OPIOID MANAGEMENT and REMS PRINCIPLES: WHAT WOULD YOU DO?

1. OPIOID MANAGEMENT and REMS PRINCIPLES:WHAT WOULD YOU DO? • JAMES W. ATCHISON, DO (MODERATOR) • MEDICAL DIRECTOR • RIC CENTER FOR PAIN MANAGEMENT

2. DISTINGUISHED PANEL • STEVEN STANOS, DO • SWEDISH MEDICAL CENTER, SEATTLE, WA • BRIAN BRUEHL, MD • MD ANDERSON, HOUSTON, TX • MICHAEL BRENNAN, MD • PAIN CENTER OF FAIRFIELD, FAIRFIELD, CT • R. NORMAN HARDEN, MD • ANALGESIC RESEARCH CONSULTANTS, ATHENS, GA

3. DISCLOSURES • JAMES W. ATCHISON, DO • SITE INVESTIGATOR, PFIZER/PARAXEL STUDY OF PREGABALIN FOR TRAUMATIC NERUOPATHIC PAIN • MEDICAL REVIEW ACTIVTY – BEST DOSCTORS, INSPE • STEVEN STANOS, DO • VERBAL DISCLOSURE • MICHAEL BRENNAN, MD • SPEAKER/CONSULTANT • PURDUE, TEVA, DEPOMED, ASTRZENECA, PERNIX, IROKO, KALEO, CAVA • PRIOR STOCKHOLDER • CAVA

4. DISCLOSURES • BRIAN BRUEHL, MD • CONSULTANT FOR MEDTRONIC NEUROMODULATION, SPINE AND RESTORATIVE THERAPIES • CONSULTANT FOR BOSTON SCIENTIFIC NEUROMODULATION • UNRESTRICTED RESEARCH SUPPORT FROM JAZZ PHARMACEUTICALS • SITE PRIMARY INVESTIGATOR, JAZZ PHARMACEUTICALS (PRIZM STUDY) • R. NORMAN HARDEN, MD • NO DISCLOSURES

5. LEARNING OBJECTIVES • Participants will be able to: • Direct patient education according to reference guidelines regarding safe prescribing, storage, and dose adjustments of opioids. • Utilize concepts of rational polyp pharmacy in chronic pain management. • Evaluate and recommend appropriate adjunct of treatments beyond medications for chronic pain management

6. REMS BLUEPRINT REVIEW • MAJOR HEADINGS • Why Prescriber Education is Important • I. Assessing Patients for Treatment with ER/LA Opioid Analgesic Therapy • II. Initiating Therapy, Modifying Dosing, and Discontinuing Use of ER/LA Opioid Analgesics • III. Managing Therapy with ER/LA Opioid Analgesics presentation

7. REMS BLUEPRINT REVIEW • MAJOR HEADINGS • IV. Counseling Patients and Caregivers about the Safe Use of ER/LA Opioid Analgesics • V. General Drug Information ER/LA Opioid Analgesic Products • VI. Specific Drug Information presentation

8. CASE PRESENTATION • 48 y/o F presents for Tx w/ Hx of chronic Rt UL pain. S/P Fx of Radius & Ulna 2 y/a after fall. Pain level 5-8/10 ; referred due to completion of all w/u & Tx from ortho. Increased pain w/ all movements of arm and restricted use. Left knee pain w/ walking and standing tolerance of 25 minutes. Works as Administrative Assistant. Current Rx for Hydrocodone 5/325 to be used 1-2 q 4-6 hours as needed, and now taking 8 tabs per day. All records available for review. presentation

9. WHAT WOULD YOU DO? PROCESSES BEFORE RX INITIAL RX? 1. Hydrocodone 5/325 up to 4/day 2. Hydrocodone 10/325 up to 4/day 3. Rotate to other Short Acting opioid 4. Transition to Long Acting opioid 5. No Rx on 1st visit • Hx/visit includes Risk Stratification • Review possible risks & side effects • Review Patient Counseling Document • Review/sign Patient Agreement • Complete UDS presentation

10. RISK STRATIFICATION presentation

11. WHAT WOULD YOU DO? COMMONLY USED TOOLS WHICH IS BEST? • ORT • SOAPP-R • PSYCOLOGY INTERVIEW • COMM presentation

12. REVIEW & SIGN PATIENT AGREEMENT presentation

13. OPIOID ANALGESICS • PATIENT AGREEMENTS • OPIOID THERAPY UTILIZED ONLY AFTER ALL OTHER REASONABLE ATTEMPTS HAVE FAILED • SINGLE PHYSICIAN PRESCRIBER & PHARMACY • PT MUST AGREE TO COGNITIVE-BEHAVIORAL TX • PRESCRIPTIONS MUST LAST UNTIL THE NEXT VISIT • BRING IN ALL UNUSED MEDICATIONS

14. OPIOID ANALGESICS • PATIENT AGREEMENT • PT MUST INFORM DOCTOR OF ALL OTHER MEDICATIONS AND CHANGES • NO BENZOS OR CARISOPRODOL • ? PREGABLIN • PT MUST AGREE TO RANDOM URINE TESTING • INFORM PATIENT OF ALL RISKS (LIST) • INCLUDING TOLERANCE, DEPENDANCE, ADDICTION • SIDE EFFECTS

15. OPIOID ANALGESICS • PATIENT AGREEMENT • ANY EVIDENCE OF DRUG HOARDING, DRUG DIVERSION, UNAGREED-UPON DOSE CHANGES, LOSS OF RX, OR FAILURE TO FOLLOW THE AGREEMENT WILL (MAY?) RESULT IN TAPERING OF MEDICINE AND DISCONTINUATION OF DOCTOR-PATIENT RELATIONSHIP • DESIGNED TO LIMIT DIVERSION

16. WHAT WOULD YOU DO? DO YOU REGULARLY USE THESE? YES NO presentation

17. REVIEW RISKS AND SIDE EFFECTS OF OPIOIDS presentation

18. Clinical Effects of Opioids Desirable effects Analgesia Relief of Anxiety Undesirable effects Nausea/vomiting Urinary Retention Mental Status Changes Respiratory Depression Tolerance / Dry Mouth / Drug Dependence Circumstantial effects Sedation Euphoria Cough Suppression Decreased Bowel Motility Mycek, et al., eds. Pharmacology, 2d ed. Philadelphia; Lippincott-Raven, 1997.

19. Opioid Adverse Effects Usually dose related and some are drug specific Common Constipation Dry mouth Nausea/Vomiting Sedation Sweating Less Common Respiratory depression Bad dreams/hallucinations Dysphoria/delirium Myoclonus/seizures Arrhythmia Pruritis/urticaria Urinary retention Amenorrhea/sexual dysfunction presentation

20. Anticipate/Manage Side Effects Respiratory Depression - Sedation precedes respiratory depression Role of sedation scales? - Respiratory rate alone is not an indication of respiratory function. - Use Naloxone sparingly Respiratory depression reverses before analgesia Limit to doses of 100 micrograms at a time One amp (0.4mg) in 4ml NS Inject 1 ml at a time- can always give more. presentation

21. WHAT WOULD YOU DO? UPDATED HISTORY OPTIONS Add Colace, Sennakot, Miralax, etc, daily Start Provigil in am & noon Use compazine PRN Use Albuteral inhaler PRN Start Clonazepam at HS? Repeat UDS • Continues Hydrocodone at 10/325 QID • She experiences: • Constipation • Sleepiness in the afternoon • Occasional nausea • Occasional SOB • She is not sleeping well at night presentation

22. REVIEW OF PATIENT COUNSELING DOCUMENT presentation

23. Patient Counseling Document (PCD) • The DOs and DON’Ts of Extended-Release / Long - Acting Opioid Analgesics • DO: •  Read the Medication Guide •  Take your medicine exactly as prescribed •  Store your medicine away from children and in a safe place •  Flush unused medicine down the toilet •  Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

24. Patient Counseling Document (PCD) • DON’T: Do not give your medicine to others Do not take medicine unless it was prescribed for you Do not stop taking your medicine without talking to your healthcare provider Do not break, chew, crush, dissolve, or inject your medicine. If you cannot swallow your medicine whole, talk to your healthcare provider. Do not drink alcohol while taking this medicine • For additional information go to: dailymed.nlm.nih.gov

25. Secure prescriptions the same way as other valuables in the home, like jewelry or cash • Take prescription medications out of the medicine cabinet and hide them in a place only you know about • Encourage relatives and friends to secure their medications • If possible, keep all medicines in a safe place • An existing fire safe or gun safe • Use a cut-proof bag designed for travel safety • Locking medicine box or cabinet Safe Storage of Opioids Secure Monitor • Patients should always be in a position to know if any pills are missing • Take note of how many pills are in each prescription bottle or pill packet • Keep track of your refills for your own medication, as well as for other members of the household • Make sure friends and relatives— especially grandparents—are aware of the risks and regularly monitor their own medicines APF. PainSAFE™. Problems with Opioids Can Be Prevented. Available at: http://www.painfoundation.org/painsafe/healthcare-professionals/pharmacotherapy/opioids/preventing-problems.html. Accessed February 3, 2012. 45

26. OPIOID SAFETY • STORAGE OF MEDICATIONS • LIMIT NUMBER OF PERSONS THAT ARE AWARE YOU ARE USING PAIN MEDS • BE AWARE OF OTHER PATIENTS OR PERSONS AROUND PHYSICIAN’S OFFICE • BE AWARE OF PERSONS WATCHING AT PHARMACY • LIMIT DISCUSSIONS WITH FAMILY AND FRIENDS • KEEP MEDS AWAY FROM FAMILY MEMBERS • DO NOT ASK THEM TO GET MEDICATIONS FROM STORAGE

27. OPIOID SAFETY • DATA FROM 2009-2010 National Survey on Drug Use and Health • 70% of the 2.4 million Americans who abuse prescription drugs for the first time each year get them from friends and family • 1/3 are teenagers

28. OPIOID SAFETY • DATA FROM 2009-2010 National Survey on Drug Use and Health • Casual Abusers of Rx Drugs(< 1x/wk) • 55% got substances FREE from friends/family • 11% PURCHASED substance from friends or family • 5% TOOK WITHOUT PERMISSION substances from family/friends

29. OPIOID SAFETY • DATA FROM 2009-2010 National Survey on Drug Use and Health • Chronic Users/Abusers of Rx Drugs(> 1x/wk for more than a year) • 41% got substances WITH OR WITHOUT PERMISSION from friends/family • 25% PURCHASED substance from dealer or the internet • 25% OBTAINED THEM FROM A DOCTOR

30. WHAT WOULD YOU DO? UPDATED HISTORY OPTIONS Manage this over the phone until next visit Review Patient Agreement and DC from the clinic Review pharmacy issues Review storage issues Repeat UDS? • After 4 months, she calls into clinic for early refill as she is out of her pills and is not sure why? presentation

31. UDS MONITORING presentation

32. WHAT WOULD YOU DO? UDS RESULTS OPTIONS Repeat the test w/ Inc sensitivity – continue Tx Counsel pt and repeat at next visit – continue Tx Counsel pt and DC from clinic Give 1 month Rx? Counsel pt and Refer to Addiction Medicine Give 1 month Rx? • No Substances present? • Hydrocodone and Hydromorphone present • w/ Oxymorphone • w/ benzodiazepine • w/ ETOH • w/ THC • w/ Cocaine • w/ Morphine, codeine, and oxycodone presentation

33. Choosing Opioid Therapy • Chronic pain management should be individualized • Selection of a specific opioid based on criteria: efficacy, tolerability, safety, and ease of use. • Initiated at a low dose and gradually increase- monitor pain reduction and side effects. • Patients must be fully informed about the nature of their treatment, benefits and harmful effects • Long acting versus breakthrough doses

34. WHAT WOULD YOU DO? ADDITIONAL HISTORY OPTIONS 1. Increase Hydrocodone to 6-8 tabs/day 2. Rotate to other SA Opioid 3. Initiate LA/ER Opioid 4. Test UDS & Continue current Hydrocodone 5. Stop the medication 6. Refer to Addiction Medicine 7. Further Work-up? • Received Rx for Hydrocodone 10/325 QID for 6 months (compliant!). • She previously split some pills in ½, but is now receiving less response to whole pills. Pain 7-9/10 • Having a difficulty time working. presentation

35. ROTATING SA THERAPY presentation

36. WHAT WOULD YOU DO? SA OPTIONS OPTIONS Taper the Hydrocodone, then start new med Stop Hydrocodone; start new med at lower MEQ Stop Hydrocodone; start new med at same MEQ Stop Hydrocodone; start new med at Inc MEQ • Oxycodone • w/ Aceteminophen? • Hydromorphone • Morphine Sulphate • Oxymorphone • Tapentadol • How many MEQ? presentation

37. DEPENDENCE IS NOT ADDICTION • Physical dependence: • “Physical dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.”

38. DEPENDENCE IS NOT ADDICTION • Addiction: • “Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. • It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.”

39. OPIOID ANALGESICS • TOLERANCE • NEED FOR INCREASING AMOUNT OF THE DRUG TO ACHIEVE THE SAME EFFECT DUE TO THE PROGRESSIVE LOSS OF EFFECTIVENESS OF THE DRUG WITH ALL OTHER CONDITIONS CONSTANT

40. INITIATING LA THERAPY presentation

41. WHAT WOULD YOU DO? LA OPTIONS OPTIONS Taper the Hydrocodone, then start new med Stop Hydrocodone; start new med at lower MEQ Stop Hydrocodone; start new med at same MEQ Stop Hydrocodone; start new med at Inc MEQ Start new med and use Hydrocodone for BTP • Oxycontin • MSContin/Oramorph/ MSER/Avinza • Duragesic, Fentanyl Patch • Opana ER • Exalgo • Nucynta ER • Dolphine, Methadone • Butrans Patch • Zohydro ER, Hysingla ER presentation

42. WHAT WOULD YOU DO? INFLUENCES START/DON’T START MS Contin Fentanyl Avinza Oxycontin Opana ER Nucynta ER Methadone Butrans Zohydro ER • Dosage Issues • Insurance coverage • Side Effects/History • Current Medications • Social History • REMS rules presentation

43. INITIATING THERAPY OF ER/LA OPIOIDS • According to Blueprint - may be used for initial dosing in non-tolerant pts. • Avinza 30 mg daily • Butrans patch 5 mcg/hr every 7 days • Dolophine 2.5-10 mg every 8-12 hours • Embeda 20 mg/0.8 mg every 12-24 hours • Nucynta ER 50 mg every 12 hours • Opana ER 5 mg every 12 hours • Oxycontin 10 mg every 12 hours

44. INITIATING THERAPY OF ER/LA OPIOIDS • According to Blueprint - should not be used for initial dosing in non-tolerant pt • Duragesic patch • Exalgo • Kadian • MS Contin (?) • Require a calculation of dose from current use • Based on conversion tables? • There are increasing concerns with this!

45. INITIATING THERAPY OF ER/LA OPIOIDS • According to Blueprint - Initial titration interval: • (minimum number of days before it can be changed again) • Oxycontin – 1-2 days • Kadian – 2 days • MS Contin – 2 days • Opana ER – 2 days • Avinza – 3 days

46. INITIATING THERAPY OF ER/LA OPIOIDS • According to Blueprint - Initial titration interval: • (minimum number of days before it can be changed again) • Butrans – 3 days • Embeda – 3 days • Nucynta ER – 3 days • Duragesic – 72 hours • Exalgo – 3-4 days • Dolophine – Not reported – should be 7 days or more

47. MODIFYING DOSING OF ER/LA OPIOIDS • Titrate increase in ER/LA opioid medication on regular intervals • 25-33% changes for 1-2 visits • 10-20% for continuing visits • Eventually titrate SA opioid to return to only PRN use

48. MODIFYING DOSING OF ER/LA OPIOIDS • Stop further titration of ER/LA opioid when: • Adequate analgesic effects • Unacceptable side effects • No increase in analgesic response for 1 – 2 changes • Ceiling levels • Avinza, Butrans, Nucynta, ?Dolphine

49. SIGNS/SYMPTOMS OF ONSETRESPIRATORY DEPRESSION • Any Trouble Breathing • Hypopnea or apnea • Cannot be easily aroused • Intoxicated behavior – confusion, slurred speech, stumbling • Unusual snoring, gasping, or snorting (especially with sleep) • Fingertips/lips are blue/purple

50. SIGNS/SYMPTOMS OF ONSETRESPIRATORY DEPRESSION • Recent Review Article in NEJM • Edward Boyer, MD, PhD N Engl J Med 2012; 367; 146-155 • Internet Education/Assistance • Opioids911.org • Many Others