Pain management and opioid safety CME grand rounds

December 4, 2014

Optimizing Treatment for Pain Patients and the Opioid Safety

Initiative

V2

Shannon DeGrote, PharmD Amina Ghalyoun, PharmDJaclyn Sievers, PharmD

Objectives

I. Distinguish different types of pain and identify

appropriate first line treatments

II. Manage side effects of opioid use

III. Identify the goals and measures of the opioid

safety initiative

IV. Interpret urine drug screens

V. Recognize recent FDA changes in opioid

scheduling

Epidemiology

“The total number of opioid-related deaths in the United States (>100,000 between 1999 and

2010) far exceeds the number of US military casualties in the Vietnam War (58,000).”

1. Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: Dipiiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.

2. Bohnert AS, Illgen MA, Galea S, McCarthy JF, Blow FC. Accidental Poisoning Mortality Among Patients in the Department of Veterans Affairs Health System Med Care. Apr 2011;49(4):393-3963. Franklin, Gary M, MD. Opioids for Chronic Noncancer Pain. American Academy of Neurology. 2014;83:1277-1284.

Pain“An unpleasant sensory and emotional experience associated with actual or potential tissue damage”

Rosenquist, EWK, MD. Definition and pathogenesis of Chronic Pain. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on November 18, 2014.)

Pathophysiology

Baumann TJ, Strickland JM, Herndon CM. Pain Management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:539-541.

Types of Pain

Description

Somatic • Skin, bone, joint, muscle or connective tissue• Presents with throbbing and well localized

sensation of pain

Visceral • Pain from an internal organ• Feeling of pain from different area other than

location of organ

Neuropathic • Nerve damage • Pain described as burning, tingling, shock like, or

shooting pain


Acute versus Chronic Pain

Acute Pain Chronic Pain

Duration Hours to weeks More than 3 months

Causes Surgery, traumaPain due to a chronic disease or condition

Prognosis Predictable Unpredictable

Complicating Issues UncommonDepression, anxiety,

financial issues

Treatment Primary analgesics Multimodal


Common Examples of Chronic Pain

Osteoarthritis

Neuropathic pain

Fibromyalgia

Somatic pain

OsteoarthritisDamage to protective cartilage in any joint of the body, most commonly hands, knees, hips and spine

• Acetaminophen (APAP)• Non-steroidal anti-inflammatory drugs (NSAIDs)

First line

• Topical & intra-articular analgesics

Second line

• Opioids

Third line

1. Hochberg, Marc C., Roy D. Altman, Karine Toupin April, et al. Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. American College of Rheumatology. 2012;64(4):465-474.

2. Kalunian KC. Initial pharmacologic therapy of osteoarthritis. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

3. Kalunian KC. Treatment of osteoarthritis resistant to initial pharmacologic therapy. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

Neuropathic PainNerve damage in any area of the body, commonly feet and hands, described as tingling or burning pain, weakness and numbness

• Tricyclic antidepressants (TCAs): amitriptyline, nortriptyline• Anti-epileptics (AEDs): gabapentin, pregabalin*• Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs):

venlafaxine, duloxetine*• Central & topical analgesics

First line

• AEDs: carbamazepine, oxcarbazepine, topiramate• Opioids

Second line

1. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2010;17:1113-88.2. National institutte for health and care excellence. NICE clinical guideline 173: neuropathic pain - pharmacological management. Retrieved at: http://www.nice.org.uk/guidance/cg173. Accessed

20 Nov 2014.3. Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.4. Feldman EL, McCulloch DK. Treatment of diabetic neuropathy. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

FibromyalgiaWidespread musculoskeletal pain, believed to be due to amplified pain signals and altered brain processes, accompanied by fatigue, sleep, memory and mood issues.

• Acetaminophen • TCAs: amitriptyline, nortriptyline, desipramine• SNRIs: venlafaxine, duloxetine*, milnacipran*• Cyclobenzaprine

First line

• AEDs: gabapentin, pregabalin*• Selective Serotonin Reuptake Inhibitors (SSRIs): fluoxetine, paroxetine• Tramadol

Second line

• Opioids• NSAIDs

Not recommended

1. Ablin J, Fitzcharles MA, Buskila D, et al. Treatment of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines with special emphasis on complementary and alternative therapies. Evid Based Complement Alternat Med. 2013; 2013:485272

2. Goldenberg DL. Initial treatment of fibromyalgia in adults. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.3. Goldenberg DL.Treatment of fibromyalgia in adults not responsive to initial therapies. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24

2014.

Somatic PainA throbbing, stabbing like pain

• Acetaminophen• NSAIDs

First line

• AEDs: gabapentin, carbamazepine• TCAs: amitriptyline

Second line

• Skeletal muscle relaxants: cyclobenzaprine, benzodiazepines• Opioids for SHORT-TERM use for flare-ups

Third line

1. Walsh, Nicolas E. MD, Peter Brooks, MBBS, J. Mieke Hazes, MD<, PhD, et al. Standards of Care for Acute and Chronic Musculoskeletal Pain: The Bone and Joint Decade (2000-2010). Arch Phys Med Rehabil. 2008;89:1830-1845.

2. Chou R. Subacute and chronic low back pain: pharmacologic and noninterventional treatment. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

3. Anderson BC, Isaac Z, Devine J. Treatment of neck pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.4. Drugs for pain. The Medical Letter. 2013;11:31-42.

Opioids

Chemical Classes of Opioids

Phenanthrenes Phenylpiperidines Diphenylheptanes

Natural Codeine Morphine

Semisynthetic Hydrocodone Hydromorphone Oxycodone Oxymorphone

Synthetic Fentanyl Meperidine

Synthetic Methadone


True Drug Allergy vs Intolerance

“An immune-mediated allergic reaction, usually due to production of antibodies to the medication, that results in hives, wheezing, swelling of the tongue/lips/face and/or anaphylaxis”

Pichler WJ. Drug allergy: classification and clinical features. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

Adverse Drug Reactions

VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.

http://vaww.sites.Irn.va.gov/pain/opioids

Managing Opioid Side Effects

Side Effect Recommendations Tolerance

Constipation• Senna 8.6mg po daily• Docusate 100mg po once or twice daily

NO

Dry mouth• Increase fluid intake• Artificial saliva

Yes

Nausea/vomiting

• Ondansetron 4mg po q8hrs prn• Prochlorperazine 5mg po QID prn

Yes

Pruritus • Diphenhydramine 25mg po q4hrs prn Yes

Sedation• Dose adjustment• Opioid rotation

Yes

Respiratory depression

• Naloxone kits• Avoid polypharmacy (benzodiazepines)

NO

Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.


Identifying High-Risk Patients

Comorbid conditions○ Sleep apnea or sleep disorder diagnosis○ Kidney dysfunction

Concurrent medications○ Benzodiazepines, antihistamines, sedatives or

other CNS depressants Lifestyle choices

○ Smoking, history of alcohol or drug dependence/abuse

Extremes of age



Special Considerations Drug metabolism: liver enzyme (CYP2D6)

polymorphisms Codeine: Black Box Warning

○ Fast metabolizers - more side effects

○ Slow metabolizers/DDIs - less effective

Electrocardiogram changes Methadone: Black Box Warning

○ QTc prolongation



Opioid AnalgesiaWarnings Chronic pulmonary

disease Central sleep apnea

Obstructive sleep apnea

(OSA) not on CPAP

Risk for suicide or

unstable psychiatric

disorder

Receiving treatment for

substance use disorder

(SUD)

Contraindications Severe respiratory

instability

Acute psychiatric

instability

Active diversion and/or

SUD not in remission or

in treatment

Paralytic ileus

True allergy



Risks with Long-Term Use

Changes in sleep architecture

Respiratory depression

Endocrine changes

Immunosuppression

Opioid-induced hyperalgesia

Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.VA/DoD Clinical Practice Guidelines for Management of Opioid Therapy for Chronic Pain. Available at http://vaww.sites.Irn.va.gov/pain/opioids. Accessed 24 Sept 2014.


Treatment of PainNon-pharmacologic

Rosenquist E. Overview of the treatment of chronic pain. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2014. www.uptodate.com. Accessed September 24 2014.

Acupuncture

Chiropractic manipulation

Heat and cold

Massage

Physical therapy

Opioid Safety Initiative

What is it?Action plan to improve patient safety and

quality of pain management specific to opioid therapy

Focus on prescriber education and trainingAligned with national private and public

initiatives to reduce the number of patients on high dose opioids, overdoses, and death

Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014.

Opioid Prescribing Related Changes

Hydrocodone/acetaminophen Schedule II

Tramadol Schedule IV

Naloxone Kits available from FHCC, Departments of Public Health, and retail pharmacies


GoalsIdentify veterans at immediate, short term,

and long term risk of harms associated with high dose opioid therapy

Develop individualized clinical action plan to mitigate risks

Educate opioid prescribers regarding appropriate use and benefits of urine drug screening

Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014


MeasuresUrine toxicology screen in the past yearConcurrent opioid (including tramadol) and

benzodiazepine usersGreater than 400mg morphine (or equivalent)

daily Future: patients on an opioid and with active

SUD not in treatment

Midboe, A. “Patient Safety Center of Inquiry: Promoting Patient Safety through Improved Tools for Opioid Prescribing.” Presentation for Patient Safety Awareness Week. March 06, 2013.Accessed online July 15, 2014

Patient Provider Agreement

Patient-Provider Partnership Agreement. Packard Health A Community Partnership for Care. http://www.packardhealth.org/patient/provideragreement Published 2014. Accessed November 1, 2014.

Urine Drug Monitoring Methods

Enzyme-Multiplied Immunoassay (EMIT)

Gas Chromatography-Mass Spectrometry (GC-MS)

Initial testing Confirmatory testing

Qualitative Quantitative

Contains specific antibodies against drugs and their metabolites

Breaks down drug molecules into ionized fragments and identifies substances based on mass-to-charge ratio

Rapid, inexpensive, widely available Time consuming, expensive

↑ sensitivity, ↓ specificity ↑ sensitivity, ↑ specificity

1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012. 2. Standbridge JB, et al. Am Fam Physician. 2010;81(5):635-640.3. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.

Labs at FHCC Urine Drug Screen (EMIT; Urine Tox Quick Order)

○ Opiates○ Benzodiazepines○ Amphetamines○ Cocaine○ Cannabinoids○ Phencyclidine (PCP)

Results in 24 hours Confirmatory Test (GC-MS)

Automatic send out to Hines VA if EMIT positive for opioids and amphetamines

Results in 48-72 hours

Opioid Metabolism

Oxycodone

Hydrocodone

Codeine Morphine

Hydromorphone

Oxymorphone

CYP2D6

< 15% < 5%

Heroin

6-MAM

1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.

Use and DetectionMarijuanametabolites

Single Use 2-8 days

Chronic Use 20-30 days

Cocaine hours BEG 2-4 days

Opioidmetabolites

Heroin 40 minutes

6-MAM 4-12 hours

Codeine/Morphine2-3 days

Oxycodone 2-4 days

Methadone 3-6 days

AmphetamineAmphetamine

1-2 daysMethamphetamine

3-4 days

BenzodiazepineShort-acting

3 daysLong-acting

30 days

BarbiturateShort-acting

1 dayLong-acting

21 days

Alcohol 7-12 hoursEthyl glucuronide

≥ 72 hours

1. Tenore PL. Journal of Addictive Diseases. 2010;29:436-448.2. Standbridge JB, et al. Am Fam Physician. 2010;81(5):635-640.3. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.4. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.5. Drug Testing: A White Paper of the American Society of Addiction Medicine. 2013.

False Positives Alcohol

OTC cough products Mouth wash

Marijuana Dronabinol Efavirenz PPIs

Cocaine Topical anesthetic

BZD Sertraline ≥ 100mg

Barbiturates Ibuprofen Naproxen

Opioids Poppy seeds Fluoroquinolones Rifampin Verapamil Trazodone

Amphetamines Highly cross reactive with

many medications Amiodarone SSRIs MAOIs TCAs Pseudoephedrine

1. Reisfield GM, et al. Annals of Clinical & Laboratory Science. 2007;37(4):301-314.2. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.3. Tenore PL. of Addictive Diseases. 2010;29:436-448.4. Vincent EC, et al. J Fam Pract. 2006;55(10):893-897. 5. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.6. Brahm NC, et al. Am J Health-Sys Pharm. 2010;67(16):1344-1350. 7. Vincent EC, et al. J Fam Pract. 2006;55(10):893-897.

False Negatives

OpioidsRapid CYP 2D6 metabolizers

BZDsClonazepamLorazepam

HeroinUsually undetectable; short half life6-MAM metabolite detected for 4-6 hours

1. Reisfield GM, et al. Annals of Clinical & Laboratory Science. 2007;37(4):301-314.

2. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;20123. Tenore PL. Journal of Addictive Diseases. 2010;29:436-44.

Frequency of Monitoring

Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain: An educational aid to improve care and safety with opioid therapy 2010 Update.

Limitations of Monitoring Results do not indicate

Length of time exposed to a medication Amounts of a specific drug in the patient’s system Frequency of use True for urine drug screens: use of multiple medications in

the same family Positive results

Reflect use over a few days Do not indicate overall adherence or if the patient is taking

more or less than prescribed. Negative results

Assay not sensitive to the medication a patient is taking Do not indicate lack of use1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.

2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.

Patient Case AD is a 56 year old male with PMH

significant for lumbar spinal stenosis, chronic back pain with sciatica, TIIDM with moderate peripheral neuropathy, and HTN. Pt presents for urine drug test follow up. He’s been managed on the pain regimen below for the past 30 days:Morphine 45mg sustained acting PO BID Morphine 15mg immediate release PO TID PRN Gabapentin 300mg PO TID

UDS Screen

UDS Confirmation

Opioid Metabolism

Oxycodone

Hydrocodone

Codeine Morphine

Hydromorphone

Oxymorphone

CYP2D6

< 15% < 5%

Heroin

6-MAM

1. Gourlay DL, et al. Conneticut: PharmaCom Group, Inc;2012.2. Moeller KE, et al. Mayo Clin Proc. 2008;83(1):66-76.

Patient Case

Pt states he was seen in emergency department for back pain prior to UDS

He was given 1mg hydromorphone (Dilaudid)

Does this explain the (+) hydrocodone?

Questions?

Documents

Pain management and opioid safety CME grand rounds