what do you mean the morphine isn’t working?
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What Do You Mean The Morphine Isn’t Working?
Ellen Fulp, PharmD, BCGP
Clinical Education Coordinator
AvaCare, Inc.
Innovation and Excellence in Advanced Illness at End of Life 42nd Annual Hospice & Palliative Care Conference – September 2018 – Charlotte, NC
Objectives
• Discuss the current U.S. opioid epidemic
• Review recommendations for safe prescribing and use of opioid analgesics
• Examine appropriate use of non-opioid analgesics in hospice and palliative care
• Explore patient cases highlighting methadone, high dose opioid infusions, and opioid sparing medications
Innovation and Excellence in Advanced Illness at End of Life The Carolinas Center’s 42nd Annual Hospice & Palliative Care Conference – September 2018 – Charlotte, ,NC
Opioid Epidemic
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Opioid Epidemic
2,100,000People with an opioid use disorder
42,249 People died from opioid overdoses
948,000People used heroin
$504,000,000Economic cost
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Pain Assessment
• NQF #1634 Pain Screening
• Measure Description: Percentage of patient stays during which the patient was screened for pain during the initial nursing assessment.
• NQF #1637 Pain Assessment
• Measure Description: Percentage of patient stays during which the patient screened positive for pain and received a comprehensive assessment of pain within 1 day of the screening.
• location, severity, character, duration, frequency, what relieves or worsens that pain, and the effect on function or quality of life
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Pain Assessment
• Pain Intensity Assessment Tools
• Visual Analogue Scale
• Numeric Rating Scale
• Verbal Descriptor Scale
• FACES Scale (Wong-Baker)
• Faces Pain Scale- Revised
• Pain Thermometer
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Opioid Risk Tool (ORT)
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REMS
• Education– Expectations: goals and quality of life – Opioid Therapy: safe storage, reliable caregiver, tablet
inventory, pain diary, laws– Non-Drug Therapy: relaxation, communication,
support groups
• Treatment Agreement – 4 A’s: Analgesia, Activities, Adverse Effects, Aberrant
Behaviors – PDMP data – Prescriptions: small quantities, ER formulations
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Opioid Prescribing
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Adjuvant Therapy
Acetaminophen
• Mild Pain/Fever• Cost effective formulations:
• Tablets
• Capsules
• Suppositories
• Oral Liquids
Anti-Inflammatory
• NSAIDs• Examples: Ibuprofen,
Naproxen
• Meloxicam, Celecoxib, Diclofenac, Sulindac, Oxaprozin, Piroxicam
• AVOID: Ketorolac, Indomethacin
• Corticosteroids • Examples: Dexamethasone,
Prednisone
• Oral concentrate & Oral elixir
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Adjuvant Therapy
• Antidepressants • Tricyclic Antidepressants (TCA)
• Examples: Amitriptyline, Nortriptyline, Imipramine, Doxepin
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)• Example: Duloxetine
• Anticonvulsants• Examples: Gabapentin, Pregabalin, Carbamazepine,
Oxcarbazepine
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Patient Case: Jessie
• Jessie is a 67 yo female admitted to hospice with primary dx of pancreatic cancer with liver mets
• CC: Lower abdominal pain• Rating 7/10
• Describes as stabbing, aching and constant
• Hx: HTN, Non-smoker, 5’4” 130 lbs
• Current analgesics: • Morphine ER 200mg PO q8h
• Morphine IR 90mg PO q2h prn BTP (using 3 doses/day)
• Total Oral Morphine/day (OME): 870mg
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Opioid Infusions
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Patient Case: Jessie
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Morphine PO 870mg x 1.5mg IV Hydromorphone = 43.5 mg IV Hydromorphone
30mg PO Morphine
43.5 mg IV Hydromorphone x 0.75 (25% reduction) = 32.6 mg IV Hydromorphone
32.6 mg IV Hydromorphone ÷ 24 hours = 1.4 mg IV Hydromorphone/hour
1.4 mg Hydromorphone ÷ 6 = 0.2 mg IV Hydromorphone Q10 minutes PRN breakthrough pain
Hydromorphone IV 1.4mg per hour continuous infusion Hydromorphone 0.2mg IV Q10 minutes PRN breakthrough pain
Patient Case: David
• David is a 49 yo male admitted to hospice with primary dx of cirrhosis
• CC: abdominal pain and distension • Rating 7/10• Describes as dull, aching and constant
• Hx: alcoholism, illicit drug use, 5’9” 160 lbs• Current analgesics:
• Morphine IR 15mg PO q4h prn pain (using 6 doses/day)
• Total Oral Morphine/day (OME): 90mg
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Fentanyl (Transdermal)
• Synthetic opioid • Opioid agonist
• Extra precautions • Potency • Heat exposure (Black Box Warning)
• Prolonged half-life and duration of action • Drug depot effect
• Patch strengths • 12mcg, 25mcg, 50mcg, 75mcg, 100mcg• 37.5mcg, 62.5mcg, 87.5mcg
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Fentanyl (Transdermal)
• Precaution:• Opioid naïve patients • Cachectic patients
• Do NOT increase dose frequently • At least 12 hours to see benefit after patch placement• May take up to 36 hours to reach target blood
concentrations • When patches are removed, about half of the drug is
eliminated from the body after 17 hours • An increase in body temperature can increase
absorption by up to 30%
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Patient Case: David
• Total Oral Morphine/day (OME): 90mg
• 90mg x 0.25% = 22.5mg OME
• 90mg-22.5mg = 67.5mg OME
• 67.5mg OME ÷ 2 = Fentanyl 33.75 mcg/hour
• Fentanyl 25mcg 1 patch changed Q72h
• Oxycodone 10mg PO q6h prn breakthrough pain
• Consider: Diuretic titration
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Patient Case: James
• James is a 60 yo male admitted to hospice with primary dx of prostate cancer
• CC: Lower back and hip pain• Rating 10/10
• Describes as stabbing and burning
• Hx: Diabetes, Non-smoker, 5’7” 145 lbs
• Current analgesics: • Morphine ER 60mg PO q8h• Morphine IR 20mg PO q2h prn BTP (using 5 doses/day)
• Total Oral Morphine/day (OME): 280mg
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Methadone
• Synthetic opioid• Mu-opioid receptor agonist• Inhibits the reuptake of serotonin and norepinephrine• N-methyl-D-aspartate inhibitor
• Bad reputation • 2006 Public Health Advisory
• Long duration of action • Efficacious
• Chronic pain• Neuropathic pain• Refractory pain
• Cost effective
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Dolophine (Methadone) PI. Available at www.fda.gov. Accessed 02/2018.
Methadone
• Most effective opioid for neuropathic pain
• Active N-methyl-D-aspartate (NMDA) receptor antagonist
• Reduces CNS sensitization to pain/hyperalgesia
• Reduces CNS amplification of pain sensation
• Few other known NMDA receptor antagonists:
• Dextromethorphan
• Ketamine
• Memantine
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Methadone
• Routes of Administration • PO, PR, IV, SubQ
• Half-life• Long, but variable (4-130 hours)
• Increases with repeat dosing
• Drug Interactions
• Duration of action• 3-6 hours with INITIATION of dosing
• Increased to 8-24 hours with REPEATED dosing
• Takes 5-7 days to reach steady state
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Methadone
• EKG Monitoring Guidelines • Center for Substance Abuse Treatment Expert Panel
• Ann Intern Med. 2009;150:387-395• U.S. Consensus Guideline
• Palliat Support Care. 2008; 6(2): 165-176.• American Pain Society (APS)
• J Pain. 2014; 15(4):321-337• General Guidelines• Not written specifically for hospice patients
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Methadone
QT Prolongation Risk Factors
• Female
• Impaired liver function
• Arrhythmias, CAD, CHF
• QT prolonging medications – Antipsychotics
– Antiemetics
– Antidepressants
• Electrolyte imbalances
• Methadone > 200mg/day
Approach
• Avoid multiple risk factors
• Arrhythmia is not an absolute contraindication
• Risk vs. benefit conversation
• Monitor for tachycardia, syncope, palpitations, diaphoresis
• Consider baseline EKG with periodic follow-up
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Methadone
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Methadone
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Patient Case: James
• Methadone Equianalgesic dosing ratio• 8:1
• 280mg OME divided by 8 = Methadone 35mg per day
• Dose reduce by 25-50% = 17.5mg to 26 mg• Cross-tolerance
• Recommendation:• Discontinue Morphine ER and Morphine IR 20mg
• Begin Methadone 10mg po q12h and Morphine IR 45mg po q2h prn breakthrough pain
• Consider: Anti-inflammatory
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Patient Case: Lynn
• Lynn is a 45 yo female admitted to hospice with a primary dx of breast cancer
• CC: pain in chest wall and peripheral neuropathy• Rating 7/10• Recently admitted for GIP stay secondary to pain
• Hx/Demo: 2 children at home • Current analgesics:
• Gabapentin 800mg po q8h• Hydromorphone 11mg/hour continuous IV infusion with
3mg IV q15 minutes prn breakthrough pain
• Prognosis is months
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Ketamine
• FDA approved as a general anesthetic• Typically given via the IV or IM route for general anesthesia
induction or maintenance • Mechanism of action: unknown
– N-methyl-D-aspartate (NMDA) receptor antagonist – Additional receptor activity at: nicotinic, muscarinic and
opioid receptors – Preliminary studies and reports suggest additional anti-
inflammatory effects • Produces dissociative analgesia and sedation • Abuse potential
• “Special K”
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Ketamine
• Data is available to support its use in:• Cancer related neuropathic pain
• Reduction in pain intensity
• Cancer pain• Decreased opioid consumption
• Ischemic pain • Significant reduction in pain intensity at 24 hours and 5 days
after initiation
• Complex regional pain syndrome & neuropathic pain etiologies • Reduction in pain intensity; reduction in opioid utilization
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Ketamine
• No studies comparing titration schedules or routes of administration
• Oral Administration • Initial dose: 10-25mg TID to QID
• Titrate by 10-25mg per day
• Maximum dose per day ~200mg
• IV Administration • Initial dose: 50-100mg/day
• Continuous or intermittent infusions
• Titrate by 25-50mg/day
• Usual effective dose ~100-300mg/day
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J Palliat Med 2012; 15(4): 474-483.
Ketamine
• Adverse Effects
• Psychotomimetic: dysphoria, hallucinations, vivid dreams/nightmares, restlessness, psychosis
• Excessive salivation
• Tachycardia
• Newer concerns: neuropsychiatric, urinary and hepatobiliary toxicity
• Common adverse effects at subanesthetic doses: feeling “spaced out”, nausea, sedation, delirium• Pre-medicate: haloperidol or lorazepam
• Caution: known brain mets
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Ketamine
• Patient Counseling
• Report any unusual thoughts or changes in movement
• Take this medication exactly as prescribed
• Store in a safe place and do not share with others
• You may require less of your maintenance pain medications over time• Report feelings of sedation
• Do not stop or start new medications without speaking to your care team
• You should not take ketamine if you have a history of seizures, head trauma, increased blood pressure, or are sensitive to ketamine
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Patient Case: Lynn
• Psychiatric history screening- negative
• Ketamine test dose
• Ketamine 25mg PO TID
• Opioid dose reduction: 50%
• Stop ketamine
• Burst therapy
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Questions
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References
• Anderson, S. L., & Shreve, S. T. (2004). Continuous subcutaneous infusion of opiates at end-of-life. Annals of Pharmacotherapy, 38(6), 1015-1023.
• Berna, C., Kulich, R. J., & Rathmell, J. P. (2015, June). Tapering long-term opioid therapy in chronic noncancer pain: Evidence and recommendations for everyday practice. In Mayo Clinic Proceedings (Vol. 90, No. 6, pp. 828-842).
• AAHPM Methadone Dose Conversion Guidelines.• Chou, R., Cruciani, R. A., Fiellin, D. A., Compton, P., Farrar, J. T., Haigney, M. C., ... &
Mehta, D. (2014). Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. The Journal of Pain, 15(4), 321-337.
• McLean, S., & Twomey, F. (2015). Methods of rotation from another strong opioid to methadone for the management of cancer pain: a systematic review of the available evidence. Journal of pain and symptom management, 50(2), 248-259.
• Covington-East, C. (2017). Hospice-Appropriate Universal Precautions for Opioid Safety. Journal of Hospice & Palliative Nursing, 19(3), 256-260.
• McPherson ML, Demystifying Opioid Conversion Calculations. American Society of Health-System Pharmacists; ©2010.
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References
• Prommer, E. (2012). Ketamine for pain: an update of uses in palliative care. Journal of palliative medicine, 15(4), 474-483.
• Prommer, E. (2016) Fast Fact # 132: Ketamine use in palliative care. Palliative Care Network of Wisconsin.
• Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016;65(No. RR-1):1–49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1
• Webster, L. Opioid Risk Tool. http://www.lynnwebstermd.com/opioid-risk-tool/ . 2018. Accessed August 7, 2018.
• NIH. Overdose Death Rates. https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates . September 2017. Accessed August 7, 2018.
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