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


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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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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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.


drug screen?

Drug Result

Benzodiazepines

Alpha-OH-alprazolam Not detected

Alprazolam Detected

Opiates

Methadone Detected

EDDP Not detected


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).


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.


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?


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



Fentanyl 75 mcg/hour Morphine ER 180 mg/day


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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


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.


Clonidine

Opioid withdrawal is largely due to overactivity of noradrenergic system

Alpha-2 agonists activate presynaptic alpha-2 receptors, reducing sympathetic

activity


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


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


Methadone

Advantages Disadvantages

Requires daily trip to receive dose

Effective More respiratory depression and

sedation than buprenorphine

Safe in pregnancy QT prolongation/ drug interactions


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


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


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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Buprenorphine-containing medications


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


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


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


Naltrexone


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


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.

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