frontline pharmacist · inverts traditional usage of iatrogenic harm largely perpetuated by...
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Frontline Pharmacist: The Opioid Epidemic with a Focus on
TreatmentANNIE OTTNEY, PHARMD, BCPS
FEBRUARY 25, 2018
Learning Objectives
Pharmacist
Explain how to interpret a urine drug screen
Develop a discontinuation plan for a patient misusing opioids
Identify resources for patients with opioid use disorder
Describe the role of medication-assisted treatment in patients with opioid use
disorder
Learning Objectives
Pharmacy Technician
Describe common issues with interpretation of a urine drug screen
List medications that can be used for supportive care when discontinuing
opioids
Identify resources for patients with opioid use disorder
State medications that are used in medication-assisted treatment for opioid use
disorder
Urine Drug Screening
CDC recommends UDS before initiating opioids and at least ANNUALLY
thereafter (consider Opioid Risk Tool)
Urine preferred due to convenience and longer duration of detectability
Random screening preferred
Opioid Risk Tool
Score Risk Level
3 or less Low
4 to 7 Moderate
8 or higher High
Image from: https://www.drugabuse.gov/sites/default/files/files/OpioidRiskTool.pdf
Urine Drug Screening
Risk Category Recommended Screening
Frequency
Low risk by ORT Periodic (up to 1/year)
Moderate risk by ORT Regular (up to 2/year)
High risk by ORT or opioid doses > 120
MME/day
Frequent (up to 3 to 4/year)
Aberrant behavior At time of visit
Washington State Agency Medical Directors’ Group.
http://www.agencymeddirectors.wa.gov/files/opioidgdline.pdf
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Urine Drug Screening
DO’s
Have a plan in place ahead of time on how to address unexpected results
Include patient in conversation before and after screening
DON’Ts
Make assumptions
Abandon the patient
Drug-Specific Interpretation
Test drug or drug
category
Duration of detectability Drugs that may cause false positive
screening
Amphetamines • 48 hours Amantadine, bupropion, chlorpromazine, desipramine, fluoxetine,
L-methamphetamine, labetalol,
methylphenidate, phentermine, phenylephrine, promethazine,
pseudoephedrine, ranitidine, thioridazine, trazodone
Benzodiazepines • Short-acting = 3 days• Long-acting = 30 days
Oxaprozin, sertraline
Cocaine • 2 to 3 days with occasionaluse
• Up to 8 days with heavy use
Topical anesthetics containing cocaine
Opiates • 2 to 4 days Dextromethorphan, diphenhydramine, fluoroquinolones, poppy seeds, quinine,
rifampin, verapamil
Phencyclidine • 8 days Dextromethorphan, diphenhydramine, ibuprofen, imipramine, ketamine,
meperidine, thioridazine, tramadol,
venlafaxine
Marijuana • 3 days with single use• 5 to 7 days with use around 4
times/week
• 10 to 15 days with daily use• >30 days with long-term,
heavy use
Dronabinol, NSAIDs (esp. naproxen, ibuprofen, and sulindac), proton-pump
inhibitors
Moeller KE.Mayo Clin Proc. 2008;83:66-76.
Opioid Inactive metabolites Active metabolites
identical to
pharmaceutical
opioids
Active metabolites that
are not
pharmaceutical
opioids
Morphine Normorphine Hydromorphone Morphine-3-G-
glucuronide
Morphine-6-G-
glucuronide
Hydromorphone Minor metabolites None Hydromorphone-3-
glucuronide
Hydrocodone Norhydrocodone Hydromorphone None
Codeine Norcodeine Hydrocodone
Morphine
None
Oxycodone None Oxymorphone Noroxycodone
Oxymorphone Oxymorphone-3-
glucuronide
None 6-Hydroxy-
oxymorphone
Fentanyl Norfentanyl None None
Tramadol Nortramadol None O-desmethyltramadol
Methadone EDDP and EMDP None None
Heroin Normorphine Morphine 6-Monoacetylmorphine
Smith HS.Mayo Clin Proc.2009;84:613-624.
Benzodiazepine Metabolites
Alprazolam Alpha-OH-alprazolam
Diazepam Nordiazepam,
oxazepam, temazepam
Clonazepam 7-aminoclonazepam
Lorazepam Lorazepam-glucuronide
All benzos are extensively metabolized = parent
compounds not detected in the urine
Mayo Clinic Medical Laboratories.
Benzodiazepine confirmation, urine.
Urine Drug Screening-Patient Case #1
A 48 year-old female patient with
chronic back pain has been taking
hyrdrocodone/APAP 10/325 mg-4
tablets daily. Her last reported dose
was this morning.
How would you interpret the urine
drug screen?
Drug Result
Amphetamines
Methamphetamine Detected
Opiates
Hydrocodone Detected
Hydromorphone Detected
Norhydrocodone Detected
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Urine Drug Screening-Patient Case #2
A 45-year old female has been on
methadone 10 mg three times daily
and alprazolam 0.5 mg twice daily for
the previous 5 years. Her last reported
doses were this morning.
How would you interpret the urine
drug screen?
Drug Result
Benzodiazepines
Alpha-OH-alprazolam Not detected
Alprazolam Detected
Opiates
Methadone Detected
EDDP Not detected
Urine Drug Screening-Patient Case #3
A 56-year old male has been on
hydrocodone/APAP 10/325 mg- 5
tablets daily and diazepam 5 mg
three times daily for the previous 7
years. His last fill of the diazepam was
2 months ago (#90 tablets) and last fill
of hydrocodone/APAP was 3 weeks
ago (#150 tablets).
How would you interpret the urine
drug screen?
Drug Result
Benzodiazepines
Nordiazepam Not detected
Temazepam Not detected
Oxazepam Not detected
Opiates
Hydrocodone Not detected
Hydromorphone Not detected
Norhydrocodone Not detected
Opioid Discontinuation
Action Situation
Immediate discontinuation Threatening behavior; confirmation of diversion,
multisourcing, or prescription forgery; confirmation of illicit
drug use; overdose
Rapid tapering Frequent requests for early refills despite adequate titration
or long-acting opioids; major adverse effects or intoxication;
opioid-induced hyperalgesia; other non-adherence
Gradual tapering Functional goals not met; morphine equivalent dosage
greater than 100 mg per day without clear benefit to
function or pain; persistent adverse effects despite opioid
rotation; patient preference
Berland D.Am Fam Physician 2012;86:252-258.
Opioid Discontinuation
Mr. Y is a 45 year old male with a history of chronic migraines due to a
traumatic brain injury.
He has been on fentanyl 75 mcg/hr patches for 4 years and desires to
decrease his use of opioid medications.
How should this patient be tapered?
Opioid Discontinuation
How to taper—individualize
Daily dose to prevent withdrawal is approximately 25% of the previous
day’s dose
E.g. Oxycodone 80 mg daily reduce by no more than 20 mg
Decrease dose by 10% of original dose every 5 to 7
days
Dose at 30% of original dose
Continue to decrease by 10%
of remaining dose weekly
Berna C. Mayo Clin Proc.2015;90:828-842.
Week 1: Morphine ER 160 mg/day
Week 5: Morphine ER 80 mg/day
Week 6: Morphine ER 60 mg/day
Fentanyl 75 mcg/hour Morphine ER 180 mg/day
Week 11: Morphine ER 15 mg/day
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Opioid Discontinuation
A 43 year-old female has been on
oxycodone/ APAP 10/325 mg-3
tablets daily for the last year. She
frequently calls the office for early
refills and cancels follow-up
appointments last minute.
Her prescriber would like to taper her
off the opioid and switch to
alternative pain medications.
Oxycodone 30 mg/day
Oxycodone 20 mg/day
Prescribe oxycodone 5 mg
tablets
Oxycodone 10 mg/day
Oxycodone 5 mg/day
Days 1-5
Days 6-8
Days 9-11
Discontinue
Opioid Discontinuation
Acute withdrawal
Symptoms are similar to a severe case of influenza
Not life-threatening
Managed with supportive therapy
Increase in pain?
VA study showed 70% of patients being tapered had no change or less pain compared to baseline
Pain due to withdrawal should resolve after first week
Harden P. Pain Med.2015;16:1975-1981.
Opioid Discontinuation
Clonidine
Opioid withdrawal is largely due to overactivity of noradrenergic system
Alpha-2 agonists activate presynaptic alpha-2 receptors, reducing sympathetic
activity
Opioid Discontinuation
Symptomatic management of opioid withdrawal
Medication Indication
Clonidine* Anxiety, restlessness, dysphoria
Hydroxyzine Anxiety, lacrimation, and rhinorrhea
Diphenhydramine Nausea, vomiting, restlessness,
insomnia
Ondansetron Nausea
Loperamide* Diarrhea, stomach cramps
Acetaminophen, ibuprofen Pain, myalgia
Trazodone Insomnia
*Usually not needed for gradual taper
Terminology
Addiction
Compulsive drug use despite harmful consequences
Euphoria crash craving
“Pseudoaddiction”??
Physical dependence
Tolerance and withdrawal
Opioid Use Disorder
Addiction
Historically reported to be rare (<1%) in patients being prescribed prescription
opioids
Current estimates indicate between 3-26% of chronic pain patients on
opioids have opioid use disorder
Dowell D, et al.MMWR Recomm Rep.2016;65(No.1).
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Opioid Use Disorder
Porter & Jick
New England Journal of Medicine, Letter to the Editor, 1980
“Although there were 11,882 patients who received at least one narcotic preparation,
there were only four cases of reasonably well documented addiction in patients who had no history of addiction.”
439 indexed citations to letter as evidence addiction to opioids was rare
Porter J, et al. N Engl J Med.1980;302:123.
Opioid Use Disorder
Pseudoaddiction
Quarter century term that has never been empirically verified
Single case report from 1989 of hospitalized 17-year old with acute leukemia
Inverts traditional usage of iatrogenic harm
Largely perpetuated by pharmaceutical industry in medical literature
Pain and addiction are NOT mutually exclusive conditions
Greene MS, et al. Curr Addict Rep.2015;2(4):310-317.
Opioid Use Disorder
Diagnostic criteria
At least 2 of the following in a 12 month period:
Larger amount or over longer period of time than intended
Persistent desire or unsuccessful attempts to cut down or control use
Great deal of time spent in activities relating to opioid use
Cravings
Failure to fulfill major obligations at work, school, or home
Continued use despite social or interpersonal problems
Important social, occupational, or recreational activities compromised due to use
Use in situations where it is physically hazardous
Continued use despite knowledge of the problem
Tolerance
Withdrawal
Opioid Use Disorder
Validated questionnaires for opioid misuse in chronic pain patients
Abbreviation Description
COMM (Current Opioid Misuse Measure) 17 items, less than 10 minutes, self-
reported
ABC (Addiction Behaviors Checklist) 20 items, 10 minutes, clinician
observed checklist
Chabal 5-point checklist 5 items, less than 2 minutes, patient
interview
PMQ (Pain Medication Questionnaire) 26 items, 10 minutes, self-reported
PADT (Pain Assessment & Documentation
Tool)
41 items, 10 minutes, patient
interview
All tools available at: http://www.opioidrisk.com/node/775
0 10 20 30 40 50 60 70 80
Type 1 diabetes
Drug addiction
Hypertension
Asthma
Percentage of Patients Who Relapse
50% to 70%
50% to 70%
40% to 60%
30% to 50%
National Institute on Drug Abuse. Principles of Drug Addiction Treatment: A Research-Based
Guide (3rd ed).
Treating Opioid Use Disorder
Medication assisted treatment (MAT)
Combination of medications and behavioral counseling to treat “whole
person”
Benefits of treatment
Prevents withdrawal
Decreases illicit drug use
Reduces criminal activity
Improves social functioning
Decreases infectious disease risks
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•MethadoneAgonist
• Buprenorphine
• Buprenorphine/ naloxonePartial agonist/
antagonist
•NaltrexoneAntagonist
Treating Opioid Use Disorder
Methadone
Mechanism
Full mu-receptor agonist
Occupies brain receptor sites affected by heroin and other opiates with stable
dosing, does not cause euphoria or intoxication
Administered as liquid or dispersible tablet
Only available through Opioid Treatment Program
SAMHSA Treatment Locator:
https://dpt2.samhsa.gov/treatment/directory.aspx
Treating Opioid Use Disorder
Methadone
Advantages Disadvantages
Requires daily trip to receive dose
Effective More respiratory depression and
sedation than buprenorphine
Safe in pregnancy QT prolongation/ drug interactions
Treating Opioid Use Disorder
Buprenorphine
Mechanism
Partial mu agonist
“Ceiling effect”
Buprenorphine-naloxone
Naloxone only becomes bioavailable if the drug is dissolved and injected
intravenously
Effect is not seen when drug is crushed and snorted
Preferred formulation for long term maintenance over buprenorphine alone
Treating Opioid Use Disorder
Buprenorphine-containing medications
Must be prescribed by qualifying physician
Requires “X” DEA number
Michigan currently has 48 physicians treating 30 patients and 5 physicians treating 100 patients
SAMHSA Treatment Locator:
https://www.samhsa.gov/medication-assisted-treatment/physician-program-data/treatment-physician-locator
Treating Opioid Use Disorder
Buprenorphine formulations
Dosing Schedule
Buprenorphine tablet Daily
Buprenorphine implant 6 months
Buprenorphine depot injection Monthly
Buprenorphine/naloxone sublingual tablet Daily
Buprenorphine/naloxone sublingual film Daily
Buprenorphine/naloxone buccal film Daily
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Treating Opioid Use Disorder
Buprenorphine-containing medications
Advantages Disadvantages
Effective Abuse potential
Increased accessibility Requires qualifying physician to
prescribe
Easier to discontinue than
methadone
Naloxone-containing formulations
not recommended in pregnancy
Can precipitate withdrawal early
in treatment
Treating Opioid Use Disorder
Naltrexone
Mechanism
Opioid antagonist competitively blocks reinforcing effects of opioid agonists
Craving reduction psychologically mediated
No prescribing limitations
Also FDA approved in treatment of alcohol dependence
Treating Opioid Use Disorder
Naltrexone
Oral naltrexone
Considered poor choice due to adherence and increased risk of opioid overdose mortality following medication discontinuation
Up regulation in mu-receptors with treatment
Injectable naltrexone
Once monthly intramuscular injection PREFERRED FORMULATION
Treating Opioid Use Disorder
Naltrexone
Advantages Disadvantages
Widely available Adherence with oral tablet
No abuse potential/ opioid-related
adverse effects
Risk of hepatotoxicity
Less stigma Requires at least 7 days of
abstinence before initiation
Improved adherence with
intramuscular injection
Cost with intramuscular injection
Treating Opioid Use Disorder
Opioid-abstinence rates with medication compared to no medication
Medication Percentage opioid free
on medication
Percentage opioid free
on placebo/
detoxification
Naltrexone ER 36 23
Methadone 60 30
Buprenorphine/naloxone 20 to 50 6
Connery HS. Harv Rev Psychiatry.2015;23:63-75.
Treating Opioid Use Disorder-
Patient Cases
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References
Berland D, Rodgers P. Rational use of opioids for management of chronic nonterminal pain. Am Fam Physician 2012;86:252-258.
Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc.2015;90:828-842.
Connery HS. Medication-assisted treatment of opioid use disorder: review of the evidence and future directions. Harv Rev Psychiatry.2015;23:63-75.
Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR Recomm Rep.2016;65(No.1).
Greene MS, Chambers RA. Pseudoaddiction: fact or fiction? An investigation of the medical literature. Curr Addict Rep.2015;2(4):310-317.
Harden P, Ahmed S, Ang K, Wiedemer N. Clinical implications of tapering chronic opioids in a veteran population. Pain Med.2015;16:1975-1981.
Mayo Clinic Medical Laboratories. Benzodiazepines confirmation, urine. Available at: https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/80370. Accessed February 12, 2018.
References
Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83:66-76.
National Institute on Drug Abuse. Principles of Drug Addiction Treatment: A Research-Based Guide (3rd ed). Available at: https://www.drugabuse. gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/preface. Accessed February 10, 2018.
Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med.1980;302:123.
Smith HS. Opioid metabolism. Mayo Clin Proc 2009;84:613-24.
Washington State Agency Medical Directors’ Group. Interagency guideline on opioid dosing for chronic non-cancer pain: an education aid to improve care and safety with opioid therapy (2010 update). Available at: http://www.agencymeddirectors.wa.gov/files/opioidgdline.pdf. Accessed February 7, 2018.