Presentation on theme: "Presented by CO*RE Collaboration for REMS Education"— Presentation transcript:
1Presented by CO*RE Collaboration for REMS Education www.corerems.org Achieving Safe Use While Improving Patient CarePresented by CO*RECollaboration for REMS EducationPresented by CO*RECollaboration for REMS EducationCollaborative forREMS Education
2Faculty Information Daniel G. Williams, DO Assistant Professor of Osteopathic Manipulative MedicineMarian University College of Osteopathic MedicineBoard Certified: Neuromusculoskeletal Medicine and Osteopathic ManipulationDISCLOSURE:Dr. Williams has nothing to disclose.
3Collaborative for REMS Education On July 9, 2012, the Food and Drug Administration (FDA) approved a Risk Evaluation and Mitigation Strategy (REMS) for extended-release (ER) and long-acting (LA) opioid medications.Founded in June, 2010, the Collaborative on REMS Education (CO*RE), a multidisciplinary team of 10 partners and 3 cooperating organizations, has designed a core curriculum based on needs assessment, practice gaps, clinical competencies, and learner self-assessment to meet the requirements of the FDA REMS Blueprint.
5Products Covered by this REMS Brand Name ProductsGeneric ProductsAvinza® morphine sulfate ER capsulesButrans® buprenorphine transdermal systemDolophine® methadone hydrochloride tabletsDuragesic® fentanyl transdermal system*Embeda® morphine sulfate/naltrexone ER capsulesExalgo® hydromorphone hydrochloride ER tabletsKadian® morphine sulfate ER capsulesMethadoseTM methadone hydrochloride tabletsMS Contin® morphine sulfate CR tabletsNucynta® ER tapentadol ER tabletsOpana® ER oxymorphone hydrochloride ER tabletsOxyContin® oxycodone hydrochloride CR tablets†Palladone® hydromorphone hydrochloride ER capsulesFentanyl ER transdermal systemsMethadone hydrochloride tabletsMethadone hydrochloride oral concentrateMethadone hydrochloride oral solutionMorphine sulfate ER tabletsMorphine sulfate ER capsulesOxycodone hydrochloride ER tablets* Not currently available due to voluntary recall (still approved); † No longer marketed (still approved)
7Opioids Should Balance: Prescribers of ER/LAOpioids Should Balance:The benefits ofprescribingER/LA opioids totreat painThe risks ofserious adverseoutcomes
8Opioid Misuse/Abuse is a Major Public Health Problem Improper use of any opioid can result in serious AEs including overdose & deathThis risk can be greater w/ ER/LA opioidsER opioid dosage units contain more opioid than IR formulationsMethadone is a potent opioid with a long, highly variable half-lifeIn 2011,In 2010,34.2 million Americans age ≥12 had used an opioid for nonmedical use some time in their life425,247 ED visits involved nonmedical use of opioidsMethadone involved in 30% of prescription opioid deathsSAMHSA. (2012). Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-44, HHS Publication No. (SMA) Rockville, MD. SAMHSA. (2012). The DAWN Report: Highlights of the 2010 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. Rockville, MD. CDC. CDC Vital Signs. Prescription Painkiller Overdoses. Use and abuse of methadone as a painkiller FDA. Questions and Answers: FDA approves a Risk Evaluation and Mitigation Strategy for Extended-Release and Long-Acting Opioid Analgesics
9Kochanek KD, et al. National Vital Statistics Report 2011;60:1-117 Kochanek KD, et al. National Vital Statistics Report 2011;60: CDC Vital Signs. Prescription Painkiller Overdoses. Use and abuse of methadone as a painkiller Warner M, et al. Drug poisoning deaths in the United States, NCHS data brief, no 81. Hyattsville, MD: National Center for Health Statistics National Center for Injury Prevention and Control. Division of Unintentional Injury Prevention. Policy Impact. Prescription Painkiller Overdoses. Nov 2011.
11Learning ObjectivesDescribe appropriate patient assessment for treatment with ER/LA opioid analgesics, evaluating risks and potential benefits of ER/LA therapy, as well as possible misuse. Apply proper methods to initiate therapy, modify dose, and discontinue use of ER/LA opioid analgesics, applying best practices including accurate dosing and conversion techniques, as well as appropriate discontinuation strategies. Demonstrate accurate knowledge about how to manage ongoing therapy with ER/LA opioid analgesics and properly use evidence-based tools while assessing for adverse effects. Employ methods to counsel patients and caregivers about the safe use of ER/LA opioid analgesics, including proper storage and disposal. Review/assess general and product-specific drug information concerning ER/LA opioid analgesics and identifying potential adverse effects of ER/LA opioids.
12Unit 1THIS IS WHERE WE WILL FIND AN IMAGE – humanize, add warmth, etc – FOR EACH UNIT INTRO
13Balance Risks Against Potential Benefits Conduct thorough H&P and appropriate testingComprehensive benefit- to-harm evaluationBenefits IncludeRisks IncludeAnalgesia (adequate pain control)Improved FunctionOverdose: ER/LA dosage units contain more opioid than IR drugsAbuse by patient or household contactsMisuse & addictionPhysical dependence & toleranceInteractions w/ other medications & substancesInadvertent exposure by household contacts, especially childrenGet outside records as part of the H&PChou R, et al. J Pain. 2009;10: Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. Modified Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM pdf
15Clinical Interview: Patient Medical History Illness relevant to (1) effects or (2) metabolism of opioidsPulmonary disease, constipation, nausea, cognitive impairmentHepatic, renal diseaseIllness possibly linked to substance abuse; eg:HepatitisHIVTuberculosisCellulitisSTIsTrauma, burnsCardiac diseasePulmonary diseaseChou R, et al. J Pain. 2009;10: Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain
16Clinical Interview: Pain & Treatment History Description of painLocationIntensityOnset/DurationVariations/Patterns/RhythmsQualityWhat relieves the pain?What relieves the pain?What causes or increases pain?Effects of pain on physical, emotional, and psychosocial functionPatient’s pain & functional goalsHeapy A, Kerns RD. Psychological and Behavioral Assessment. In: Raj's Practical Management of Pain. 4th ed. 2008; Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010.
17Clinical Interview: Pain & Treatment History, cont’d Pain MedicationsPast useCurrent useQuery state PDMP where available to confirm patient reportContact past providers & obtain prior medical recordsConduct UDTDosageFor opioids currently prescribed: opioid, dose, regimen, & durationImportant to determine if patient is opioid tolerantGeneral effectivenessNonpharmacologic strategies & effectiveness
18Perform Thorough Evaluation & Assessment of Pain Seek objective confirmatory dataComponents of patient evaluation for painOrder diagnostic tests (appropriate to complaint)Order diagnostic tests (appropriate to complaint)General: vital signs, appearance, posture, gait, & pain behaviorsMusculoskeletal ExamInspectionPalpationPercussionAuscultationProvocative maneuversCutaneous or trophic findingsNeurologic examLalani I, Argoff CE. History and Physical Examination of the Pain Patient. In: Raj's Practical Management of Pain. 4th ed. 2008; Chou R, et al. J Pain. 2009;10:
19Assess Risk of Abuse, Including Substance Use & Psychiatric Hx Obtain a complete Hx of current & past substance usePrescription drugsIllegal substancesAlcohol & tobaccoSubstance abuse Hx does not prohibit treatment w/ ER/LA opioids but may require additional monitoring & expert consultation/referralFamily Hx of substance abuse & psychiatric disordersHx of sexual abuseSocial history also relevantEmployment, cultural background, social network, marital history, legal history, & other behavioral patterns
20Risk Assessment, cont’d Be knowledgeable about risk factors for opioid abuseUnderstand & use addiction or abuse screening toolsConduct a UDTPersonal or family Hx of alcohol or drug abuseYounger agePresence of psychiatric conditionsAssess potential risks associated w/ chronic opioid therapyManage patients using ER/LA opioids based on risk assessmentUnderstand limitations
21Risk Assessment Tools: Examples # of itemsAdministeredPatients considered for long-term opioid therapy:ORT Opioid Risk Tool5By patientSOAPP® Screener & Opioid Assessment for Patients w/ Pain24, 14, & 5DIRE Diagnosis, Intractability, Risk, & Efficacy Score7By clinicianCharacterize misuse once opioid treatments begins:PMQ Pain Medication Questionnaire26COMM Current Opioid Misuse Measure17PDUQ Prescription Drug Use Questionnaire40Not specific to pain populations:CAGE-AID Cut Down, Annoyed, Guilty, Eye-Opener Tool, Adjusted to Include Drugs4RAFFT Relax, Alone, Friends, Family, TroubleDAST Drug Abuse Screening Test28SBIRT Screening, Brief Intervention, & Referral to TreatmentVaries
22Prior to opioid therapy Opioid Risk Tool (ORT)Mark each box that appliesFemaleMale1.Family Hx of substance abuseAlcoholIllegal drugsPrescription drugs2.Personal Hx of substance abuse3.Age between 16 & 45 yrs4.Hx of preadolescent sexual abuse5.Psychologic diseaseADD, OCD, bipolar, schizophreniaDepressionAdminister13On initial visitPrior to opioid therapy23443344Scoring (risk)550-3: low4-7: moderate≥8: highIt is commonly believed that risk is uniform across age groups, but this is not so.1132211Webster LR, Webster RM. Pain Med. 2005;6:Scoring Totals:
23Screener & Opioid Assessment for Patients with Pain (SOAPP)® Identifies patients as at high, moderate, or low risk for misuse of opioids prescribed for chronic painHow is SOAPP® administered?Usually self-administered in waiting room, exam room, or prior to an office visitMay be completed as part of an interview w/ a nurse, physician, or psychologistPrescribers should have a completed & scored SOAPP® while making opioid treatment decisionsSOAPP® Monitoring Recommendations. https://painedu.org/soapp/SOAPP_Monitoring_Recommendations.pdf The SOAPP® Version 1.0 Tutorial. https://painedu.org/soapp-tutorial_01.asp
24When to Consider a Trial of an Opioid Pain is moderate to severeFailed to adequately respond to nonopioid & nondrug interventionsContinuous, around-the-clock opioid analgesic is needed for an extended period of timePotential benefits are likely to outweigh risksConsider referral to pain or addiction specialist for patients where risks outweigh benefitsNo alternative therapy is likely to pose as favorable a balance of benefits to harmsChou R, et al. J Pain. 2009;10: Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic PainCollaborative for REMS Education
25When to Consider a Trial of an Opioid, cont’d 60-yr-old w/ chronic disabling OA painNonopioid therapies not effective, IR opioids provided some relief but experienced end-of-dose failureNo psychiatric/medical comorbidity or personal/family drug abuse HxHigh potential benefits relative to potential risksCould prescribe opioids to this patient in most settings w/ routine monitoring30-yr-old w/ fibromyalgia & recent IV drug abuseHigh potential risks relative to benefits (opioid therapy not 1st line for fibromyalgia)Requires intensive structure, monitoring, & management by clinician w/ expertise in both addiction & painNot a good candidate for opioid therapyChou R, et al. J Pain. 2009;10:
26When to Consider a Trial of an Opioid, cont’d Selection of patients between these 2 extremes requires:Careful assessment & characterization of patient riskStructuring of care to match riskIn patients w/ Hx of substance abuse or a psychiatric comorbidity, this may require assistance from experts in managing pain, addiction, or other mental health concernsIn some cases opioids may not be appropriate or should be deferred until the comorbidity has been adequately addressedConsider referralChou R, et al. J Pain. 2009;10:
27Referring High-Risk Patients Prescribers shouldUnderstand when to appropriately refer high-risk patients to pain management or addiction specialistsAlso check your state regulations for requirementsChou R, et al. J Pain. 2009;10:Collaborative for REMS Education
28Special Considerations: Elderly Patients Does patient have medical problems that increase risk of opioid-related AEs?Respiratory depression more likely in elderly, cachectic, or debilitated patientsAltered PK due to poor fat stores, muscle wasting, or altered clearanceMonitor closely, particularly whenInitiating & titrating ER/LA opioidsGiven concomitantly w/ other drugs that depress respirationReduce starting dose to 1/3 to 1/2 the usual dosage in debilitated, non-opioid-tolerant patientsTitrate dose cautiouslyOlder adults more likely to develop constipationRoutinely initiate a bowel regimen before it developsIs patient/caregiver likely to manage opioid therapy responsibly?American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57: Chou R, et al. J Pain. 2009;10:Collaborative for REMS Education
29Special Considerations: Children For pediatric patients, <18 years:Safety & effectiveness of most ER/LA opioids* unestablishedPediatric analgesic trials pose challengesMost opioid studies focus on inpatient safetyOpioids are common sources of drug errorOpioid indications are primarily life-limiting conditionsFew children with chronic pain due to non-life-limiting conditions should receive opioidsExtra information about adolescent and young adult ER/LA opioid use:- Younger than 25 years old, put in moderate risk category in the least. (Goulay, et al., 2005)Pediatric demographic variables related to nonmedical use of opioids:- Female 2 times more likely to abuse than males- Race: White, non white Hispanic, mixed race, Native American/Alaskan- Education: School drop outs, no plans for college- Perceived poor to fair health, hospitalized in past year, 3 or more ED visits in past year- Weekly nonmedical opioid use, history of major depressive episode, disordered alcohol use in past year are characteristics common to prescription opioid abuse and dependence. (Frese & Eiden, 2011)References: Frese, W. A., & Eiden, K. (2011). Opioids: Nonmedical use and abuse in older children. Pediatrics in Review, 32, e44Ye52. Gourlay, D. L., Heit, H. A., & Almahrezi, A. (2005). Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Medicine, 6, 107Y112.When prescribing opioids to children:Consult pediatric palliative care team or pediatric pain specialistor refer to a specialized multidisciplinary pain clinic* Transdermal fentanyl approved in children aged ≥2 yrsBerde CB, et al. Pediatrics. 2012;129: Gregoire MC, et al. Pain Res Manag 2013;18:47-50.Mc Donnell C. Pain Res Manag. 2011;16: Slater ME, et al. Pain Med. 2010;11:
31Initiating TreatmentPrescribers should regard initial treatment as a therapeutic trialMay last from several weeks to several monthsDecision to proceed w/ long-term treatment should be intentional & based on careful consideration of outcomes during the trialProgress toward meeting therapeutic goalsPresence of opioid- related AEsChanges in underlying pain conditionChanges in psychiatric or medical comorbiditiesIdentification of aberrant drug-related behavior, addiction, or diversionChou R, et al. J Pain. 2009;10:113-30
32ER/LA Opioid-Induced Respiratory Depression Chief hazard of opioid agonists, including ER/LA opioidsIf not immediately recognized & treated, may lead to respiratory arrest & deathGreatest risk: initiation of therapy or after dose increaseManifested by reduced urge to breathe & decreased respiration rateShallow breathingCO2 retention can exacerbate opioid sedating effectsInstruct patients/family members to call 911*Managed w/ close observation, supportive measures, & opioid antagonists, depending on patient’s clinical statusBreathing patterns known as “Cheyne-Stokes respiration” – snoring, gasping, groggy, drowsy, shallow breathingChou R, et al. J Pain. 2009;10: FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics InformationforPatientsandProviders/UCM pdf
33ER/LA Opioid-Induced Respiratory Depression More likely to occurReduce riskIn elderly, cachectic, or debilitated patientsContraindicated in patients w/ respiratory depression or conditions that increase riskIf given concomitantly w/ other drugs that depress respirationProper dosing & titration are essentialDo not overestimate dose when converting dosage from another opioid productCan result in fatal overdose w/ first doseInstruct patients to swallow tablets/capsules wholeDose from cut, crushed, dissolved, or chewed tablets/capsules may be fatal, particularly in opioid-naïve individualsFDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
34Initiating & Titrating: Opioid-Naïve Patients Drug & dose selection is criticalSome ER/LA opioids or dosage forms are only recommended for opioid-tolerant patientsCheck individual drug PIMonitor patients closely for respiratory depressionEspecially within h of initiating therapy & increasing dosageIndividualize dosage by titration based on efficacy, tolerability, & presence of AEsCheck ER/LA opioid product PI for minimum titration intervalsSupplement w/ IR analgesics (opioids & nonopioid) if pain is not controlled during titrationThe ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression Chou R, et al. J Pain. 2009;10: FDA. Blueprint for Prescriber Education for ER/LA Opioid Analgesics InformationforPatientsandProviders/UCM pdf
35Initiating: Opioid-Tolerant Patients If opioid tolerant—no restrictions on which products can be usedPatients considered opioid tolerant are taking at least60 mg oral morphine/day25 mcg transdermal fentanyl/hr30 mg oral oxycodone/day8 mg oral hydromorphone/day25 mg oral oxymorphone/dayAn equianalgesic dose of another opioidStill requires caution when rotating a patient on an IR opioid to a different ER/LA opioidThe ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression
36Opioid Rotation Definition: Change from an existing opioid regimen to another opioid w/ the goal of improving therapeutic outcomes or to avoid AEs attributed to the existing drug, e.g., myoclonusRationale:Differences in pharmacologic or other effects make it likely that a switch will improve outcomesEffectiveness & AEs of different mu opioids vary among patientsPatients show incomplete cross-tolerance to new opioidPatient tolerant to 1st opioid can have improved analgesia from 2nd opioid at a dose lower than calculated from an EDTReasons for rotation: Poor opioid responsiveness: Dose titration yields intolerable/unmanageable AEs, Poor analgesic efficacy despite dose titration, Patient desire or need to try a new formulation, Cost or insurance issues, Adherence issues, Concern about abuse or diversion, Change in clinical status requires an opioid w/ different PKProblematic drug-drug interactionsFine PG, et al. J Pain Symptom Manage. 2009;38: Knotkova H, et al. J Pain Symptom Manage. 2009;38: Pasternak GW. Neuropharmacol. 2004;47(suppl 1):
37Relative potency estimates Equianalgesic DosesOpioid rotation requires calculation of an approximate equianalgesic doseEquianalgesic dose is a construct derived from relative opioid potency estimatesRelative potency estimatesPotency refers to dose required to produce a given effectRatio of doses necessary to obtain roughly equivalent effectsCalculate across drugs or routes of administrationRelative analgesic potency is converted into an equianalgesic dose by applying the dose ratio to a standard
38Equianalgesic Dose Tables (EDT) Many different versions:PublishedOnlineOnline InteractiveSmart-phone appsVary in terms of:Equianalgesic valuesWhether ranges are usedWhich opioids are includedMay or may not include transdermal opioids, rapid-onset fentanyl, ER/LA opioids, or opioid agonist-antagonists
39Example of an EDT Drug Oral Parenteral Conversion ratio to oral morphineMorphine30 mg10 mgParenteral morphine: 3 times as potent as oral morphineOxycodone20 mgNAOral oxycodone: ~1.5 times as potent as oral morphineHydrocodoneOral hydrocodone: ~1.5 times as potent as oral morphineHydromorphone7.5 mg1.5 mgOral hydromorphone: ~4-7 times as potent as oral morphineParenteral hydromorphone: 20 times as potent as oral morphineFentanyl15 mcg/hrTransdermal fentanyl: ~80 times as potent as morphine (based on studies converting from morphine to fentanyl)Emphasize the relative potency of hydromorphone ER.
40Limitations of EDTsSingle-dose potency studies using a specific route, conducted in patients w/ limited opioid exposureDid Not ConsiderChronic dosingHigh opioid dosesOther routesDifferent pain typesComorbidities or organ dysfunctionGender, ethnicity, advanced age, or concomitant medicationsEmphasis on limitation of UDT, non-specific morphine metabolitesDirection of switch from 1 opioid to anotherInter-patient variability in pharmacologic response to opioidsIncomplete cross- tolerance among mu opioids
41Utilizing Equianalgesic Doses Incomplete cross-tolerance & inter-patient variability require use of conservative dosing when converting from one opioid to anotherEquianalgesic dose a starting point for opioid rotationIntended as General GuideCalculated dose of new drug based on EDT must be reduced, then titrate the new opioid as neededClosely follow patients during periods of dose adjustmentsFollow conversion instructions in individual ER/LA opioid PI, when provided
42Guidelines for Opioid Rotation Reduce calculated equianalgesic dose by 25%-50%*Calculate equianalgesic dose of new opioid from EDTSelect % reduction based on clinical judgmentCloser to 50% reduction if patient isCloser to 25% reduction if patientReceiving a relatively high dose of current opioid regimenElderly or medically frailDoes not have these characteristicsIs switching to a different administration route of same drug*75%-90% reduction for methadone
43Guidelines for Opioid Rotation, cont’d If switching to methadone:Reduce calculated equianalgesic dose by 75%-90%For patients on very high opioid doses (e.g., ≥1,000 mg morphine equivalents/d), be cautious converting to methadone ≥100 mg/dConsider inpatient monitoring, including serial EKG monitoringIf switching to transdermal:Fentanyl, calculate dose conversion based on equianalgesic dose ratios included in the PIBuprenorphine, follow instructions in the PI
44Guidelines for Opioid Rotation, cont’d Have a strategy to frequently assess analgesia, AEs and withdrawal symptomsTitrate new opioid dose to optimize outcomes & safetyDose for breakthrough pain (BTP) using a short-acting, immediate release preparation is 5%-15% of total daily opioid dose, administered at an appropriate intervalIf oral transmucosal fentanyl product is used for BTP, begin dosing lowest dose irrespective of baseline opioid doseNEVER use ER/LA opioids for BTP
45Breakthrough Pain in Chronic Pain Patients Patients on stable ATC opioids may experience BTPTherapiesConsider addingDisease progression or a new or unrelated painDirected at cause of BTP or precipitating factorsNonspecific symptomatic therapies to lessen impact of BTPPRN IR opioid trial based on analysis of benefit versus riskRisk for aberrant drug-related behaviorsHigh-risk: only in conjunction w/ frequent monitoring & follow-upLow-risk: w/ routine follow-up & monitoringNonopioid drug therapiesNonpharmacologic treatments
46Reasons for Discontinuing ER/LA Opioids No progress toward therapeutic goalsIntolerable & Unmanageable AEsPain level decreases in stable patientsNonadherence or unsafe behaviorAberrant behaviors suggestive of addiction &/or diversion1 or 2 episodes of increasing dose without prescriber knowledgeSharing medicationsUnapproved opioid use to treat another symptom (e.g., insomnia)Use of illicit drugs or unprescribed opioidsRepeatedly obtaining opioids from multiple outside sourcesPrescription forgeryMultiple episodes of prescription loss
48Informed ConsentBefore initiating a trial of opioid analgesic therapy, obtain informed consent to establish:Analgesic & functional goals of treatmentThe potential for & how to manage:Common opioid-related AEs (e.g., constipation, nausea, sedation)Other serious risks (e.g., abuse, addiction, respiratory depression, overdose)AEs after long-term or high-dose opioid therapy (e.g., hyperalgesia, endocrinologic or sexual dysfunction)ExpectationsPotential risksAlternatives to opioids
50Consider a PPAReinforce expectations for appropriate & safe opioid useObtain opioids from a single prescriberFill opioid prescriptions at a designated pharmacySafeguard opioidsDo not store in medicine cabinetKeep locked (e.g., use a medication safe)Do not share or sell medicationInstructions for disposal when no longer neededCommitments to return for follow-up visitsComply w/ appropriate monitoringE.g., random UDT & pill countsFrequency of prescriptionsEnumerate behaviors that may lead to opioid discontinuationAn exit strategy
51Monitor Patients During Opioid Therapy Therapeutic risks & benefits do not remain staticIdentify patientsPeriodically assess continued need for opioid analgesicAffected by change in underlying pain condition, coexisting disease, or psychologic/social circumstancesWho are benefiting from opioid therapyWho might benefit more w/ restructuring of treatment or receiving additional services (e.g., addiction treatment)Whose benefits from treatment are outweighed by risksRe-evaluate underlying medical condition if clinical presentation changesPeriodically evaluate: Pain control, Document pain intensity, pattern, & effects, Functional outcomes, Document level of functioning, Assess progress toward achieving therapeutic goalsHealth-related QOL, AE frequency & intensity, Adherence to prescribed therapiesPatients requiring more frequent monitoring:High riskOn high opioid doses
52Anticipate & Treat Common AEs Constipationmost common after opioid initiation or dose increases, does not resolve with timeNausea & vomitingtend to diminish over days or weeksInitiate a bowel regimen before constipation developsIncrease fluid & fiber intake, stool softeners, & laxativesOral & rectal antiemetic therapies as neededOpioid antagonists may help prevent/treat opioid-induced bowel dysfunctionDrowsiness & sedationtend to wane over timePruritus & myoclonustend to diminish over days or weeksThis slide combines slides 83 and 82Counsel patients about driving, work & home safety as well as risks of concomitant exposure to other drugs & substances w/ sedating effectsTreatment strategies for either condition largely anecdotalChou R, et al. J Pain. 2009;10:113-30
53Monitor Adherence and Aberrant Behavior Routinely monitor patient adherence to treatment planRecognize & document aberrant drug-related behaviorIn addition to patient self-report also use:State PDMPs, where availableUDTPositive for nonprescribed drugsPositive for illicit substanceNegative for prescribed opioidFamily member or caregiver interviewsMonitoring tools such as the COMM, PADT, PMQ, or PDUQMedication reconciliation (e.g., pill counts)PADT=Pain Assessment & Documentation Tool
54Address Aberrant Drug-Related Behavior Behavior outside the boundaries of agreed-on treatment plan:Behaviors that are less indicative of aberrancyBehaviors that are more indicative of aberrancyUnsanctioned dose escalations or other noncompliance w/ therapy on 1 or 2 occasionsMultiple dose escalations or other noncompliance w/ therapy despite warningsUnapproved use of the drug to treat another symptomPrescription forgeryOpenly acquiring similar drugs from other medical sourcesObtaining prescription drugs from nonmedical sources
55Prescription Drug Monitoring Programs (PDMPs) 49 states & 1 territory have legislation authorizing a PDMP43 states have an operational PDMPIndividual state laws determineWho has access to PDMP informationWhich drug schedules are monitoredWhich agency administers the PDMPWhether prescribers are required to register w/ the PDMPWhether prescribers are required to access PDMP information in certain circumstancesWhether unsolicited PDMP reports are sent to prescribers
56PDMP Benefits Prescribers can check their own prescribing Hx Record of a patient’s controlled substance prescriptionsProvide warnings of potential misuse/abuseSome are available online 24/7Opportunity to discuss w/ patientExisting prescriptions not reported by patientMultiple prescribers/pharmaciesDrugs that increase overdose risk when taken togetherPatient pays for drugs of abuse w/ cashPrescribers can check their own prescribing Hx
57PDMP Unsolicited Patient Threshold Reports Reports automatically generated on patients who cross certain thresholds when filling prescriptions. Available in some states.ed to prescribers to whom prescriptions were attributed.Prescribers review records to confirm it is your patient & you wrote the prescription(s) attributed to youIf inaccurate, contact PDMP.If you wrote the prescription(s), patient safety may dictate need to discuss the patient w/ other prescribers listed on report.Decide who will continue to prescribe for the patient & who might address drug abuse concerns.Using Patient Threshold ReportsIf you receive a Patient Threshold Report, please review your records to confirm that this is your patient and that you wrote the prescription(s) attributed to you. If you find that any of the records are inaccurate, contact the Prescription Monitoring Program immediately.If you did write the prescriptions, patient safety generally dictates the need to discuss the patient with the other doctors listed on the report. During this discussion, you should decide collectively who will continue to provide prescriptions for the patient and who might address any concerns about drug abuse with them. You may also want to keep the report in your patient's chart. The goal is to get people the treatment they need if they have a substance abuse problem.
58Rationale for Urine Drug Testing (UDT) Help to identify drug misuse/addictionPrior to starting opioid treatmentAssist in assessing adherence during opioid therapyAs requirement of therapy w/ an opioidSupport decision to referUDT frequency is based on clinical judgmentDepending on patient’s display of aberrant behavior and whether it is sufficient to document adherence to treatment planCheck state regulations for requirements
59Main Types of UDT Methods Initial testing w/ IA drug panels:Classify substance as present or absent according to cutoffMany do not identify individual drugs within a classSubject to cross-reactivityEither lab based or at POCIdentify specific drugs &/or metabolites w/ sophisticated lab-based testing; e.g., GC/MS or LC/MS*Specifically confirm the presence of a given druge.g., morphine is the opiate causing a positive IA*Identify drugs not included in IA testsWhen results are contested* GC/MS=gas chromatography/ mass spectrometry IA=immunoassay LC/MS=liquid chromatography/ mass spectrometry
60Detecting Opioids by UDT Most common opiate IA drug panelsGC/MS or LC/MS will identify specific opioidsDetect “opiates” morphine & codeine, but doesn’t distinguishConfirm presence of a drug causing a positive IADo not reliably detect semisynthetic opioidsIdentify opioids not included in IA drug panels, including semisynthetic & synthetic opioidsSpecific IA panels can be ordered for someDo not detect synthetic opioids (e.g., methadone, fentanyl)Only a specifically directed IA panel will detect syntheticsLab can identify specific opioids at physician request
61Interpretation of UDT Results Positive resultPositive resultDemonstrates recent useMost drugs in urine have detection times of 1-3 dChronic use of lipid-soluble drugs: test positive for ≥1 wkDoes not diagnoseDrug addiction, physical dependence, or impairmentDoes not provide enough information to determineExposure time, dose, or frequency of useNegative result for prescribed opioidDoes not diagnose diversionMore complex than presence or absence of a drug in urineMay be due to maladaptive drug-taking behaviorBingeing, running out earlyOther factors: eg, cessation of insurance, financial difficultiesDemonstrates recent useMost drugs in urine have detection times of 1-3 dChronic use of lipid- soluble drugs: test positive for ≥1 wkDoes not diagnoseDrug addiction, physical dependence, or impairmentDoes not provide enough information to determineExposure time, dose, or frequency of useNegative resultDoes not diagnose diversionMore complex than presence or absence of a drug in urineMay be due to maladaptive drug-taking behaviorBingeing, running out earlyOther factors: e.g., cessation of insurance, financial difficulties
62Interpretation of UDT Results, cont’d Be awareTesting technologies & methodologies evolveDifferences exist between IA test menu panels varyCross-reactivity patternsMaintain list of all patient’s prescribed & OTC drugsAssist to identify false-positive resultCutoff levelsTime taken to eliminate drugsDocument time of last use & quantity of drug(s) takenOpioid metabolism may explain presence of apparently unprescribed drugs
63Examples of Metabolism of Opioids CodeineMorphine6-MAM*Heroint½=25-30 mint½=3-5 minHydrocodoneHydromorphoneOxycodoneOxymorphoneNot comprehensive pathways, but may explain presence of apparently unprescribed drugs*6-MAM=6-monoacetylmorphine
64Interpretation of UDT Results Use UDT results in conjunction w/ other clinical informationInvestigate unexpected resultsDiscuss w/ the labSchedule appointment w/ patient to discuss unexpected/abnormal resultsChart results, interpretation, & actionDo not ignore the unexpected positive resultMay necessitate closer monitoring &/or referral to a specialistGourlay DL, et al. Urine Drug Testing in Clinical Practice. The Art & Science of Patient Care. Ed
65Be Ready to ReferBe familiar w/ referral sources for abuse or addiction that may arise from use of ER/LA opioidsSAMHSA substance abuse treatment facility locatorSAMHSA mental health treatment facility locator
67Use Patient Counseling Document to help counsel patients Download: opioidrems.com/IwgUI/rems/pdf/patient_counseling_document.pdfThe Patient Counseling Document (PCD) on Extended-Release/Long Acting (ER/LA) Opioid Analgesics is a toolunique to this REMS designed to facilitate importantdiscussions with your patients for whom you select an ER/LA opioid analgesic. The PCD should be provided to andreviewed with the patient and/or their caregiver at the timeof prescribing. It contains important safety informationabout the drug products subject to this REMS and includesspace for you to write additional information to help yourpatients use their ER/LA opioid analgesic safely.Order hard copies:Collaborative for REMS Education
68Counsel Patients About Proper Use ExplainInstruct patients/ caregivers toProduct-specific information about the prescribed ER/LA opioidHow to take the ER/LA opioid as prescribedImportance of adherence to dosing regimen, handling missed doses, & contacting their prescriber if pain cannot be controlledRead the ER/LA opioid Medication Guide received from pharmacy every time an ER/LA opioid is dispensedAt every medical appointment explain all medications they takeCollaborative for REMS Education
69Counsel Patients About Proper Use, cont’d Counsel patients/caregivers:On the most common AEs of ER/LA opioidsAbout the risk of falls, working w/ heavy machinery, & drivingCall the prescriber for advice about managing AEsInform the prescriber about AEsPrescribers should report serious AEs to the FDA: HowToReport/DownloadForms/UCM pdf or FDA-1088
70Warn PatientsNever break, chew, or crush an oral ER/LA tablet/capsule, or cut or tear patches prior to useMay lead to rapid release of ER/LA opioid causing overdose & deathWhen a patient cannot swallow a capsule whole, prescribers should refer to PI to determine if appropriate to sprinkle contents on applesauce or administer via feeding tubeUse of other CNS depressants* w/ ER/LA opioids can cause overdose & deathUse other CNS depressants, including other opioids, under the instruction of their prescriberThe use of other CNS depressants such as sedative-hypnotics and anxiolytics, alcohol, or illegal drugs with ER/LA opioid analgesics can cause overdose and death.*eg, sedative-hypnotics & anxiolytics, alcohol, illegal drugs
71Warn Patients, cont’d Misuse of ER/LA opioids can lead to death TAKE 1 TABLET BY MOUTH EVERY 12 HOURSOXYCONTIN 10 MGQty: 60 TABLETSMisuse of ER/LA opioids can lead to deathTake exactly as directedCounsel patients/caregivers on risk factors, signs, & symptoms of overdose & opioid-induced respiratory depression, GI obstruction, & allergic reactionsCall 911 or poison controlDo not abruptly stop or reduce the ER/LA opioid useDiscuss how to safely taper the dose when discontinuing
72Protecting the Community Caution PatientsSharing ER/LA opioids w/ others may cause them to have serious AEsIncluding deathSelling or giving away ER/LA opioids is against the lawStore ER/LA opioids in a safe & secure place away from children, family members, household visitors, & petsProtect ER/LA opioids from theftDispose of any ER/LA opioids when no longer neededRead product-specific disposal information included w/ ER/LA opioid
74Educate Patients & Families Rx medicines should only be taken when prescribed to you by a providerTaking a pill prescribed for someone else is drug abuse and illegal, “even just once”Misusing Rx drugs can be as dangerous as illegal “street” drugsMixing Rx opioids w/ alcohol or w/ sedatives/hypnotics is potentially fatalPrescription medications should only be taken by a patient prescribed them by a provider, per the provider’s instructions.They should not be used for other reasons than as prescribed, such as emotional issues or sleep.They should not be used by someone other than the patient, even if it is for the same indication. Taking a pill prescribed for someone else is drug abuse, and illegal, even when just on one occasion.A common myth among teens is that prescription medications are a safer way to get high than illicit drug use. Teens do not fully perceive the harmfulness from taking a prescription drug without a doctor’s prescription.Mixing prescription drugs with alcohol increases risk of fatal overdose.An overlapping opioid or sedative/hypnotic prescription is strongly associate with risk of overdose.
75Educate Parents: Not in My House Step 1: MonitorNote how many pills in each prescription bottle or pill packetKeep track of refills for all household membersIf your teen has been prescribed a drug, coordinate & monitor dosages & refillsMake sure friends & relatives—especially grandparents—are aware of the risksThe ready availability of prescription medications in teens’ own homes highlights the need for increased educational efforts targeting parents and other family members regarding safeguarding and monitoring prescription medications in the home, so that they do not act as “unintentional enablers.”MONITOR:Parents are in an influential position to immediately help reduce teen access toprescription drugs because these drugs are found in the home.Start by taking note of how many pills are in each of your prescription bottles or pill packets.Keep track of your refills. This goes for your own medication, as well as for your teens and other members of the household. Needing to refill medication more often than expected could indicate a problem.If your teen has been prescribed a drug, be sure you control the medication, and monitor dosages and refills.Make sure your friends and relatives—especially grandparents—are also aware of the risks. Encourage them to regularly monitor their own medicine cabinets.If there are other households your teen has access to, talk to those families as well about the importance of helping safeguard their medications.If your teen visits other households, talk to the families about safeguarding their medications
76Educate Parents: Not in My House, cont’d Step Two: Secure Step Three: DisposeDo not store prescription meds in the medicine cabinetKeep meds in a safe place (e.g., locked cabinet)Take inventory of all prescription drugs in your homeTell relatives, especially grandparents, to lock meds or keep in a safe placeEncourage parents of your teen’s friends to secure medsDiscard expired or unused medsSECURE:Teens abuse prescription drugs because they are easily accessible and either free or inexpensive. Approach securing your prescriptions the same way you would other valuables in your home, like jewelry or cash.Take prescription medications out of the medicine cabinet and hide them in a place only you know about.If possible, keep all medicines in a safe place, such as a locked cabinet your teen cannot access.Tell relatives, especially grandparents, to lock their medications or keep them in a safe place.Talk to the parents of your teenager’s friends. Encourage them to secure their prescriptionsHowever, in the survey of Massachusetts parents by the Partnership at DrugFree.org, 34% of respondents say that grandparents use prescription pain relievers, but only 19% have spoken to grandparents about safeguarding their medications.Safely disposing of expired or unused prescription medications is a critical step to decrease the opportunity for your teens or their friends to abuse your medications.DISPOSE:After taking an inventory of all of the prescription drugs in your home, discard expired or unused prescription drugs, when your teens are not home.
77ER/LA Opioid Drug Disposal National Prescription Drug Take-Back Day: “Got Drugs?”Locations TBAMore information at:Drug drop boxes in some local police departments, to find a box near you:oror
78Prescription drug disposal when a program or drop box is unavailable: If take-back program or drop box unavailable, throw out in household trashTake drugs out of original containersMix w/ undesirable substance, e.g., used coffee grounds or kitty litterLess appealing to children/pets, & unrecognizable to people who intentionally go through your trashPlace in sealable bag, can, or other containerPrevent leaking or breaking out of garbage bagBefore throwing out a medicine containerScratch out identifying info on labelIf no instructions are given on the drug label and no local take-back programs are available, the drugs can be disposed of in household trash. First, they should be removed from their original containers and mixed with an undesirable substance (eg, used coffee grounds or kitty litter), so that the medication is less appealing to children and pets, and unrecognizable to people who may intentionally go through trash. Then they should be placed in a sealable bag, can, or other container to prevent the medication from leaking or breaking out of a garbage bag. Before throwing out a medicine container, scratch out all identifying information on the prescription label to protect privacy of personal health information and prevent unauthorized refills. When in doubt about proper disposal, parents should talk to their pharmacist.
79Prescription Drug Disposal FDA lists especially harmful medicines—in some cases fatal w/ just 1 dose—if taken by someone other than the patientInstruct patients to check medication guideFlush down sink/toilet if no take-back program availableAs soon as they are no longer neededSo cannot be accidentally taken by children, pets, or othersIncludes transdermal adhesive skin patchesUsed patch worn for 3 d still contains enough opioid to harm/kill a childDispose of used patches immediately after removing from skinFold patch in half so sticky sides meet, then flush down toiletDo NOT place used or unneeded patches in household trashException is Butrans: can seal in Patch-Disposal Unit provided & dispose of in the trash
80Disposal UpdatesIn Dec 2012, DEA published a Notice of Proposed Rulemaking for Disposal of Controlled SubstancesThe Secure & Responsible Drug Disposal Act of 2010 would expand options to collect controlled substances from ultimate users for disposal to include:Take-back eventsMail-back programsCollection receptacle locationsCheck back atDEA. Federal Register. 2012; 77(246): Proposed Rules. Disposal of Controlled Substances.
82General ER/LA Opioid Drug Information Prescribers should be knowledgeable about general characteristics, toxicities, & drug interactions for ER/LA opioid products:Respiratory depression is the most serious opioid AEConstipation is the most common long-term AEER/LA opioid analgesic products are scheduled under the Controlled Substances Act & can be misused & abusedCan be immediately life-threateningShould be anticipated
83For Safer Use: Know Drug Interactions, PK, & PD CNS depressants* can potentiate sedation & respiratory depressionSome ER products rapidly release opioid (dose dump) when exposed to alcoholSome drug levels may increase without dose dumpingUse w/ MAOIs may increase respiratory depressionCertain opioids w/ MAOIs can cause serotonin syndromeCan reduce efficacy of diureticsInducing release of antidiuretic hormoneCertain opioids with MAOIs may cause serotonin syndrome.Methadone & buprenorphine can prolong QTc intervalDrugs that inhibit or induce CYP enzymes can increase or lower blood levels of some opioids
84Opioid Tolerant Opioid-tolerant patients are those taking at least Tolerance to sedating & respiratory-depressant effects is critical to safe use of certain ER/LA opioid products, dosage unit strengths, or dosesPatients must be opioid tolerant before usingAny strength of transdermal fentanyl or hydromorphone ERCertain strengths or daily doses of other ER productsOpioid-tolerant patients are those taking at least60 mg oral morphine/day25 mcg transdermal fentanyl/hr30 mg oral oxycodone/day8 mg oral hydromorphone/day25 mg oral oxymorphone/dayAn equianalgesic dose of another opioid
85Key Instructions: ER/LA Opioids Individually titrate to a dose that provides adequate analgesia & minimizes adverse reactionsTimes required to reach steady-state plasma concentrations are product-specificRefer to product information for titration intervalContinually re-evaluate to assess maintenance of pain control & emergence of AEs
87Common Drug Information for This Class Limitations of usageDosage reduction for hepatic or renal impairmentRelative potency to oral morphineNot for use as an as-needed analgesicNot for mild pain or pain not expected to persist for an extended durationNot for use in treating acute painSee individual drug PIIntended as general guideFollow conversion instructions in individual PIIncomplete cross-tolerance & inter-patient variability require conservative dosing when converting from 1 opioid to anotherHalve calculated comparable dose & titrate new opioid as needed
88Solid Oral Dosage Forms Swallow tablets & capsules wholeCrushing, chewing, breaking, cutting or dissolving may result in rapid release & absorption of a potentially fatal opioid doseSome capsules* can be opened & pellets sprinkled on applesauce for patients who can reliably swallow without chewing & used immediately*See individual PIExposure of some products to alcoholic beverages or medications containing alcohol may result in rapid release & absorption of a potentially fatal opioid doseDispose of unused product at Drug-Take-Back Events. If not available, flush down toilet
89Transdermal Dosage Forms Do not cut, damage, chew, or swallowExertion or exposure to external heat can lead to fatal overdoseRotate location of applicationPrepare skin: clip - not shave - hair & wash area w/ waterMonitor patients w/ fever for signs or symptoms of increased opioid exposureDispose of unused product at Drug-Take-Back EventsIf not available, flush down toiletButrans: seal in patch-disposal unit & dispose of in trashNote: Metal foil backings are not safe for use in MRIs
90Drug Interactions Common to This Class Concurrent use w/ other CNS depressants can increase risk of respiratory depression, hypotension, profound sedation, or comaReduce initial dose of one or both agentsAvoid using partial agonists & mixed agonist/antagonist analgesics† together, may reduce analgesic effect or precipitate withdrawalMay enhance neuromuscular blocking action of skeletal muscle relaxants & increase respiratory depressionConcurrent use w/ anticholinergic medication increases risk of urinary retention & severe constipationMay lead to paralytic ileus†Buprenorphine, pentazocine, nalbuphine, butorphanol
91Drug Information Common to This Class Use in opioid-tolerant patientsContraindicationsSee individual PI for products which:Have strengths or total daily doses only for use in opioid-tolerant patientsAre only for use in opioid-tolerant patients at all strengthsSignificant respiratory depressionAcute or severe asthma in an unmonitored setting or in absence of resuscitative equipmentKnown or suspected paralytic ileusHypersensitivity (e.g., anaphylaxis)See individual PI for additional contraindications
93Specific Characteristics Know for opioid products you prescribe:Drug substanceFormulationStrengthDosing intervalSpecific information about product conversions, if availableSpecific drug interactionsKey instructionsUse in opioid-tolerant patientsProduct-specific safety concernsRelative potency to morphineFor detailed information, refer to online PI: DailyMed atat
94Morphine Sulfate ER Capsules (Avinza) Dosing intervalOnce a dayKey instructionsInitial dose in opioid non-tolerant patients is 30 mgTitrate using a minimum of 3-d intervalsSwallow capsule whole (do not chew, crush, or dissolve)May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing; use immediatelyMDD:* 1600 mg (renal toxicity of excipient, fumaric acid)Drug interactionsAlcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dosePGP* inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-foldOpioid-tolerant90 mg & 120 mg capsules for use in opioid-tolerant patients onlyProduct-specific safety concernsNone* MDD=maximum daily dose; PGP= P-glycoprotein
95Buprenorphine Transdermal System (Butrans) Dosing intervalOne transdermal system every 7 dKey instructionsInitial dose in opioid non-tolerant patients on <30 mg morphine equivalents & in mild-moderate hepatic impairment: 5 mcg/hWhen converting from 30 mg-80 mg morphine equivalents, first taper to 30 mg morphine equivalent, then initiate w/ 10 mcg/hTitrate after a minimum of 72 h prior to dose adjustmentMaximum dose: 20 mcg/h due to risk of QTc prolongationApplicationApply only to sites indicated in PIApply to intact/non-irritated skinPrep skin by clipping hair; wash site w/ water onlyRotate application site (min 3 wks before reapply to same site)Do not cutAvoid exposure to heatDispose of patches: fold adhesive side together & flush down toilet
96Buprenorphine Transdermal System (Butrans) cont’d Drug interactionsCYP3A4 inhibitors may increase buprenorphine levelsCYP3A4 inducers may decrease buprenorphine levelsBenzodiazepines may increase respiratory depressionClass IA & III antiarrythmics, other potentially arrhythmogenic agents, may increase risk of QTc prolongation & torsade de pointeOpioid-tolerant10 mcg/h & 20 mcg/h for use in opioid-tolerant patients onlyDrug-specific safety concernsQTc prolongation & torsade de pointeHepatotoxicityApplication site skin reactionsRelative potency: oral morphineEquipotency to oral morphine not established
97Methadone Hydrochloride Tablets (Dolophine) Dosing intervalEvery 8 to 12 hKey instructionsInitial dose in opioid non-tolerant patients: 2.5 to 10 mgConversion of opioid-tolerant patients using equianalgesic tables can result in overdose & death. Use low doses according to table in full PIHigh inter-patient variability in absorption, metabolism, & relative analgesic potencyOpioid detoxification or maintenance treatment only provided in a federally certified opioid (addiction) treatment program (CFR, Title 42, Sec 8)Drug interactionsPharmacokinetic drug-drug interactions w/ methadone are complexCYP 450 inducers may decrease methadone levelsCYP 450 inhibitors may increase methadone levelsAnti-retroviral agents have mixed effects on methadone levelsPotentially arrhythmogenic agents may increase risk for QTc prolongation & torsade de pointeBenzodiazepines may increase respiratory depressionDelayed/prolonged respiratory depression with methadone compared to others
98Methadone Hydrochloride Tablets (Dolophine) cont’d Opioid-tolerantRefer to full PIDrug-specific safety concernsQTc prolongation & torsade de pointePeak respiratory depression occurs later & persists longer than analgesic effectClearance may increase during pregnancyFalse-positive UDT possibleRelative potency: oral morphineVaries depending on patient’s prior opioid experienceDelayed/prolonged respiratory depression with methadone compared to others
99Fentanyl Transdermal System (Duragesic) Dosing intervalEvery 72 h (3 d)Key instructionsUse product-specific information for dose conversion from prior opioidHepatic or renal impairment: use 50% of dose if mild/moderate, avoid use if severeApplicationApply to intact/non-irritated/non-irradiated skin on a flat surfacePrep skin by clipping hair, washing site w/ water onlyRotate site of applicationTitrate using no less than 72 h intervalsDo not cutAvoid exposure to heatAvoid accidental contact when holding or caring for childrenDispose of used/unused patches: fold adhesive side together & flush down toilet
100Fentanyl Transdermal System (Duragesic), cont’d Key instructionsSpecific contraindications:Patients who are not opioid-tolerantManagement ofAcute or intermittent pain, or patients who require opioid analgesia for a short period of timePost-operative pain, out-patient, or day surgeryMild painDrug interactionsCYP3A4 inhibitors may increase fentanyl exposureCYP3A4 inducers may decrease fentanyl exposureOpioid-tolerantAll doses indicated for opioid-tolerant patients onlyDrug-specific safety concernsAccidental exposure due to secondary exposure to unwashed/unclothed application siteIncreased drug exposure w/ increased core body temp or feverBradycardiaApplication site skin reactionsRelative potency: oral morphineSee individual PI for conversion recommendations from prior opioid
101Morphine Sulfate ER-Naltrexone Tablets (Embeda) Dosing intervalOnce a day or every 12 hKey instructionsInitial dose as first opioid: 20 mg/0.8 mgTitrate using a minimum of 3-d intervalsSwallow capsules whole (do not chew, crush, or dissolve)Crushing or chewing will release morphine, possibly resulting in fatal overdose, & naltrexone, possibly resulting in withdrawal symptomsMay open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediatelyDrug interactionsAlcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dosePGP inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-foldOpioid-tolerant100 mg/4 mg capsule for use in opioid-tolerant patients onlyProduct-specific safety concernsNoneEmphasize 3-day minimum interval dose titration
102Hydromorphone Hydrochloride ER Tablets (Exalgo) Dosing intervalOnce a dayKey instructionsUse conversion ratios in individual PIStart patients w/ moderate hepatic impairment on 25% dose prescribed for patient w/ normal functionRenal impairment: start patients w/ moderate on 50% & patients w/ severe on 25% dose prescribed for patient w/ normal functionTitrate using a minimum of 3 to 4 d intervalsSwallow tablets whole (do not chew, crush, or dissolve)Do not use in patients w/ sulfite allergy (contains sodium metabisulfite)Drug interactionsNoneOpioid-tolerantAll doses are indicated for opioid-tolerant patients onlyProduct-specific adverse reactionsAllergic manifestations to sulfite componentRelative potency: oral morphine~5:1 oral morphine to hydromorphone oral dose ratio, use conversion recommendations in individual product information
103Morphine Sulfate ER Capsules (Kadian) Dosing intervalOnce a day or every 12 hKey instructionsPI recommends not using as first opioidTitrate using minimum of 2-d intervalsSwallow capsules whole (do not chew, crush, or dissolve)May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediatelyDrug interactionsAlcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose of morphinePGP inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-foldOpioid-tolerant100 mg & 200 mg capsules for use in opioid-tolerant patients onlyProduct-specific safety concernsNone
104Morphine Sulfate CR Tablets (MS Contin) Dosing intervalEvery 8 h or every 12 hKey instructionsProduct information recommends not using as first opioid.Titrate using a minimum of 2-d intervalsSwallow tablets whole (do not chew, crush, or dissolve)Drug interactionsPGP inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-foldOpioid-tolerant100 mg & 200 mg tablet strengths for use in opioid-tolerant patients onlyProduct-specific safety concernsNone
105Tapentadol ER Tablets (Nucynta ER) Dosing intervalEvery 12 hKey instructions50 mg every 12 h is initial dose in opioid non-tolerant patientsTitrate by 50 mg increments using minimum of 3-d intervalsMDD: 500 mgSwallow tablets whole (do not chew, crush, or dissolve)Take 1 tablet at a time w/ enough water to ensure complete swallowing immediately after placing in mouthDose once/d in moderate hepatic impairment (100 mg/d max)Avoid use in severe hepatic & renal impairmentDrug interactionsAlcoholic beverages or medications w/ alcohol may result in rapid release & absorption of a potentially fatal dose of tapentadolContraindicated in patients taking MAOIsOpioid-tolerantNo product-specific considerationsProduct-specific safety concernsRisk of serotonin syndromeAngio-edemaRelative potency: oral morphineEquipotency to oral morphine has not been established
106Oxymorphone Hydrochloride ER Tablets (Opana ER) Dosing intervalEvery 12 h dosing, some may benefit from asymmetric (different dose given in AM than in PM) dosingKey instructionsUse 5 mg every 12 h as initial dose in opioid non-tolerant patients & patients w/ mild hepatic impairment & renal impairment (creatinine clearance <50 mL/min) & patients >65 yrsSwallow tablets whole (do not chew, crush, or dissolve)Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouthTitrate using a minimum of 2-d intervalsContraindicated in moderate & severe hepatic impairmentDrug interactionsAlcoholic beverages or medications w/ alcohol may result in absorption of a potentially fatal dose of oxymorphoneOpioid-tolerantNo product-specific considerationsProduct-specific safety concernsNoneRelative potency: oral morphineApproximately 3:1 oral morphine to oxymorphone oral dose ratio
107Oxycodone Hydrochloride CR Tablets (OxyContin) Dosing intervalEvery 12 hKey instructionsOpioid-naïve patients: initiate treatment w/ 10 mg every 12 hTitrate using a minimum of 1 to 2 d intervalsHepatic impairment: start w/ ⅓-½ usual dosageRenal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosageConsider other analgesics in patients w/ difficulty swallowing or underlying GI disorders that predispose to obstruction. Swallow tablets whole (do not chew, crush, or dissolve)Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouthDrug interactionsCYP3A4 inhibitors may increase oxycodone exposureCYP3A4 inducers may decrease oxycodone exposureOpioid-tolerantSingle dose >40 mg or total daily dose >80 mg for use in opioid- tolerant patients onlyProduct-specific safety concernsChoking, gagging, regurgitation, tablets stuck in throat, difficulty swallowing tabletContraindicated in patients w/ GI obstructionRelative potency: oral morphineApproximately 2:1 oral morphine to oxycodone oral dose ratio
108Summary Prescription opioid abuse & overdose is a national epidemic Clinicians must play a role in preventionUnderstand how to assess patients for treatment w/ ER/LA opioidsBe familiar w/ how to initiate therapy, modify dose, & discontinue use of ER/LA opioidsKnow how to manage ongoing therapy w/ ER/LA opioidsKnow how to counsel patients & caregivers about the safe use of ER/LA opioids, including proper storage & disposalBe familiar w/ general & product-specific drug information concerning ER/LA opioids
109Thank you for completing the post-activity assessment for this CO Thank you for completing the post-activity assessment for this CO*RE session. Your participation in this assessment allows CO*RE to report de-identified numbers to the FDA. A strong show of engagement will demonstrate that clinicians have voluntarily taken this important education and are committed to patient safety and improved outcomes.