KHCHA Annual Meeting 9/20/18 - Workshop H2 Transitions in Life Managing Pain When it Matters Most Michael F Dandurand PharmD, BCGP, FACA Objective ● Intro to pain ● Assessment ● Principles of pain control ● Opioid analgesics 1 Pain ● Occurs 70% of patients with cancer ● Occurs 65% of patients with non- malignant disease Definition ● “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”- International Association for the Study of Pain' ● Whatever the patient says it is! 2 Types of Pain ● Nociceptive o Specific pain receptors are stimulated o Includes somatic and visceral ● Neuropathic o No specific receptors stimulated o AKA nerve pain o Burning and electrical feel Pain Tolerance Lowered by: ● Discomfort ● Boredom ● Insomnia ● Sadness ● Fatigue ● Depression ● Anxiety ● Introversion ● Fear ● Social abandonment ● Anger ● Mental isolation 3 Pain Tolerance Raised by: ● Relief of symptoms ● Sleep ● Elevation of mood ● Rest or physiotherapy ● Finding meaning and ● Relaxation therapy significance ● Explanation/support ● Social inclusion ● Understanding/empathy ● Support to express ● Diversion emotions Pain Assessment ● Patient is central to pain assessment ● Diagnose the cause of pain ● Take detailed history of the pain ● Use patient self-assessment 4 Pain Scales healthonecares.com Regular monitoring with: queri.research.va.gov ● Visual analogues scales ● Numerical scales ● Wong-Baker Faces Pain Scale WHO Analgesic Ladder Step 1 (pain less than 3/10) Step 2 (pain 3-6/10) Step 3 (pain over 6/10) ntnu.edu 5 WHO Analgesic Ladder ● Start at step according to pain severity ● Choose drug based pain severity, not disease stage ● Use strong opioids when steps 1 and 2 analgesics fail ● Choose analgesic of different potency if pain relief failed ● Treat moderate-to-severe pain with opioid analgesics Adjuvant Analgesics Adjuvant analgesics can be added at any stage Drugs Indication NSAID ● Bone pain ● Soft tissue infiltration ● Hepatomegaly Corticosteroids ● Raised intracranial pressure ● Soft tissue infiltration ● Nerve compression ● Hepatomegaly ●Bone Pain Antidepressants and Anticonvulsants ● Nerve compression or infiltration ● Paraneoplastic neuropathies Ketamine (special use only) ● Refractory pain ●Neuropathic pain ● Ischaemic limb pain 6 Pain Management Principles ● Goal: patients pain free at rest and during activity ● Analgesics scheduled, not PRN in continuous pain ● Pain is easier to prevent than relieve ● Additional pain medication prior to activity ● Simplest regimen, least drugs used, appropriate form, and interval ● Ensure treatment goals regularly ● Provide patient information about treatment ● Encourage patient involvement 1st-line Treatment Recommendations ● Oral sustained-release morphine for maintenance in patients requiring strong opiates ● Transdermal patches not for first line ● If patient’s pain cannot be controlled with first line therapy after optimization, revise treatment 7 1st-line Treatment for Breakthrough Pain ● Offer immediate-release morphine, if tolerable ● Fentanyl not for first-line rescue medication timeinc.net 1st-line Treatment Recommendations: Transdermal When oral option is intolerable ● Transdermal Options: Fentanyl and Buprenorphine ● Use lowest cost transdermal patches ● Initiate after patient’s pain stabilize, due to long titration period ● Convert opiate doses with caution 8 1st line Recommendations: Subcutaneous When oral opioids are not tolerable: ● Use subcutaneous opioids with the lowest cost Sample Options: ● Morphine ● Hydromorphone ● Fentanyl Opioids Potency Effect of Opioid Receptors Weak Opioids Pure agonists Partial Agonist Codeine Morphine Buprenorphine Meperidine HYdromorphone Oxymorphone Oxycodone Fentanyl Methadone Strong Opioids Agonist-antagonist Pure Antagonists Morphine Pentazocine Naloxone Hydromorphone Nalbuphine Naltrexone Oxymorphone Butorphanol Methylnaltrexone Oxycodone Fentanyl Methadone 9 Codeine ● Mild-to-moderate pain treatment ● Weak affinity for opioid receptor ● About 10 percent metabolized to morphine ● Available as single and in combination with acetaminophen or aspirin ● Also indicated as antitussive Tramadol ● Binds weakly to opioid receptors, inhibit uptake of serotonin and norepinephrine, and promotes serotonin release ● Caution with other serotonin uptake inhibitors ● Available as combination with acetaminophen or single agent as immediate or long-acting 10 Hydrocodone ● Similar structure to codeine ● Weakly binds to opioid receptor ● Moderate-to-severe pain ● Commercially available as combination Meperidine ● Synthetic opioid ● Less potent, shorter duration of action than morphine ● Seizure risk ● Not for long term, elderly, or renally impaired patients 11 Morphine ● Backbone of first-line therapy ● Standard of opioid comparison ● Moderate-to-severe pain ● Available in multiple formulations Misconceptions of Morphine Explained Patients normally believe: ● It is very addictive ● Respiratory depression issue ● Significant tolerance develops ● Morphine is stupefying 12 Recommendations for Starting Morphine ● Initiate 4-hourly doses of normal-release morphine tablets or elixir ● Allow extra doses for “breakthrough pain” PRN ● After 24 hours, total the day’s intake and divide by 6 to get the dose for every 4 hours. ● Regular starting dose for 4-hourly is 5-10 mg morphine Maintenance dose of Morphine ● After pain stabilized, use sustained release preparations ● Breakthrough pain not associated with unusual acvity should be treated with morphine at ⅙ total daily dose 13 Oxycodone ● 25-50% more potent than morphine ● Oral only ● Available in combinations with acetaminophen, ibuprofen, and aspirin ● Immediate and long-acting available Hydromorphone ● Semisynthetic derivative of morphine ● 7-11 times more potent than morphine ● Oral and parenteral 14 Oxymorphone ● Active metabolite of oxycodone ● More potent than oxycodone ● 10 times more potent than morphine ● Oral and parenteral available ● Immediate and long-acting available Methadone ● Synthetic opioid receptor agonist, NMDA receptor blocker, serotonin and norepinephrine reuptake inhibitor ● Long half-life (8-59 hours) ● Opioid withdrawal treatment ● Has effect on neuropathic pain ● Effective for acute pain, but used primarily for chronic cancer and noncancer pain 15 Dosing Methadone: Opioid Naive Patient Gradual Titration Initiation ● 2.5 mg every 8 hours ● Slowly titrate to effect Faster Titration Initiation ● 2.5 mg every 6-8 hours ● Slowly titrate to effect ● These recommendations represent a conservative approach Methadone Conversion Table Daily Oral Morphine Dose Ratio Estimated Methadone <100 mg 3:1 20-30% 100-300 mg 5:1 10-20% 300-600 mg 10:1 8-12% 600-1,000 mg 12:1 5-10% >1,000 mg 20:1 5% 16 Methadone Conversion Example 1 ● Oral morphine dose: 80 mg daily ● Calculated Methadone dose: 15 mg daily 80*20%=16 mg ● Initial Methadone dose: 5 mg q8h 15 mg/3=5 mg ● Increase by calculated MET dose every 5-7 days PRN Example 2 ● Oral morphine dose: 300 mg daily ● Calculated methadone: 30 mg daily 300*10%=30 mg ● Initiate methadone dose: 10 mg q8h 30 mg/3=10 mg ● Increase by calculated MET dose every 5-7 days PRN 17 Daily Oral Morphine Exceeding 500 mg Example 3 ● For morphine doses greater than 500 mg daily; add a third of the calculated methadone dose every 5 days Example: ● Oral morphine dose: 600 mg daily ● Calculated methadone: 42 mg daily 600*7%=42 mg methadone ● 1st 5 days: 5 mg methadone q8h and 400 mg morphine (in divided doses) (⅓)*42=14 mg, next closest dose is 15 mg, 15/3=5 mg q8h, 600 mg*(⅔)=400 mg ● Next 5 days: 10 mg methadone q8h, 200 mg morphine (in divided doses) 42*(⅔)=28, next closest dose is 30 mg, 30/3=10 mg q8h, 600*(⅓)=200 mg ● Then 15 mg methadone q8h, no morphine Changing Methadone Dosing Interval ● Determine daily dosage for adequate analgesia ● Trial of longer dosing intervals may be attempted ● When patients are stable, divide total daily dose into every 12 hours 18 Buprenorphine Transdermal Patch ● Opioid partial agonist and antagonist ● Ceiling analgesia and respiratory depression ● Drug half-life is 30 hours ● Can displace pure agonist such as morphine and induce withdrawal Buprenorphine Conversion ● Available as Butrans 5, 7.5, 10, 15, and 20 mcg/hour Patch Strength Morphine Equivalent Butrans 5 mcg Oral Morphine less than 30 mg/ 24 hours Butrans 10 mcg Oral Morphine 30 mg-80 mg/ 24 hours Butrans may not be Oral Morphine over 80 mg/24 hours appropriate for pain relief, use alternate analgesic Manufacturer Recommendations 19 Starting Buprenorphine ● Opioid naive: 5 mcg/hr patch, titrate up as necessary ● Previously on opioid: Find equivalent converted dose ● Begin weekly with breakthrough pain meds PRN ● Dose adjustments: recommend after 7 days; not more frequently than 3 days ● Maximum dose: 20 mcg/hr patch ● Doses ≥40 mcg/hr may be associated with QT prolongation Fentanyl ● Synthetic opioid ● 100 times more potent than morphine ● Transdermal patch for moderate-severe pain ● Transmucosal(lozenge, sublingual) for breakthrough pain 20 Fentanyl Transdermal Patch ● Onset 6-12 hours ● Steady state achieved after 3-6 days ● Change patch every 72 hours Fentanyl Conversion Methods FDA Manufacturing Label Breitbart Method ● The manufacturer recommendation is a ● Brietbart recommended ratio of 2:1 very conservative approach and often ● 2 mg oral morphine/24 hr = 1 mcg/hr undertreats pain of transdermal fentanyl ● Example: Patient on 145 mg oral morphine/day would use a 75 mcg/hr fentanyl patch ● Brietbart