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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`022272Orig1s027
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`REMS
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`Initial REMS Approval: 07/2012
`Most Recent Modification: 08/2015
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`EXTENDED-RELEASE (ER) AND LONG-ACTING (LA) OPIOID
`ANALGESICS RISK EVALUATION AND MITIGATION
`STRATEGY (REMS)
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`Reference ID: 3805894
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`GOAL
`The goal of this REMS is to reduce serious adverse outcomes resulting from
`inappropriate prescribing, misuse, and abuse of extended-release or long-acting (ER/LA)
`opioid analgesics while maintaining patient access to pain medications. Adverse
`outcomes of concern include addiction, unintentional overdose, and death.
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`I. REMS ELEMENTS
`A. Medication Guide
`A Medication Guide will be dispensed with each ER/LA opioid analgesic
`prescription in accordance with 21 CFR § 208.24.
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`The Medication Guides for ER/LA opioids are part of the ER/LA Opioid
`Analgesic REMS program and will be available through the ER/LA Opioid
`Analgesic REMS website www.ER-LA-opioidREMS.com.
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`B. Elements to Assure Safe Use
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`1. Training will be made available to healthcare providers who prescribe ER/LA
`opioid analgesics.
`a. Training will be considered “REMS-compliant training” under this
`REMS if: 1) it, for training provided by CE providers, is offered by an
`accredited provider to licensed prescribers, 2) it includes all elements
`of the FDA Blueprint for Prescriber Education for Extended-Release
`and Long-Acting Opioid Analgesics (“FDA Blueprint”), 3) it includes
`a knowledge assessment of all of the sections of the FDA Blueprint,
`and 4) it is subject to independent audit to confirm that conditions of
`the REMS training have been met.
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`b. The NDA/ANDA holders of ER/LA opioid analgesic products
`(“NDA/ANDA holders”) will ensure that REMS-compliant training is
`made available to prescribers of ER/LA opioid analgesics and will
`achieve the following performance goals:
`i. Not later than March 1, 2013, the first REMS-compliant
`training will be made available.
`ii. Within two years from the time the first REMS-compliant
`training becomes available, 80,000 prescribers (based on 25%
`of the 320,000 active prescribers in 2011) will have been
`trained;
`iii. Within three years from the time the first REMS-compliant
`training becomes available, 160,000 prescribers (based on 50%
`of the 320,000 active prescribers in 2011) will have been
`trained;
`iv. Within four years from the time the first REMS-compliant
`training becomes available, 192,000 prescribers (based on 60%
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`Reference ID: 3805894
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`of the 320,000 active prescribers in 2011) will have been
`trained.
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`c. The content of the REMS-compliant training will be based on the
`learning objectives established by the FDA Blueprint. The FDA
`Blueprint contains core messages to be conveyed to prescribers in the
`training about the risks and appropriate prescribing practices for the
`safe use of ER/LA opioid analgesics. The NDA/ANDA holders will
`direct providers of REMS-compliant training to the FDA Blueprint,
`via the REMS website (www.ER-LA-opioidREMS.com), and via its
`Request for Grant Applications. No less than annually, NDA/ANDA
`holders will direct providers of REMS-compliant training to consult
`the FDA Blueprint for possible revisions (e.g., changes to the drug
`specific information).
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`d. NDA/ANDA holders will ensure that independent audits of the
`educational materials used by the providers of REMS-compliant
`training are conducted. The audits must:
`i. Be conducted by an auditor independent of the NDA/ANDA
`holders. (Accreditation bodies of CE providers would be
`considered independent of the NDA/ANDA holders and would
`be eligible to conduct the audits.)
`ii. Evaluate:
`1. whether the content of the training covers all
`components of the FDA Blueprint approved as part of
`the REMS;
`2. whether the knowledge assessment measures
`knowledge of all sections of the FDA Blueprint;
`and
`3. for training conducted by CE providers, whether the
`training was conducted in accordance with the
`standards for CE of the Accreditation Council for
`Continuing Medication Education® (ACCME®), or of
`another CE accrediting body appropriate to the
`prescribers’ medical specialty or healthcare profession.
`iii. Be conducted on a random sample of 1) at least 10% of the
`training funded by the NDA/ANDA holders, and 2)
`REMS-compliant training not funded by the NDA/ANDA
`holders but that will be counted towards meeting the
`performance goals in section B.1.b.
`e. To facilitate prescriber awareness of the availability of the REMS and
`REMS-compliant training, within 30 calendar days of the approval of
`the REMS, the NDA/ANDA holders will make available, and then
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`maintain a web site that will contain information about the REMS
`specified below (www.ER-LA-opioidREMS.com):
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`i. A current list of the REMS-compliant training that is supported
`by educational grants from the NDA/ANDA holders, when this
`information becomes available.
`ii. A copy of the Patient Counseling Document (PCD) on
`Extended-Release/Long-Acting Opioid Analgesics.
`iii. A copy of the Prescriber Letters 1, 2, and 3 (when mailed and
`for at least one year thereafter) (see section B.1.f).
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`f. To make prescribers aware of the existence of the REMS and the
`prescriber training that will be made available under the REMS, the
`NDA/ANDA holders will electronically deliver (email or fax), or
`directly mail letters to all DEA-registered prescribers who are
`registered to prescribe Schedule II and III drugs:
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`i. Prescriber Letter 1 will be sent not later than 60 days after the
`initial approval of this REMS, notifying prescribers of the
`existence of the REMS and the fact that prescriber training will
`be offered, and providing a copy of the
`Patient Counseling Document (PCD).
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`ii. Prescriber Letter 2 will be sent not later than 30 days before the
`first prescriber REMS-compliant training required by the
`REMS is offered by providers and will notify prescribers of the
`imminent upcoming availability of accredited REMS CE
`courses.
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`iii. The prescribers will be identified via the DEA Registration
`Database.
`iv. At least annually from the date of initial approval of the REMS,
`the DEA Registration Database will be reviewed and Prescriber
`Letter 3 will be sent to all newly DEA-registered prescribers
`who are registered to prescribe Schedule II and III drugs to
`inform them of the existence of the REMS, provide them the
`Patient Counseling Document (PCD), and notify them of the
`availability of the REMS-compliant training and how to find
`REMS-compliant courses.
`g. To further ensure that prescribers are aware of the existence of the
`ER/LA Opioid Analgesic REMS and the prescriber training that will
`be made available under the REMS, the NDA/ANDA holders will
`electronically deliver (email or fax), or directly mail the following two
`letters to the professional organizations and state licensing entities
`listed in section B.1.g.iii with a request that the information be
`disseminated to their members:
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`Reference ID: 3805894
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`Professional Organization/Licensing Board Letter 1 will be sent
`not later than 60 days after the approval of this REMS,
`notifying prescribers of the existence of the REMS and the fact
`that prescriber training will be offered, and providing a copy of
`the Patient Counseling Document (PCD) on
`Extended-Release/Long-Acting Opioids.
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`Professional Organization/Licensing Board Letter 2 will be sent
`not later than 30 days before the first prescriber REMS-
`compliant training required by the REMS is offered by
`providers and will notify prescribers of the imminent upcoming
`availability of accredited REMS CE courses.
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`The letter and enclosures referenced above, will be sent to the
`following entities:
`a) State Licensing Boards of:
`1) Medicine (allopathic and osteopathic)
`2) Nursing
`3) Dentistry
`b) Associations of State Licensing Boards:
`1) Federation of State Medical Boards
`2) National Council of State Boards of Nursing
`3) American Association of Dental Boards
`c) Learned Societies and Professional Associations, including,
`but not limited to:
`1) American Academy of Addiction Psychiatry
`2) American Academy of Family Physicians
`3) American Academy of Hospice and Palliative Medicine
`4) American Academy of Neurology
`5) American Academy of Nurse Practitioners
`6) American Academy of Nursing
`7) American Academy of Orofacial Pain
`8) American Academy of Pain Management
`9) American Academy of Pain Medicine
`10) American Academy of Physical Medicine and
`Rehabilitation
`11) American Academy of Physician Assistants
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`12) American Association of Colleges of Osteopathic
`Medicine
`13) American Association of Colleges of Nursing
`14) American Association of Poison Control Centers
`15) American Board of Medical Specialties
`16) American Board of Orofacial Pain
`17) American College of Nurse Practitioners
`18) American College of Osteopathic Family Physicians
`19) American College of Physicians
`20) American College of Rheumatology
`21) American Dental Association
`22) American Dental Education Association
`23) American Medical Association
`24) American Medical Directors Association
`25) American Nurses Association
`26) American Nurses Credentialing Center
`27) American Osteopathic Association
`28) American Osteopathic Association of Addiction
`Medicine
`29) American Pain Society
`30) American Society of Addiction Medicine
`31) American Society for Pain Management Nursing
`32) American Society of Anesthesiologists
`33) American Society of Pain Educators
`34) Association of American Medical Colleges
`35) Council of Medical Specialty Societies
`36) Hospice and Palliative Nurses Association
`37) National Association of Managed Care Physicians
`38) National Association of State Controlled Substances
`Authorities
`39) National Commission on Certification of Physician
`Assistants
`40) National Hospice and Palliative Care Organization
`41) American College of Emergency Physicians
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`Reference ID: 3805894
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`42) Society of Emergency Medicine Physician Assistants
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`h. NDA/ANDA holders will ensure that an interim single toll-free
`number call center is implemented no later than July 23, 2012, and a
`fully operational centralized call center is implemented no later than
`90 calendar days after the approval of the REMS.
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`The following materials are part of the ER/LA Opioid Analgesic REMS and are
`appended:
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`- Patient Counseling Document (PCD) on Extended-Release/Long-
`Acting Opioid Analgesics
`- FDA Blueprint for Prescriber Education for Extended-Release and
`Long-Acting Opioid Analgesics
`- Prescriber Letter 1
`- Prescriber Letter 2
`- Prescriber Letter 3
`- Professional Organization/Licensing Board Letter 1
`- Professional Organization/Licensing Board Letter 2
`- ER/LA Opioid Analgesic REMS website
`(www.ER-LA-opioidREMS.com)
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`II. Implementation System
`The ER/LA Opioid Analgesic REMS can be approved without the Elements to Assure
`Safe Use specifically described under FDCA 505-1(f)(3) (B), (C), and (D) of the Act;
`therefore an implementation system is not required.
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`III. Timetable for Submission of Assessments
`REMS assessments will be submitted to the FDA at 6 months and 12 months after the
`initial approval date of the REMS (July 9, 2012), and annually thereafter. To facilitate
`inclusion of as much information as possible, while allowing reasonable time to prepare
`the submission, the reporting interval covered by each assessment will conclude no
`earlier than 60 days before the submission date for that assessment. The NDA holders
`will submit each assessment so that it will be received by the FDA on or before
`the due date based on the initial approval date of the REMS.
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`Reference ID: 3805894
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`Patient Counseling Document (PCD)
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`Patient Counseling Document on Extended-
`Release I Long-Acting Opioid Analgesics
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`Patient Counseling Document on Extended-
`Release I Long-Acting Opioid Analgesics
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`Patient S . -cific Information
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`Read the Medication Guide
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`Take your medicine exactly as prescribed
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`Store your medicine away from children and in a safe
`place
`Flush unused medicine down the toilet
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`Call your healfltcare provider for medial advice
`about side effects. You may report side effects to
`FDA at 1-800-FDA—1 088.
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`Call 91 1 or your local emmg service right away if:
`. You take too much medicine
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`You have trouble breathing, or shortness of breath
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`. A child has taken this medicine by accident
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`Talk to your healthcare provider:
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`.
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`lfthe dose you are taking does not control your pain
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`. About any side effects you may be having
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`. About all the medicines you take, including over-the-
`counter medicines, vitamins, and dietary
`supplements
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`DON’T:
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`. Do not give your medicine to others
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`. Do not take medicine unless itwas prescribed for
`you
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`. Do not stop taking your medicine without talking
`to your healthcare provider
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`. Do not cut, break, chew, crush, dissolve, snort, or
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`If you wnnot swallow your
`inject your medicine.
`medicine whole, talk to your hwlthcare provider.
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`. Do not drink alcohol while taking this medicine
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`Take this card with you every time you see your
`healthcare provider and tell him/her:
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`0 Your complete medical and family history,
`including any history of substance abuse or
`mental illness
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`If you are pregnant or are planning to become
`pregnant
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`The cause, severity, and nature of your pain
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`Your treatment goals
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`All the medicines you take, including over-the-
`counter (non-prescription) medicines, vitamins,
`and dietary supplements
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`Any side effects you may be having
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`Take your opioid pain medicine exactly as
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`For additional information on your medicine go to:
`dailymed.nlm.nih.gov
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`prescribed by your healthcare provider.
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`Reference ID: 3805894
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`FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
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`Introduction for the FDA Blueprint for Prescriber Education for
`Extended-Release and Long-Acting Opioid Analgesics
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`08/2015
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`In April 2011, FDA announced the elements of a Risk Evaluation and Mitigation Strategy
`(REMS) to ensure that the benefits of extended-release and long-acting (ER/LA) opioid
`analgesics outweigh the risks. The REMS supports national efforts to address the prescription
`drug abuse epidemic.
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`As part of the REMS, all ER/LA opioid analgesic companies must provide:
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`• Education for prescribers of these medications, which will be provided through accredited
`continuing education (CE) activities supported by independent educational grants from
`ER/LA opioid analgesic companies.
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`•
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`Information that prescribers can use when counseling patients about the risks and benefits
`of ER/LA opioid analgesic use.
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`FDA developed core messages to be communicated to prescribers in the Blueprint for
`Prescriber Education (FDA Blueprint), published the draft FDA Blueprint for public comment,
`and considered the public comments when finalizing the FDA Blueprint. This final FDA Blueprint
`contains the core educational messages. It is approved as part of the ER/LA Opioid Analgesic
`REMS and will remain posted on the FDA website for use by CE providers to develop the actual
`CE activity. A list of all REMS-compliant CE activities that are supported by independent
`educational grants from the ER/LA opioid analgesic companies to accredited CE providers will
`be posted at www.ER-LA-opioidREMS.com as that information becomes available.
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`The CE activities provided under the FDA Blueprint will focus on the safe prescribing of ER/LA
`opioid analgesics and consist of a core content of about three hours. The content is directed to
`prescribers of ER/LA opioid analgesics, but also may be relevant for other healthcare
`professionals (e.g., pharmacists). The course work is not intended to be exhaustive nor a
`substitute for a more comprehensive pain management course.
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`Accrediting bodies and CE providers will ensure that the CE activities developed under this
`REMS will be in compliance with the standards for CE of the Accreditation Council for
`Continuing Medical Education (ACCME) 1,2 or another CE accrediting body as appropriate to the
`prescribers’ medical specialty or healthcare profession.
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`For additional information from FDA, including more detailed Questions and Answers about the
`REMS for ER/LA Opioid Analgesics, see
`http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm.
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`1Accreditation Council for Continuing Medical Education. 2015. Accreditation Requirements. Criteria for CME Providers-Accreditation
`Criteria. Accessed on May 29, 2015.
`2Accreditation Council for Continuing Medical Education. 2015. Accreditation Requirements. Criteria for CME Providers-Standards
`for Commercial Support. Accessed on May 29, 2015.
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`FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
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`08/2015
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`FDA Blueprint for Prescriber Education for
`Extended-Release and Long-Acting Opioid Analgesics
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`Why Prescriber Education is Important
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`Health care professionals who prescribe extended-release (ER) and long-acting (LA) opioid
`analgesics (hereafter referred to as ER/LA opioid analgesics) are in a key position to balance
`the benefits of prescribing ER/LA opioid analgesics to treat pain against the risks of serious
`adverse outcomes including addiction, unintentional overdose, and death. Opioid misuse and
`abuse, resulting in injury and death, has emerged as a major public health problem.
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`•
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`• Based on the 2010 National Survey on Drug Use and Health, public health experts estimate
`more than 35 million Americans age 12 and older used an opioid analgesic for non-medical
`use some time in their life—an increase from about 30 million in 2002.3
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`In 2009, there were nearly 343,000 emergency department visits involving nonmedical use
`of opioid analgesics.4
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`In 2008, nearly 36,500 Americans died from drug poisonings, and of these, nearly 14,800
`deaths involved opioid analgesics.5
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`Improper use of any opioid can result in serious side effects including overdose and death,
`and this risk can be greater with ER/LA opioid analgesics.
`Appropriate prescribing practices and patient education are important steps to help address this
`public health problem. Health care professionals who prescribe ER/LA opioid analgesics have a
`responsibility to help ensure the safe and effective use of these drug products. ER/LA opioid
`analgesics should be prescribed only by health care professionals who are knowledgeable in
`the use of potent opioids for the management of pain.
`The expected results of the prescriber education in this REMS are that the prescribers will:
`a. Understand how to assess patients for treatment with ER/LA opioid analgesics.
`b. Be familiar with how to initiate therapy, modify dose, and discontinue use of ER/LA opioid
`analgesics.
`c. Be knowledgeable about how to manage ongoing therapy with ER/LA opioid analgesics.
`d. Know how to counsel patients and caregivers about the safe use of ER/LA opioid
`analgesics, including proper storage and disposal.
`e. Be familiar with general and product-specific drug information concerning ER/LA opioid
`analgesics.
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`I. Assessing Patients for Treatment with ER/LA Opioid Analgesic Therapy
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`a. Prescribers should consider risks involved with ER/LA opioid analgesics and balance these
`against potential benefits. Risks include:
`i. Overdose with ER/LA formulations, as most dosage units contain more opioid than
`immediate-release formulations.
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`3Substance Abuse and Mental Health Services Administration. 2011. Results from the 2010 National Survey on Drug Use and
`Health: Detailed Table, Table 7.1.a. Rockville, MD.
`http://www.samhsa.gov/data/NSDUH/2k10NSDUH/tabs/Sect7peTabs1to45.htm#Tab7.1A. Accessed on May 29, 2015.
`4Substance Abuse and Mental Health Services Administration. 2011. Drug Abuse Warning Network, 2009: National Estimates of
`Drug-Related Emergency Department Visits, Table 19. Rockville, MD.
`http://www.samhsa.gov/data/2k11/DAWN/2k9DAWNED/HTML/DAWN2k9ED.htm#Tab19. Accessed on May 29, 2015.
`5Warner M, Chen LH, Makuc DM, Anderson RN, and Miniño AM. 2011. Drug Poisoning Deaths in the United States, 1980–2008, in
`U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics,
`NCHS Data Brief, No 81. December 2011. Hyattsville, MD. http://www.cdc.gov/nchs/data/databriefs/db81.pdf. Accessed on May 29,
`2015.
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`FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
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`Life-threatening respiratory depression
`ii.
`iii. Abuse by patient or household contacts.
`iv. Misuse and addiction.
`v.
`Physical dependence and tolerance.
`vi.
`Interactions with other medications and substances (See table in Section VI for
`product-specific information).
`vii. Risk of neonatal opioid withdrawal syndrome with prolonged use during
`pregnancy.
`Inadvertent exposure/ingestion by household contacts, especially children.
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`viii.
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`b. Prescribers should assess each patient’s risk of abuse, including substance use and
`psychiatric history. Prescribers should:
`i. Obtain a complete history and conduct a complete physical examination. The
`history should include assessment for a family history of substance abuse and
`psychiatric disorders, as well as special considerations regarding dose and
`adverse effects in geriatric patients, pregnant women, and children.
`- A history of substance abuse does not prohibit treatment with ER/LA opioid
`analgesics but may require additional monitoring and expert consultation.
`ii. Be knowledgeable about risk factors for opioid abuse.
`iii. Understand and appropriately use screening tools for addiction or abuse to help
`assess potential risks associated with chronic opioid therapy and to help manage
`patients using ER/LA opioid analgesics (e.g., structured interview tools).
`iv. Adequately document all patient interactions and treatment plans.
`c. Prescribers should understand when to appropriately refer high risk patients to pain
`management specialists.
`d. Prescribers should understand opioid tolerance criteria as defined in the product labeling.
`- Prescribers should know which products and which doses are indicated for use only
`in opioid-tolerant patients. (See table in Section VI for product-specific information).
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`II. Initiating Therapy, Modifying Dosing, and Discontinuing Use of ER/LA Opioid Analgesics
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`a. Prescribers should have awareness of federal and state regulations on opioid prescribing.
`b. Prescribers should be aware that:
`i. Dose selection is critical, particularly when initiating therapy in opioid non-tolerant
`patients.
`ii. Some ER/LA opioid analgesics are only appropriate for opioid-tolerant patients.
`(See table in Section VI for product-specific information)
`iii. Dosage should be individualized in every case.
`iv.
`Titration should be based on efficacy and tolerability. (See individual product labeling)
`c. Prescribers should be knowledgeable about when and how to supplement pain
`management with immediate-release analgesics, opioids and non-opioids.
`d. Prescribers should be knowledgeable about converting patients from immediate-release to
`ER/LA opioid products and from one ER/LA opioid product to another ER/LA opioid product.
`e. Prescribers should understand the concept of incomplete cross-tolerance when converting
`patients from one opioid to another.
`f. Prescribers should understand the concepts and limitations of equianalgesic dosing and
`follow patients closely during all periods of dose adjustments.
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`FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
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`g. Prescribers should understand the warning signs and symptoms of significant respiratory
`depression from opioids and monitor patients closely, especially at the time of treatment
`initiation and dose increases.
`h. Prescribers should understand that tapering the opioid dose is necessary to safely
`discontinue treatment with ER/LA opioid analgesics when therapy is no longer needed.
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`08/2015
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`III. Managing Therapy with ER/LA Opioid Analgesics
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`ii.
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`iii.
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`a. Prescribers should establish analgesic and functional goals for therapy and periodically
`evaluate pain control, functional outcomes, side-effect frequency and intensity, and health-
`related quality of life.
`b. Prescribers should be aware of the existence of Patient Prescriber Agreements (PPAs).
`i.
`PPAs are documents signed by both prescriber and patient at the time an opioid is
`prescribed.
`PPAs can help ensure patients and caregivers understand the goals of treatment,
`the risks, and how to use the medications safely.
`PPAs can include commitments to return for follow-up visits, to comply with
`appropriate monitoring (such as random drug testing), and to safeguard the
`medication.
`c. Prescribers should monitor patient adherence to the treatment plan, especially with regard
`to misuse and abuse by:
`i. Recognizing, documenting, and addressing aberrant drug-related behavior.
`ii. Utilizing state Prescription Drug Monitoring Programs, where practical, to identify
`behaviors that may represent abuse.
`iii. Understanding the utility and interpretation of drug testing (e.g., screening and
`confirmatory tests), and using it as indicated.
`Screening and referring for substance abuse treatment as indicated.
`iv.
`Performing medication reconciliation as indicated.
`v.
`d. Prescribers should understand how to anticipate and manage adverse events associated
`with ER/LA opioid analgesics.
`e. Prescribers should be aware that there are no adequate and well-controlled studies of
`ER/LA opioid analgesics in pregnant women. ER/LA opioid analgesics should be used
`during pregnancy only if the potential benefit justifies the risk to the fetus.
`f. Prescribers should be aware of the pregnancy status of their patients. If opioid use is
`required for a prolonged period in a pregnant woman, prescribers should advise the
`patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate
`treatment will be available.
`g. Prescribers treating patients with ER/LA opioid analgesics should periodically assess
`benefits and side effects of these drugs, and the continued need for opioid analgesics.
`h. Prescribers should understand the need for reevaluation of patient’s underlying medical
`condition if the clinical presentation changes over time.
`i. Prescribers should be familiar with referral sources for the treatment of abuse or addiction
`that may arise from the use of ER/LA opioid analgesics.
`
`IV. Counseling Patients and Caregivers about the Safe Use of ER/LA Opioid Analgesics
`
`a. Prescribers should use the Patient Counseling Document as part of the discussion when
`prescribing opioid analgesics.
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`Reference ID: 3805894
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`b. Prescribers should explain product-specific information about the prescribed ER/LA opioid
`analgesic.
`c. Prescribers should explain how to take the ER/LA opioid analgesic as prescribed.
`d. Prescribers should explain the importance of adherence to dosing regimen, how to handle
`missed doses, and to contact their prescriber should pain not be controlled.
`e. Prescribers should inform patients and caregivers to read the specific ER/LA opioid
`analgesic Medication Guide they receive from the pharmacy.
`f. Prescribers should warn patients and caregivers that under no circumstances should an oral
`ER/LA opioid analgesic be broken, chewed or crushed, and patches should not be cut or
`torn prior to use, as this may lead to rapid release of the ER/LA opioid analgesic causing
`overdose and death. When a patient cannot swallow a capsule whole, prescribers should
`refer to the product labeling to determine if it is appropriate to sprinkle the contents of a
`capsule on applesauce or administer via a feeding tube.
`g. Prescribers should caution patients and caregivers that the 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. Patients and caregivers should be instructed to
`only use other CNS depressants, including other opioids, under the instruction of their
`prescriber.
`h. Prescribers should instruct patients and caregivers to tell all of their doctors about all
`medications the patient is taking.
`i. Prescribers should warn patients and caregivers not to abruptly discontinue or reduce the
`ER/LA opioid analgesic and discuss how to safely taper the dose when discontinuing.
`j. Prescribers should caution patients and caregivers that ER/LA opioid analgesics can
`cause serious side effects that can lead to death, even when used as recommended.
`Prescribers should counsel patients and caregivers on the risk factors, signs, and
`symptoms of overdose and opioid-induced respiratory depression, gastrointestinal
`obstruction, and allergic reactions.
`k. Prescribers should counsel patients and caregivers on the most common side effects of
`ER/LA opioid analgesics, and about the risk of falls, working with heavy machinery, and
`driving.
`l. Patients or caregivers should call their prescriber for information about managing side effects.
`m. Prescribers should explain to patients and caregivers that sharing ER/LA opioid
`analgesics with others may cause them to have serious side effects including death,
`and that selling or giving away ER/LA opioid analgesics is against the law.
`n. Prescribers should counsel patients and caregivers to store ER/LA opioid analgesics in
`a safe and secure place away from children, family members, household visitors, and
`pets.
`o. Prescribers should warn patients and caregivers that ER/LA opioid analgesics must be
`protected from theft.
`p. Prescribers should counsel patients and caregivers to dispose of any ER/LA opioid
`analgesics when no longer needed by flushing them down the toilet.
`q. Prescribers should counsel patients and caregivers to inform them about side effects.
`r. Adverse events should be reported to the FDA at 1-800-FDA-1088 or via
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf.
`
`
`V. General Drug Information for ER/LA Opioid Analgesic Products
`
`
`
`
`
`
`
`
`
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`Prescribers should be knowledgeable about general characteristics, toxicities, and drug
`interactions for ER/LA opioid analgesic products. For example,
`
`
`a. ER/LA opioid analgesic products are scheduled under the Controlled Substances Act and
`Reference ID: 3805894
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`FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics
`can be misused and abused.
`b. Respiratory depression is the most important serious adverse effect of opioids as it can be
`immediately life-threatening.
`c. Constipation is the most common long-term side effect and should be anticipated.
`d. Drug-drug interaction profiles vary among the products. Knowledge of particular opioid-drug
`interactions, and the underlying pharmacokinetic and pharmacodynamic mechanisms,
`allows for the safer administration of opioid analgesics.
`i. Central nervous system depressants (alcohol, sedatives, hypnotics, tranquilizers,
`tricyclic antidepressants) can have a potentiating effect on the sedation and
`respiratory depression caused by opioids.
`ii. Some ER opioid formulations may rapidly release opioid (dose dump) when exposed
`to alcohol. Some drug levels may increase without dose dumping when exposed to
`alcohol. See individual product labeling.
`iii. Using opioids with monoamine oxidase inhibitors (MAOIs) may result in possible
`increase in respiratory depression. Using certain opioids with MAOIs may cause
`serotonin syndrome.
`iv. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic
`hormone (ADH).
`Some opioids (methadon