mg •  Titrate using a minimum of 3-d intervals •  Swallow capsules whole (do not chew, crush, or dissolve) •  Crushing or chewing will release morphine, possibly resulting in fatal overdose, & naltrexone, possibly resulting in withdrawal symptoms •  May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately Drug interactions •  Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose •  PGP inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant •  100 mg/4 mg capsule for use in opioid-tolerant patients only Product-specific safety concerns •  None 49 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  50. 50. Collaborative for REMS Education Hydromorphone Hydrochloride ER Tablets (Exalgo) Dosing interval •  Once a day Key instructions •  Use conversion ratios in individual PI •  Start patients w/ moderate hepatic impairment on 25% dose prescribed for patient w/ normal function •  Renal impairment: start patients w/ moderate on 50% & patients w/ severe on 25% dose prescribed for patient w/ normal function •  Titrate using a minimum of 3 to 4 d intervals •  Swallow tablets whole (do not chew, crush, or dissolve) •  Do not use in patients w/ sulfite allergy (contains sodium metabisulfite) Drug interactions •  None Opioid-tolerant •  All doses are indicated for opioid-tolerant patients only Product-specific adverse reactions •  Allergic manifestations to sulfite component Relative potency: oral morphine •  ~5:1 oral morphine to hydromorphone oral dose ratio, use conversion recommendations in individual product information 50 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  51. 51. Collaborative for REMS Education Morphine Sulfate ER Capsules (Kadian) Dosing interval •  Once a day or every 12 h Key instructions •  PI recommends not using as first opioid •  Titrate using minimum of 2-d intervals •  Swallow capsules whole (do not chew, crush, or dissolve) •  May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately Drug interactions •  Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose of morphine •  PGP inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant •  100 mg & 200 mg capsules for use in opioid-tolerant patients only Product-specific safety concerns •  None 51 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM311290.pdf
  52. 52. Collaborative for REMS Education Morphine Sulfate CR Tablets (MS Contin) Dosing interval •  Every 8 h or every 12 h Key instructions •  Product information recommends not using as first opioid. •  Titrate using a minimum of 2-d intervals •  Swallow tablets whole (do not chew, crush, or dissolve) Drug interactions •  PGP inhibitors (e.g., quinidine) may increase absorption/ exposure of morphine by ~2-fold Opioid-tolerant •  100 mg & 200 mg tablet strengths for use in opioid-tolerant patients only Product-specific safety concerns •  None 52 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  53. 53. Collaborative for REMS Education Tapentadol ER Tablets (Nucynta ER) Dosing interval •  Every 12 h Key instructions •  50 mg every 12 h is initial dose in opioid non-tolerant patients •  Titrate by 50 mg increments using minimum of 3-d intervals •  MDD: 500 mg •  Swallow tablets whole (do not chew, crush, or dissolve) •  Take 1 tablet at a time w/ enough water to ensure complete swallowing immediately after placing in mouth •  Dose once/d in moderate hepatic impairment (100 mg/d max) •  Avoid use in severe hepatic & renal impairment Drug interactions •  Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of a potentially fatal dose of tapentadol •  Contraindicated in patients taking MAOIs Opioid-tolerant •  No product-specific considerations Product-specific safety concerns •  Risk of serotonin syndrome •  Angio-edema Relative potency: oral morphine •  Equipotency to oral morphine has not been established 53 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  54. 54. Collaborative for REMS Education Oxymorphone Hydrochloride ER Tablets (Opana ER) 54 | © CO*RE 2013 Dosing interval •  Every 12 h dosing, some may benefit from asymmetric (different dose given in AM than in PM) dosing Key instructions •  Use 5 mg every 12 h as initial dose in opioid non-tolerant patients & patients w/ mild hepatic impairment & renal impairment (creatinine clearance <50 mL/min) & patients >65 yrs •  Swallow tablets whole (do not chew, crush, or dissolve) •  Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth •  Titrate using a minimum of 2-d intervals •  Contraindicated in moderate & severe hepatic impairment Drug interactions •  Alcoholic beverages or medications w/ alcohol may result in absorption of a potentially fatal dose of oxymorphone Opioid-tolerant •  No product-specific considerations Product-specific safety concerns •  None Relative potency: oral morphine •  Approximately 3:1 oral morphine to oxymorphone oral dose ratio FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  55. 55. Collaborative for REMS Education Oxycodone Hydrochloride CR Tablets (OxyContin) Dosing interval •  Every 12 h Key instructions •  Opioid-naïve patients: initiate treatment w/ 10 mg every 12 h •  Titrate using a minimum of 1 to 2 d intervals •  Hepatic impairment: start w/ ⅓-½ usual dosage •  Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage •  Consider other analgesics in patients w/ difficulty swallowing or underlying GI disorders that predispose to obstruction. Swallow tablets whole (do not chew, crush, or dissolve) •  Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth Drug interactions •  CYP3A4 inhibitors may increase oxycodone exposure •  CYP3A4 inducers may decrease oxycodone exposure Opioid-tolerant •  Single dose >40 mg or total daily dose >80 mg for use in opioid- tolerant patients only Product-specific safety concerns •  Choking, gagging, regurgitation, tablets stuck in throat, difficulty swallowing tablet •  Contraindicated in patients w/ GI obstruction Relative potency: oral morphine •  Approximately 2:1 oral morphine to oxycodone oral dose ratio 55 | © CO*RE 2013 FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 8-28-2012. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf
  56. 56. Collaborative for REMS Education Summary 56 | © CO*RE 2013 Prescription opioid abuse & overdose is a national epidemic. Clinicians must play a role in prevention Know how to manage ongoing therapy w/ ER/ LA opioids Know how to counsel patients & caregivers about the safe use of ER/LA opioids, including proper storage & disposal Be familiar w/ general & product-specific drug information concerning ER/LA opioids Be familiar w/ how to initiate therapy, modify dose, & discontinue use of ER/ LA opioids Understand how to assess patients for treatment w/ ER/LA opioids
  57. 57. CHRONIC PAIN, CHRONIC OPIOIDS: IS MY PATIENT ADDICTED? ASAM Unit VII Edwin Salsitz, MD, FASAM 57 | © CO*RE 2013
  58. 58. Complex Interactions Opioids Pain Addiction 58 | © ASAM 2013
  59. 59. Pain “ Pain is viewed as a biopsychosocial phenomenon that includes sensory, emotional, cognitive, developmental, behavioral, spiritual and cultural components. ” (IASP website) “ Pain is whatever the experiencing person says it is, existing whenever he says it does. ” (McCaffrey 1968) “ An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. ” (IASP 1994) 59 | © ASAM 2013
  60. 60. Addiction Public Policy Statement: Definition of Addiction ASAM 2011 Short Definition of Addiction: Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors. Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death. 60 | © ASAM 2013
  61. 61. Pain and Addiction No Objective Measurements 61 | © ASAM 2013
  62. 62. Physical Dependence “Physical dependence is a normal and expected response to continuous opioid therapy. Physical dependence may occur within a few days of dosing with opioids, although it varies among patients. Physical dependence (indicated by withdrawal symptoms) does not mean that the patient is addicted. ” “Physical dependence is the physiological adaptation of the body to the presence of an opioid. It is defined by the development of withdrawal symptoms when opioids are discontinued, when the dose is reduced abruptly or when an antagonist (e.g., naloxone) or an agonist-antagonist (e.g., pentazocine) is administered. ” 62 | © ASAM 2013 O'Brien CP. Drug addiction and drug abuse. In: Goodman and Gilman's The pharmacological basis of therapeutics. 9th edition.
  63. 63. Anterior Cingulate Gyrus Opioid Sites of Action in the Brain 63 | © ASAM 2013 Locus Coeruleus Ventral Tegmental Area Amygdala Arcuate Nucleus Arcuate NucleusNucleus Accumbens Prefrontal Cortex Periaqueductal Gray Area
  64. 64. Amphetamine Cocaine Opiates Cannabinoids Phencyclidine Ketamine Opiates Ethanol Barbiturates Benzodiazepines Nicotine Cannabinoids Acc VTA FCX AMYG VP ABN Raphé LC GLU GABA ENK OPIOID GABA GABA GABA DYN 5HT 5HT 5HT NE HIPP PAG RETIC To dorsal horn END DA GLU Opiates ICSS OPIOID HYPOTHAL LAT-TEG BNST NE CRF OFT Mesolimbic Dopaminergic Circuit Pleasure/Reward Center H2O, Food, Sex, Parenting, Social Eliot Gardner 64 | © ASAM 2013
  65. 65. Hedonic Tone Human Condition (abnormal tone in the vulnerable to addiction) A Delicate Balance Altered by Psychoactive Activities Range: Euphoria   Dysphoria “Set” by/in the mesolimbic dopaminergic circuitry(Pleasure/Reward/Survival Center) Sense of well being, happiness, pleasure, contentment 65 | © ASAM 2013
  66. 66. Hedonic Tone Demonstration 66 | © ASAM 2013
  67. 67. Opioid Dependence (DSM-IV) (3 or more within one year) 67 | © ASAM 2013 •  Tolerance •  Physical Dependence/Withdrawal •  Larger amounts/longer period than intended •  Inability to/persistent desire to cut down or control •  Increased amount of time spent in activities necessary to obtain opioids •  Social, occupational and recreational activities given up or reduced •  Opioid use is continued despite adverse consequences
  68. 68. Substance Use Disorder DSM-V Severity measured by number of symptoms; 2-3 mild, 4-6 moderate, 7-11 severe Tolerance* Withdrawal* More use than intended Craving for the substance Unsuccessful efforts to cut down Spends excessive time in acquisition Activities given up because of use Uses despite negative effects Failure to fulfill major role obligations Continued use despite consistent social or interpersonal problems Recurrent use in hazardous situations 68 | © ASAM 2013
  69. 69. Pain and Addiction 69 | © ASAM 2013 Chronic Pain OR Addiction Depression and Anxiety Cognitive Disturbances Sleep Disturbances Functional Disability Family/ Social Problems Financial Problems Secondary Physical Problems Human Suffering Ann Quinlan-Colwell, PhD, PCSS-O Webinar 2011
  70. 70. Pain: Psychiatric Co-Morbidity Depression and Pain Comorbidity-Bair,et al Arch Intern Med. 2003;163:2433-2445 •  56 Articles(14D>P, 42P>D) •  65% with Depression (Dep.) have significant Pain •  ~50% in Pain Clinic have Dep. •  Pain negatively affects Dep. Outcomes •  Dep. associated with decreased pain mgt. 70 | © ASAM 2013
  71. 71. Twelve-Month Prevalence of DSM-IV Independent Mood and Anxiety Disorders Among Respondents with DSM-IV Substance Use Disorders Who Sought Treatment in the Past 12 Months Disorder Respondents, % (SE) Those With Any Drug Use Disorder (13.10%)* Any mood disorder 60.31 (5.86) Major Depression 44.26 (6.28) Dysthymia 25.91 (5.19) Mania 20.39 (5.17) Hypomania 2.48 (1.67) Any anxiety disorder 42.63 (5.97) Panic disorder With agoraphobia 5.92 (2.19) Without agoraphobia 8.64 (3.05) Social phobia 12.09 (3.48) Specific phobia 22.52 (4.99) Generalized anxiety disorder 22.07 (5.18) Any alcohol use disorder 55.16 (6.29) 71 | © ASAM 2013 *Data in parentheses are the percentages of respondents with the substance use disorders who sought treatment in the past 12 months. Grant B, JAMA 2004
  72. 72. Pain and Addiction-Psychiatric Co- morbidity Odds Ratios: Major Depression—3.43 Dysthymia—6.51 Panic—5.37 GAD—2.56 Problem Drugs—3.57 Problem Alcohol—.73 Conclusion: Common mental health and drug disorders are associated with initiation and use of prescribed opioids. Attention to psychiatric disorders is important when considering opioid therapy Association Between Mental Health Disorders, Problem Drug Use, and Regular Prescription Opioid Use Sullivan M.D., Arch Intern Med 2006;166:2087-2093 Healthcare for Communities waves 1998 and 2001 N=6430 telephone survey Association of common mental health disorders in 1998 with regular Opioid Rx. Use in 2001 72 | © ASAM 2013
  73. 73. Iatrogenic Addiction/Complex Dependence Iatrogenic addiction occurs when a patient, [with a negative personal or family history for alcohol or drug addiction or abuse]*, is appropriately prescribed a controlled substance & subsequently in the therapeutic course meets the diagnostic criteria for addiction to that substance. * There is controversy about the validity of this modifier 73 | © ASAM 2013 Heit HA, Gourlay DL. Treatment of Pain in Substance Abuse Disordered Population. Ballantyne JC, Rathmell JP, Fishman SM (eds). Bonica’s Management of Pain. 4th ed. Lippincott Williams & Wilkins. In Press.
  74. 74. Opioid Treatment for Pain: Risk of Addiction 74 | © ASAM 2013 Voluminous literature including multiple systematic reviews Rates vary widely 0%-50%-- higher in those with addiction hx Often not clear how the diagnosis of addiction is confirmed Aberrant and Problematic Behaviors often considered to make a diagnosis of addiction Diagnosis is often not clear when opioids are prescribed for pain by HCP—lack of education in addictive disease Clinical expertise and individualization required. ASAM members uniquely qualified
  75. 75. Opioid Treatment for Pain: Risk of Addiction Development of Opioid Use Disorder (OUD) following treatment with opioids for pain Minozzi S, et al. Addiction 2012; “The most impressive finding of the present review is the deficiency of good-quality studies.” 75 | © ASAM 2013 Systematic review of 17 studies (N=88,235) including 3 systematic reviews, 1 RCT, and 12 observational studies Results: Incidence = 0-24% (median 0.5%); prevalence = 0-31% (median 4.5%) Conclusion: Opioids for chronic pain are not associated with a major risk for developing an OUD
  76. 76. Opioids and Pain: Risk of Addiction A Critique of Minozzi et al.’s Pain Relief and Dependence Systematic Review Mcauliffe, W. Addiction, 108. 1162-1171 2013 •  “This critique concurs with authors who have concluded that existing research is inadequate for estimating the rate of iatrogenic addiction in patients treated for non-cancer pain.” •  “Systematic reviews of many irrelevant, inadequate, and incomparable studies cannot substitute for properly designed studies” 76 | © ASAM 2013
  77. 77. Opioid Treatment for Pain: Risk of Addiction What Percentage of CNCP Patients Exposed to COT develop Addiction and/or Aberrant drug-Related Behaviors? A Structured Evidence-Based Review. Fishbain et al Pain Med 2008 •  24 studies COT, 26.2 mos. (n=2,507), average % addiction= 3.27% •  17% of studies pre-selected for no current/past hx. of addiction/abuse addiction in pre-selected 0.19% vs. 5.0% in non-selected •  Average % ADRBs =11.5% , pre-selected= 0.59% •  UDS, 5 studies n=15,442, ADRBs = 20% no opioid/other non-Rx opioid •  UDS, illicit drugs non-opioid, 14.5% Conclusions: The results of this evidence-based structured review indicate that COT exposure will lead to abuse/addiction in a very small % of patients. This % can be dramatically decreased by preselecting CPPs for no previous/ current hx of drug/alcohol abuse/addiction 77 | © ASAM 2013
  78. 78. Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Addiction Martell, B. Ann Intern Med. 2007;146:116-127Conclusion: Opioids are commonly prescribed for chronic back pain and may be efficacious for short-term pain relief. Long-term efficacy (>16 weeks) is unclear. Substance use disorders are common in patients taking opioids for back pain, and aberrant medication-taking behaviors occur in up to 24%. Concept of “Adverse Selection”
  79. 79. Opioids and Pain: Evidence AssessmentASIPP Evidence Assessment/Guidelines Manchikanti L, et al, Pain Physician 2012;15:S1-S66 Selected Conclusions: •  Limited evidence that screening for opioid abuse using an instrument reduces abuse  Recommended •  Good Evidence that UDS reduces abuse of Rx opioids •  Good to Fair evidence that Prescription Monitoring Programs reduce drug abuse of doctor shopping •  Fair evidence that Prescription Monitoring Programs reduce ED visits, overdoses, or deaths 79 | © ASAM 2013
  80. 80. Pain and Addiction Analgesia Activities/Function Aberrant Behavior Adverse Effects Affect Control, loss of Compulsive use Craving drug Continued use Chronic problem Pain – 5 A’s Addiction – 5 C’s 80 | © ASAM 2013
  81. 81. Treating Pain in the Addicted Patient •  “Pain Patients with a coexisting SUD are among the most challenging patients in medicine.” •  Awareness of potential deception in pt’s history •  Universal Precautions •  ?? “Real Pain” may make opioids less rewarding/ euphorogenic •  Screening Tests: ORT, SOAPP, others •  Untreated Pain is a trigger for relapse •  Address both pain and addiction •  Significant other to secure and dispense opioid meds •  Active recovery program •  UDS, pill counts, agreements, etc. 81 | © ASAM 2013 Bailey, et al. Pain Medicine 2010; 11: 1803-1818
  82. 82. Treating Pain in the Addicted Patient, cont’d 82 | © ASAM 2013 UDS—consider using opioids without confusing metabolic conversions to other non- prescribed opioid analgesics: oxycodone  oxymorphone (hydromorphone, methadone) No poppy seeds Opioid agreement Avoid other potentially abusable medications: benzos, hypnotics, muscle relaxants, etc Identify and treat psychiatric co-morbidity— common in both This review does not discuss the management of pain, requiring chronic opioids, in the context of active or ongoing addiction. Bailey, et al. Pain Medicine 2010; 11: 1803-1818
  83. 83. Treating Pain in the Addicted Patient, cont’d 83 | © ASAM 2013 Methadone—FDA approved for both pain and addiction Addiction dosing q 24 hours: Analgesic dosing q 6-8 hours MMTPs/OTPs not authorized to treat pain MMTPs not able to provide 3-4 doses per day for pain/addiction MMTPs “take homes” take time Prescribing methadone for addiction not legal—CSA Buprenorphine pharmacotherapy: formulations approved for addiction and for pain. OBOT waivered physicians Judicious use of non-opioid medications Psychosocial modalities: MI, CBT,Accupunture, Meditation, etc. Wachholtz, et al. Substance Abuse and Rehabilitation 2011:2 145--162
  84. 84. Pain and Addiction 84 | © ASAM 2013
  85. 85. Pain and Addiction – ASAM REMS 85 | © ASAM 2013 e.g. (1) caffeine (2) nicotine (3) alcohol (4) opiates (5) cocaine (6) methadone Does Not Necessarily Equal Physical Dependence Addiction
  86. 86. Definitions: Complex Physical Dependence “Dependence on opioid pain treatment is not, as we once believed, easily reversible; it is a complex physical and psychological state that may require therapy similar to addiction treatment, consisting of structure, monitoring, and counseling, and possibly continued prescription of opioid agonists. Whether or not it is called addiction, complex persistent opioid dependence is a serious consequence of long term pain treatment that requires consideration when deciding whether to embark on long term opioid pain therapy as well as during the course of such therapy. Opioid Dependence vs Addiction A Distinction Without a Difference? Ballantyne J, Sullivan M, Kolodny A, Arch Intern Med, 2012 86 | © ASAM 2013
  87. 87. Pain and Addiction – ASAM REMS 87 | © ASAM 2013 Does Not Necessarily Equal Aberrant/ Problematic Behavior Addiction
  88. 88. Pain and Addiction – ASAM REMS 88 | © ASAM 2013 Does Not Necessarily Equal Chronic Pain Suffering
  89. 89. Treatment of Opioid Addiction Drug Free Recovery-Initially or Post-Medication Medication Plus Psychosocial Opioid Antagonist Therapy: Naltrexone Tablets and Depot I.M. Opioid Full/Partial Agonist Therapy: Methadone, Buprenorphine Medication Assisted: Therapy, Treatment, Recovery 89 | © ASAM 2013
  90. 90. “…as we know, there are known knowns, there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don’t know we don’t know.” – Donald Rumsfeld The Clinical Conundrum 90 | © ASAM 2013
  91. 91. Conclusions: Known Knowns & Unknowns 91 | © ASAM 2013 •  De Novo Iatrogenic addiction is uncommon •  Aberrant/Problematic Behaviors are common •  Risks are highest in those with current/past history of addiction •  Both Pain and Addiction must be addressed and treated •  Monitoring patients, using Universal Precautions is helpful •  Follow the FSMBs guidelines to avoid any regulatory problems •  Is it a “Pain Case Gone Bad” or Addiction—often Grey Zone •  Psychiatric Co-Morbidities and Suffering are common •  Challenging Clinical Cases— Requires Individualization Tx •  Everyone is innocent until proven guilty
  92. 92. Principle of Balance Dual obligation of governments and HCPs: Establish system of controls to prevent abuse, misuse, & diversion of CS--opioids Ensure medical availability 92 | © ASAM 2013 Pain & Policy Studies Group. Achieving Balance in State Pain Policy: A Progress Report Card. 3rd ed. 2007.
  93. 93. 93 | © ASAM 2013
  94. 94. Collaborative for REMS Education Thank you for completing the post-activity assessment for this CO*RE session. Your participation in this assessment allows CO*RE to report de-identified numbers to the FDA. A strong show of engagement will demonstrate that clinicians have voluntarily taken this important education and are committed to patient safety and improved outcomes. 94 | © CO*RE 2013 IMPORTANT! THANK YOU!
  95. 95. Collaborative for REMS Education Thank you! www.core-rems.org 159 | © CO*RE 2013

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