Opioid Pain Management. John Manfredonia, DO. Disclosures. Dr. Manfredonia discloses his employment as Regional Medical Director for VistaCare

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Opioid Pain Management John Manfredonia, DO Disclosures Dr. Manfredonia discloses his employment as Regional Medical Director for VistaCare VistaCare has provided commercial support for this activity Palliative medicine frequently involves the use of medications for off-label purposes. Such use may be discussed during this presentation.

Objectives Discuss the types of pain Describe the assessment of pain Describe how to select an opioid medication, including appropriate & effective use of various delivery routes Discuss the management of opioid side effects the alleviation of suffering is the warrant of medicine and its test of adequacy it is a test that contemporary medicine fails despite the brilliance of its science and its awesome technological power. -Eric J. Cassell

GUIDELINES Assess the Pain Select the appropriate analgesic. Prescribe the appropriate dose. Administer by the appropriate route. Schedule the appropriate dosing interval. GUIDELINES..continued Prevent persistent pain and relieve incidental or breakthrough pain. Prevent, anticipate, and manage the side effects of the drug. Use appropriate adjuvant drugs.

When left untreated, pain can cause a patient s emotional and spiritual death long before the actual end of life. Cancer patients in pain: Turk, Monarch, Williams TYPES OF PAIN NOCICEPTIVE NEUROPATHIC INTRACRANIAL SOMATIC VISCERAL

SOMATIC Etiology tissue damage / inflammation Symptoms Aching / Throbbing / Localized Source Bone / Skin / Joints / Muscle Examples Bone Mets / Fractures / Arthritis / Cellulitis VISCERAL PAIN Etiology Tumor Involvement infiltration/compression Obstruction Symptoms Colicky / Cramping / Intermittent Vomiting / Constipation Poorly localized / Referred Source Organs

VISCERAL PAIN obstruction Cause Occlusion of Lumen Lack Of propulsion Etiology Constipation opioids Colon / Ovarian Cancer Lung Ogilvie NEUROPATHIC Etiology Compression / Infiltration / Injury Radiation / Chemo Therapy Symptoms Excruciating / Lancinating / Burning Paroxysmal / Intermittent Source Myelopathy / Plexopathy / Radicuopathy Trigeminal Neuralgia / Herpes Zoster

INTRACRANIAL Etiology 25% Tumor Compression / Infiltration / Hemorrhage Increased Pressure / Edema Symptoms Cephalgia / Focal Weakness / Mental Changes Seizures / Ataxia / Aphasia Source Primary Brain Metastasis Lung / Melanoma / Breast Assessment of Pain Intensity Source Barriers Types of Formulations Routes of Administration Dosing / Titration Response to Medication SELECTION OF MEDICATION

ASSESSING PAIN PAIN SCALE MILD 1-3 MODERATE 4-7 SEVERE 8-10 Scales

Commonly Used Opioids Drugs Oxycodone Morphine Hydromorphone Fentanyl Methadone Short-Acting OxyIR 5,15,30mg 20mg/mL concentrate MSIR 10,15,30mg 10 & 20mg/5mL soln 20mg/mL concentrate Dilaudid 2,4,8mg,5-10 mg/5ml liq, 3mg supp Actiq 200, 400, etc. Long-Acting OxyContin 10, 20, 40, 80 mg MSContin 15,30,60, 100,200mg Kadian 20,30,50,60,100mg Palladone 12,16,24,32mg Duragesic 25,50,75, 100ugm Methadose 5,10,40mg + liquid Morphine Route Onset (minutes) Peak (minutes) Duration (hours) Titration (minutes) IV 5-10 15-30 3-4 10 SC 10-20 30-60 3-4 10-20 PO 30-60 60-90 3-4 120

CONVERSIONS Morphine PO : SQ 3 : 1 Hydromorphone PO : SQ 5 : 1 Morphine to Hydromorphone PO : PO 4 : 1 PO : SQ 20 : 1 SQ : SQ 4-7 : 1 Fentanyl to Morphine 2x Patch Strength = 24hr Morphine Dose Actiq : 200mcg = 6mg Morphine po THE MAXIMUM DOSE OF AN OPIOID? THERE IS NONE!!!

Oral Rectal Stomal Parenteral Subcutaneous Intravenous Transdermal Epidural / Intrathecal ROUTES OF ADMINISTRATION ORAL Advantages Preferred Route Simple / Non-invasive / Flexibility of Dosing Convenient / Highly Effective / Inexpensive Administration Tablet / Liquid / Crushed Short Acting / Long Acting Sublingual

ORAL Disadvantages Slow Onset of Action Delayed Peak Time Dependent on Patient / Caregiver Compliance Ability to Swallow GI Absorption First Pass Effect RECTAL Advantages Alternative to Oral Dosing Nausea / Vomiting / Dysphagia Alternative to Parenteral No Conversion Necessary Emergency Situations

RECTAL Disadvantages Objectionable to Patient / Family Inconvenience Delayed Onset of Action Local Discomfort Limited Dosage Range / Absorption Spontaneous Expulsion Presence of Feces TRANSDERMAL Advantages Convenient 48-72 hour duration Less Constipation Allergy to Morphine / Hydromorphone Disadvantages Variable Absorption / Skin Irritation Not Suitable for Rapid Titration (12-16 hours) Caution with Asian patients

PARENTERAL ANALGESIA Morphine First Drug of Choice Onset 5-20 minutes Titration 10-20 minutes Conversion PO to SQ..3:1 Parenteral Concentration 10mg/ml to 50mg/ml Range of Daily Dose Average 400-600mg 10%..>2000mg Rare.20,000mg Hydromorphone Alternative to Morphine Onset same as morphine Titration Conversion PO to SQ...5:1 Oral Morphine..20:1 SQ Morphine 4-7:1 Parenteral Concentration 5mg/ml to 100mg/ml PARENTERAL Subcutaneous & Intravenous Indications / Advantages Oral / Rectal Route Unavailable Rapid Effect 100% Bioavailability Continuous Infusion Disadvantages Greater Expense then Oral Route Caregiver / Family must Master Technique

SUBCUTANEOUS Advantages Onset of Action...10-20 minutes Greater & Easier Mobility then IV site Duration of Site = 1 week Disadvantages 4 ml / hr limit Localized Pain INTRAVENOUS Advantages Rapid Onset of Action 5-10 minutes Peak Effect 15-30 minutes Rapid Titration every 10 minutes Disadvantage Venous Availability Less Mobility Greater Expense

BREAKTHROUGH/INCIDENTAL PAIN Breakthrough pain is defined as that transient increase in pain that rises to a moderate/severe intensity when the baseline pain is well controlled. Episodic worsening of pain from physical or emotional stressors. Provide rescue doses on these occasions. Ideally, no more than 2 or 3 rescue doses per day. BREAKTHROUGH PAIN rescue Provide 10-15% of total 24-hour oral dose every 1-2 hours as needed for pain. Provide 25-50% of the hourly parental dose ( IV / SQ ) every 15-30 minutes

DOSE ADJUSTMENTS Gradual Escalation until Adequate Pain Control or Intolerable Side-effects When Switching Medication Decrease by 50-75% with Good Pain Control Decrease by 0-25% with Inadequate Control Methadone reduce by 25% Parenteral no change necessary ESCALATING PAIN Disease Progression Increase in Psychological Stressors Non-compliance by Patient or Caregiver Assure Appropriate and Timely Delivery Inappropriate Route of Delivery Tolerance to Medication

SIDE EFFECTS RESPIRATORY DEPRESSION SEDATION CONFUSION CONSTIPATION NAUSEA PRURITIS / RASH URINARY RETENTION Opioid-Induced Neurotoxicity High Dose / Prolonged Use Renal Insufficiency Excitation Delirium / Agitation / Myoclonus / Hallucinations / Seizures / Hyperalgesia Sedation / Coma Treatment Hydration / Dose Reduction / Opioid Rotation

RESPIRATORY DEPRESSION Sedation precedes respiratory depression No patient has succumbed to (opioid induced) respiratory depression while awake Monitor for reduction of normal respirations Caution with Opioid Naïve Patients ADVERSE REACTIONS Determine Compliance Assure Appropriate and Timely Delivery Individual Variability Side Effects Reduce Dosage Switch to Alternative Opioid Adjuvant Medication Opioid Dependence.Withdraw

Medication Cost Professional Pharmacy (5-02-05) Equivalent Dose Palladone 48mg q d OxyContin 80mg q 12h Duragesic 100ug/h MSContin 100mg q 12h Methadone 10mg q 12h Methadone Liq 10mg/ml Cost per month $1,100 $753 $644 $356 $24 $120 CASE PRESENTATIONS

Case 1 46 yo male with head & neck cancer, s/p radical dissection. Present medication includes: 1. Duragesic Patch 100ugm x 3 q 72 hours 2. Oxycontin 20mg 3 q 12 hours 3. Percocet 5/325 (2) q 4 hours 4. MSIR 20mg q2 hours (12 doses in 24 hrs) 5. Ativan and Flexeril. Patient rates his pain >8/10. Your approach to pain control in this patient would be? Options 1. Continue present regiment and increase until adequate pain control is achieved 2. Convert to one long acting and one short acting medication and adjust accordingly 3. D/C all oral/transdermal medication and convert to parenteral administration.

Determine total daily dosage Morphine Equianalgesic Equivalent Dose Duragesic 300ug/qd 600mg Oxycontin 20mg iii bid...120mg Percocet 5 ii q4h 40mg MSIR 20mg q2h..240mg Total...1000mg/qd Convert to Parenteral Morphine Total daily dosage is 1000 mg, therefore the parenteral dose would be? The hourly dose would be? The adjusted hourly dose would be? The rescue dose and frequency would be?

Convert to Parenteral Morphine Total daily dosage is 1000 mg, therefore the parenteral dose would be 333mg The hourly dose would be 14mg The adjusted hourly dose would be 10mg The rescue dose and frequency would be 2.5mg every 15 minutes Case 2 Mrs. W. has metastatic ovarian cancer. She is presently taking 200mg of sustained release oral morphine every 12 hours. She can no longer swallow her medication. Her pain is adequately controlled. The following dose and route of administration would be a reasonable alternative. A. Duragesic 100ugm/hr two patches q 72 hours B. The same dose and frequency of MS Contin per rectum C. Change to MSIR 20mg/ml, 1.75ml q 2 hours po D. Methadone Liquid 10mg/ml, 2ml(20mg) q 12 hours E. Change to subcutaneous morphine 5mg/hr via continuous infusion pump.

Case 2 A. Duragesic 100ugm/hr two patches q 72 hours B. The same dose and frequency of MS Contin per rectum C. Change to MSIR 20mg/ml, 1.75ml q 2 hours po D. Methadone Liquid 10mg/ml, 2ml(20mg) q 12 hours E. Change to subcutaneous morphine 5mg/hr via continuous infusion pump. All of the above are considerations Case 3 67 yo male with Rectal Cancer metastatic to bladder and spine. S/P surgical resection with radiotherapy and surgical spinal decompression x 2. Co-morbidities of COPD. Hx of DVT. Location: Home Caregiver: Spouse (daughter deceased from over-dose of Oxycontin) PPS: 40% Ht: 69 Wt: 136 lbs BMI 20 Pain: 4-6/10 Neuropathic lower extremities

Medication Duragesic Patch 150ugm q 72 h Oxycontin 20mg q 12 h Endocet 7.5mg (1-2) q 4 h Nortriptyline 10mg (2) po at hs Coumadin 2mg po qd Klonopin 1mg po hs Recently D/C: Megace, Decadron, Reglan, Zofran, Macrodantin, Vancomycin (6wks IV) Your approach to pain control in this patient would be?

Morphine Equivalent Duragesic 150ugm/hr = 300mg Oxycontin 20mg bid = 40mg Endocet 7.5mg = 60mg? Total = 400mg Day 1 D/C Duragesic / Oxycontin / Endocet Start: Methadone 10mg q 8 h po Day 5 Roxicodone 50mg/ml 40mg q 2 h Methadone 20mg q 8 h Roxicodone 60mg q 2 h Day 8 d/c oral meds and change to PCA Morphine 16mg/hr continuous iv with 4mg q 15 minutes prn Day 9 MS 24mg/hr prn

Day 11 MS 50mg/hr Day 12 MS 90mg/hr Day 15 MS 160mg/hr Day 16 develop tolerable myoclonus discontinue morphine Change to: Hydromorphone 36mg/hr with 9mg every 15 minutes prn Day 18 Dilaudid 45mg/hr Day 20 Dilaudid 90mg/hr Day 21 develops myoclonus/hallucinations Dilaudid 70mg/hr Add: Methadone 10mg q 8 h po Depakote 250mg Day 22 hallucinations resolved Dilaudid 60mg/hr Methadone 20mg q 8 h Day 23 Dilaudid 40mg/hr Methadone 40mg q 8 h Depokate 250 mg bid

Day 33 Dies comfortably at home QUESTIONS?