Opioid Conversions Mixture of Science and Art Matthew J. Pingree, MD Assistant Professor Division of Pain Medicine Physical Medicine and Rehabilitation and Anesthesiology Mayo Clinic, Rochester Pingree.Matthew@Mayo.edu Pain Medicine for the Non-Pain Specialist February 16-18, 2017 2016 MFMER slide-1
Disclosure of Financial Relationships Matthew J. Pingree MD Has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. 2016 MFMER slide-2
Objectives Brief Review of important information regarding some newer opiates Explain the appropriate use of the Equianalgesic Opioid Dosing Chart and limitations Understand the steps to complete and what to consider when changing opioid medication Review some sample cases that highlight important points 2016 MFMER slide-3
Opioid Responsiveness Degree of analgesia achieved as dose escalated Potency Intensity of analgesic effect for a given dose Access to the receptor Binding Affinity Physiochemistry Physical and chemical process of binding to a receptor 2016 MFMER slide-4
Pharmacokinetics What the body does to the drug Absorb Distribute - Metabolize - Excrete Equianalgesic Doses of drug or route that provide the same degree of relief Bioavailaibilty % drug detected in circulation and available to provide relief IV drug = 100% bioavailable! Morphine 30-40% - Hydromorphone 50% Oxycodone 80% - Oxymrophone 10% 2016 MFMER slide-5
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The Equianalgesic Table (Simplified) PO IV/SQ Relative Potency Morphine 30 mg 10 mg 1:3 Oxycodone 20 mg N/A -- Hydromorphone 7.5 mg 1.5 mg 1:5 Fentanyl N/A 100 mcg -- Oxymorphone 10 mg 1 mg 1:10 McPherson, ML. 2010. Demystifying opioid conversion calculations. 2016 MFMER slide-7
Tapentadol MOA Mu receptor agonist, NERI, Weak SSRI Indication Mod - Severe Acute pain >18 years of age Formulation IR 50mg, 75mg, 100mg q 4-6 hours No published data on conversion less potent than morphine (suggested) Tapentadol 50 mg q4-6 -> Oxycodone 5mg Tapentadol 75 mg q4-6 -> Oxycodone 10mg Tapentadol 100 mg q4-6 -> Oxycodone 15mg 2016 MFMER slide-8
Buprenorphine ( ) Brief Facts for Conversions: OME <30 mg/day -> 5 mcg/hr OME >30-80 mg/day - > 10 mcg/hr Potential withdrawal when switching Oral Morphine to TD 1mg:75 mcg Conservative estimate Breakthrough meds should be anticipated. 2016 MFMER slide-9
Extended Release Hydromorphone (Exalgo) Once Daily Moderate to severe chronic pain Not acute pain Only opioid tolerant 3 days to steady state do not change dose IR to LA use equivalent daily dose Breakthrough dose of 10-15% 2016 MFMER slide-10
Abuse Deterrent Formulations DO NOT affect the conversion calculations! reformulated to release all at once Kadian now Core of each bead contains naltrexone Cut crushed or chewed negates effect Currently not available in US IR oxycodone tablet Ingredient causes drug to gel 2016 MFMER slide-11
Careful with the Chart! Source of the Data Single dose in Naïve patients Patient Variability Genetic polymorphism Organ function Age/Sex Unidirectional vs. Bidirectional Morphine to Hydromorphone (5-8:1) not the same as Hydromorphone to Morphine (1:3-4) 2016 MFMER slide-12
Why Change? 1. Lack of response Disease progression Tolerance Adverse effects Combination drug exceeds maximum 2. Development of Adverse Effects (Later w/ Dr. Feely) 1. GI 2. Autonomic (urinary retention..) 3. Cutaneous 4. CNS 5. Allergy 2016 MFMER slide-13
Why Change? 3. Change in Patient Status Cannot Swallow PO to IV 4. Other Cost Availability Beliefs/Prior experience 2016 MFMER slide-14
Extended-release/longacting(ER/LA) opioid: Increased risk of nonfatal overdose. Greatest in the first 2 weeks. ER/LA opioids found no clear differences related to pain or function Special Communication CDC Guideline for Prescribing Opioids for Chronic Pain United States, 2016 Deborah Dowell, MD, MPH; Tamara M. Haegerich, PhD; Roger Chou, MD 2016 MFMER slide-15
Recommendation about Selection, Dosage, Follow-Up and Discontinuation 1. Immediate-release opioids to initiate therapy 2. Start with the lowest effective dosage 3. For acute pain, use for least amount of time 3 days or less and not usually more than 7 days. 4. Evaluate benefits and harms in 1 to 4 weeks. Special Communication CDC Guideline for Prescribing Opioids for Chronic Pain United States, 2016 Deborah Dowell, MD, MPH; Tamara M. Haegerich, PhD; Roger Chou, MD 2016 MFMER slide-16
5 Steps of Opioid Conversion 1. Assess the patient (PQRSTU) 2. Determine Total Daily Dose 3. Decide on new agent Consult Equianalgesic Table 4. Individualize dosage based on current situation 5. Follow-up and reassessment 2016 MFMER slide-17
5 Steps of Opioid Conversion 1. Assess the patient (PQRSTU) Precipitating and Palliating Breakthrough analgesics? Quality stabbing, shooting Region and Radiation deep/superficial Severity Best and worst Temporal constant, come/go U how is it affecting YOU- sleep, appetite. 2016 MFMER slide-18
5 Steps of Opioid Conversion 2. Total Daily Dosage (TDD) Complete list and how the patient is actually taking the medicine Long and short acting included Opportunities for patient education Remember all routes of administration 3. Decide on new medication Can they swallow? Renal function Type of pain Availability Drug interactions Calculate new dose 2016 MFMER slide-19
5 Steps of Opioid Conversion 1. Calculate the current daily dose 2. Set up conversion ratio of current opioid to new opioid X mg new opioid/route x equivalent dose new opioid/route mg current opioid/route equivalent dose current opioid/route X mg hydromorphone/po x 7.5 mg Hydromorphone/PO 90 mg morphine/po 30 mg morphine /PO (X)(30) =(90)(7.5) (X) = 22.5 mg hydromorphone/po per day 2016 MFMER slide-20
5 Steps of Opioid Conversion 4. Individualize to the patient Decrease Adverse effects Incomplete cross-tolerance Same Pain not controlled Increase Severe pain or crisis Route: Home alone? Hospitalized? SNF? Dosing Frequency Account for residual medicine during transition Trust your gut! 2016 MFMER slide-21
5 Steps of Opioid Conversion 5. Monitoring the patient Pain rating Sleep? More functional? Adverse effects Sedation Pupils Respiratory rate Cognition 2016 MFMER slide-22
Case #1 JP 62 yo M with Multiple Myeloma and diffuse bony metastasis Morphine ER 30 BID Morphine IR Liquid 10 mg every 2 hours Using about 5x s Senna Dexamethasone 4 mg BID Temazapam 15 mg QHS Lorazapam 1 mg PO Q4 Pain is 5-7/10 not controlled 2016 MFMER slide-23
Case #1 JP 62 yo M with Multiple Myeloma and diffuse bony metastasis Step 1 - Assess Anxious, fearful, Deep/aching, Continuous with acute worsening Step 2 TDD 30 mg ER Tabs BID x 2 = 60 mg 10 mg IR Liquid 5 x = 50 mg TDD = 110 mg morphine per day 2016 MFMER slide-24
Case #1 Step 3 Calculate starting dose of IV Morphine TDD x 10 mg IV/30 mg PO = TDD New 110 x 1/3 = 36.7 mg = TDD IV Morphine Step 4 Individualize Increase dose due to poor control No cross tolerance 25-50% increase appropriate 0.25 x 36.7 = 9.175 mg increase 9.175 + 36.7 = 45.875 mg new TDD Q4 hour dosing = 45.875/ 6 doses = 7.64 2016 MFMER slide-25
Case #1 7.5 mg IV Morphine Q4 hours When do you give the first IV dose? Last dose of LA 7 hours ago Last dose of IR 3 hours Pain is increasing IV dose NOW! 2016 MFMER slide-26
Case #1 Step 5: Monitor and Follow-up Reassess 20-60 minutes IV morphine 5 minutes onset 15-20 minutes peak 12-24 hours to steady state No relief 25-50% increase 10 mg Q 4 hours 2016 MFMER slide-27
Case #2 DT 62 yo F recent bowel surgery. 12mg IV Hydromorphone/24 hours Good pain control what to go home on? Step1: TDD = 12 mg ID Hydromorphone Step 2: Equivalent dose 12 mg IV x 7.5 mg PO/1.5 mg IV = 60 mg PO Hydromorphone per day 60 mg PO Hydromorphone 20 mg Oxycodone/7.5 Hydromorphone = 160 mg Oxycodone per day 2016 MFMER slide-28
Case #2 Pain is currently well controlled and expected to decrease 25-50% reduction 80-120 TDD Option #1 15-20 mg Q4 = 90-120 mg IR Option #2 40 mg BID ER, 5-10 mg IR Q4 =110-140 mg Cross tolerance? 2016 MFMER slide-29
Case #3 TC 45 yo M with lung cancer pain has been increasing over the past several weeks Percocet 10/325 6 tablets/day Continuous increasing pain. Not well controlled. Lost his insurance - Morphine. Step 2: TDD = 60 mg Oxycodone 2016 MFMER slide-30
Case #3 60 mg Oxycodone x 30 Morphine/20 Oxycodone = 90 mg Morphine Pain is not controlled 25-50% increase New TDD with increase = 60 mg Morphine ER 30 mg BID 15 mg IR Oxycodone Q4 hours PRN 2016 MFMER slide-31
Case #4 KG 52 yo woman with chronic pain and significant nausea with oral pain medication Current: TDF 25 mcg/h 20 mg PO BID Hydromorphone 4 mg Q4h 6/day Calculate TDD (w/o TDF): 40 mg Oxycodone x 30 mg Morphine/20 mg Oxycodone = 60 mg PO morphine 24 mg Hydromorphone x 30 mg morphine/7.5 mg hydromorphone = 96 mg Morphine TDD (w/o TDF) = 156 mg OME 2016 MFMER slide-32
Converting to TDF 1. Determine OME 2. Use conversion of 2:1 (mg oral morphine per DAY to mcg/hr) 3. Round up or down based on: Patch Strength Pain Level Overall Clinical Status 156 OME x 1 mcg Hr TD Fentanyl/2 mg OME Day = 78 mcg/hr --> 75 mcg patch 25 mcg/hr TD Patch + 75 mcg/hr TD patch = 100 mcg/hr TD patch Beitbart W.,et al., Oncology, 2000 2016 MFMER slide-33
Case #4 How do we implement our plan? Option 1: Place 100 mcg patch at time of last Dose 100 mcg/hr = 200 mg OME/day 10-15% for breakthrough = 20-30 mg mg PR Option 2: Place 100 mcg patch at time of last Dose 200 OME x 7.5 mg Hydromorphone/30 Morphine = 50 mg PO Hydromorphone 50 mg PO Hydromorphone x 1.5 IV/7.5 PO = 10 mg IV Hydromorphone/Day 1-1.5 mg IV Hydromorphone q 4 hours 2016 MFMER slide-34
Case #4 Timing information Add 75 mcg now or take off 25 mcg and replace with 100 mcg/hr patch 12 hours to see clinically meaningful increase At least 36 hours to achieve maximum steady state 2016 MFMER slide-35
Transdermal Fentanyl Common Mistakes: Acute pain Intermittent or mild pain Not opioid tolerant Following for >1 week 60 morphine 25 mcg/hr TDF 30 mg Oxycodone 8 mg hydromorphone 25 mg oxymorphone 17 hours after removal 50% Fentanyl is eliminated from body 2016 MFMER slide-36
Fentanyl Rapid Acting All for opioid tolerant Cancer Pain Start with lowest dose and titrate Fentanyl lozenge Buccal Tablet (Fentora) Buccal soluble film (Onsolis) Sublingual tablet (Abstral) Nasal Spray (Lazanda) 2016 MFMER slide-37
Drug Conversion Conclusions 1. Be aware and alert as to when clinical scenario may dictate a change 2. Understand Principles associated with changing (responsiveness, potency, etc.) 3. Use five step conversion process 4. Use a fair and balanced equianalgesic dosing chart understand limitations 5. Consider the timing of the switch 6. Document and educate 2016 MFMER slide-38
Mayo Clinic Locations 2016 MFMER slide-39
Questions & Discussion 2016 MFMER slide-40