Opioid REMS Update 2013

When we last covered the topic of the FDA’s intended plans for curbing opioid risk, we felt confident that one thing was for sure – education would likely be a key ingredient of the ultimate implemented solution. As it turns out, our assumption was correct.

As we mentioned in our opioid REMS update 2012, on Tuesday, April 19th, 2011, a press conference was held to announce the White House’s National Prescription Drug Abuse Action Plan. The plan underscored the national “crisis” that exists with respect to abuse, misuse, and unintended deaths resulting from prescription pain medications. This plan would involve a number of different governmental agencies working in concert to battle the problem.

This national plan would have a 4-pronged approach to battling the crisis surrounding abuse, misuse, inappropriate prescribing, and diversion of prescription pain medications:

  • Education
    • Pharmaceutical manufacturers will be required to fund educational initiatives about safe and appropriate use devoted to both health care providers and patients
  • Monitoring
    • Implementation of prescription monitoring programs across all of the United States
  • Disposal
    • Issues surrounding drug disposal and drug “take-back” programs need to made more available, and consistent
  • Enforcement
    • “Pill mills” and other healthcare providers that are contributing to the problem through illegal or unethical practices need to be brought to justice, and shut down

A major component of this national plan was announced at this press conference by Dr. Margaret Hamburg, Commissioner of the Food and Drug Administration (FDA). Dr Hamburg announced the implementation of a Risk Evaluation and Mitigation Strategy (REMS) that would now apply to allprescription long-acting and extended-release opioid medications. Dr. Hamburg underscored the value of opioid medications, but also pointed out the risk, and apparent failure of prior educational efforts and initiatives to mitigate risk. She said that, “Despite these prior efforts, the incidence of abuse, misuse, and accidental overdose are on the rise.”

Dr. Hamburg also stated that the purpose of the opioid REMS is, “To ensure that health professionals have the knowledge and training to deliver effective pain management and care and that patients understand the risks involved with these medications,” and described the implementation of the opioid REMS and its framework:

  • As part of the REMS, manufacturers of these opioid formulations would be required to develop risk management plans that take risk/benefit into consideration for this entire class of medications
  • Educational materials and programs would need to be developed that specifically target healthcare professionals and patients
    • Two key features of these materials were identified:
      • – Medication guides to help patients understand benefits and risks
      • – Rigorous education for healthcare professionals who prescribe these medications

All companies that make extended-release/long-acting opioids were asked by the FDA to work collaboratively to create a single, shared, broad-application REMS program that would encompass all medications in this class. Although individual medications have been required to submit a REMS as part of their application, or to implement one post-FDA approval, this was the first time that the FDA had indicated that a REMS will be needed on a “class-wide” basis. The likely impetus is the number of drug-related deaths associated with extended-release and long-acting opioids.

The opioid REMS would emphasize education of prescribers, stating that, “Health care professionals who prescribe extended-release (ER) and long-acting (LA) opioids are in a key position to balance the benefits of prescribing ER/LA opioids 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.”

On November 4th, 2011, the FDA released a draft blueprint for the educational component of the opioid REMS, with “the prescriber training to be conducted by accredited, independent continuing education (CE) providers, with little or no cost to the healthcare professionals, under unrestricted grants to accredited CE providers funded by the sponsors.”

The draft blueprint outlined five major subject areas of education that would facilitate a prescriber’s ability to:

  1. 1. Understand how to assess patients for treatment with ER/LA opioids
    • – Give consideration to risks involved with ER/LA opioids and balance these against potential benefits
      • Risks of concern include:
        • – Overdose due to the high dosage of opioid available as an ER/LA formulation
        • – Intentional abuse by patient or household contacts
        • – Addiction
        • – Interactions with other medications and substances
        • – Inadvertent exposure to household contacts (e.g., children)
  2. 2. Be familiar with how to initiate therapy, modify dose, and discontinue use of ER/LA opioids, including specific attention to:
    • Awareness of federal and state regulations
    • – Consideration that dose selection is critical
    • – Knowledge about conversion from IR to ER/LA, and from one ER/LA to another
    • – Issues surrounding opioid cross-tolerance
    • Equianalgesic dosing concepts and monitoring
    • – Necessity for tapering when decision is exit strategy
  3. 3. Be knowledgeable about how to manage ongoing therapy with ER/LA opioids
    • – Clear establishment of goals of treatment
      • – Regular re-evaluation for pain, function, and QOL
    • – Use of Patient-Provider Agreements (PPAs)
      • Not mandated, but recommended
    • – Assurance that patients are adherent to treatment plan
    • Monitor patients for aberrant behaviors:
      • – Awareness
      • – Interview
      • – Prescription Drug Monitoring Programs (PDMPs)
      • – Screening for substance abuse/behaviors (e.g., SOAPP, ORT)
      • – Understand the role of drug-screening (e.g., UDS)
      • – Medication reconciliation at each visit
    • – Management of adverse effects
    • – Re-assessment of efficacy and tolerance
    • – Re-assessment of appropriateness of continuation of chronic opioid therapy
    • – Re-assessment of underlying pain condition
  4. 4. Know how to counsel patients and caregivers about the safe use of ER/LA opioids, including:
    • Product-specific information about the specific opioid prescribed
    • – General directions for safe and appropriate use
    • Explicit warning against modification of formulation (e.g., crushing, chewing)
    • – Caution about use of other CNS depressants concomitantly, including alcohol
    • – Symptoms of withdrawal
    • – Warning about legal aspects and dangers of sharing prescription medications
    • – Safe storage
    • – Disposal
    • – Adverse effects
  5. 5. Be familiar with general and product specific drug information concerning ER/LA opioids
    • – General characteristics of ER/LA formulations
    • – Toxicity
    • – Drug interactions
    • – Examples of adverse effects, including:
      • – Respiratory depression
      • – Constipation
      • – Drug-drug interactions
    • – Tolerance
    • – Specifics about formulation (e.g. oral, transdermal)
    • – Knowledge related to the specific molecule
      • – Dose form/strength
      • – Dosing interval
      • – “Key” instructions to convey to patients
      • – Major drug interactions
      • – Use in opioid-tolerant vs. experienced patients
      • – Drug-specific adverse events
    • – Morphine equivalency

On July 9th 2012, the final version of the FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics was released, mandating that as part of the REMS, all manufacturers of ER/LA opioid analgesics must provide:

  • Education for prescribers of these medications, which will be provided through accredited continuing education (CE) activities supported by independent educational grants from ER/LA analgesic companies
    • 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 (are posted at www.ER-LA-opioidREMS.com as that information becomes available)
  • Information that prescribers can use when counseling patients about the risks and benefits of ER/LA opioid analgesic use

On September 10, 2013, the FDA announced new labeling changes and post-market study requirements for ER/LA opioid analgesics. Dr. Hamburg stated that ”The FDA is invoking its authority to require safety labeling changes and post-market studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities. Today’s action demonstrates the FDA’s resolve to reduce the serious risks of long-acting and extended release opioids while still seeking to preserve appropriate access for those patients who rely on these medications to manage their pain.” Once the safety labeling changes are finalized, the FDA stated that modifications will also be made to the ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS), to reflect the updated information.

From our perspective at PainEDU.org, it is always all about education of stakeholders, and ultimately all about the patient, and their best interests. The challenge will be to ensure access to patients in need that are appropriate candidates for extended-release opioids, while achieving the desired goals. As always, stay tuned; we will shortly have more information to share about our upcoming role in opioid REMS education.