Risk Evaluation and Mitigation Strategy Compliance
On July 9, 2012, the Food and Drug Administration (FDA) announced a risk evaluation and mitigation strategy (REMS) for long-acting (LA) opioid products.1 The new REMS will affect nearly 20 manufacturers and more than 20 LA and extended-release (ER) opioid products. Although these medications are FDA-approved for chronic moderate-to-severe pain management, these products have been linked to reports of abuse, misuse, harm, and even deaths. According to the most recent Drug Abuse Warning Network (DAWN) Report from July 2012, there were approximately 2.3 million emergency department (ED) visits related to drug misuse or abuse in 2010, with more than 650,000 of these visits related to pain relievers.2 The majority of these ED visits were associated with the abuse or misuse of opioid pain relievers, with hydrocodone and oxycodone products accounting for the bulk of these visits.
In response to this growing problem, the White House’s Prescription Drug Abuse Prevention Plan from 2011 included a recommendation for the development of an opioid REMS aimed at improving safe prescribing practices for these products.3 Within the Prevention Plan, one of the goals was to have an approved and implemented REMS for certain LA/ER opioids within 12 months. This new LA/ER opioid REMS satisfied this goal and includes voluntary prescriber training on all LA/ER opioid analgesics (Table 1), access to a Patient Counseling Document (PCD) for these products, and a unique medication guide for each product that will be given to patients at the time of dispensing.1,4,5
According to the FDA, voluntary training for the some 320,000 LA/ER opioid prescribers is a way to curb misuse and abuse without being overly burdensome.6 The continuing education (CE) activities of the new REMS are aimed at including 3 hours of core content focusing on safe prescribing of LA/ER opioid products. The content, while directed at prescribers, will also be relevant for other health care providers such as pharmacists and nurses. The key elements of the prescriber training are briefly outlined here and are described in more detail in Table 2.
Assessment and Patient Selection
Since the implementation of this REMS is intended to help curb opioid abuse and misuse, prescribers are expected to assess patients’ risks of abuse prior to initiation of LA/ER opioid therapy. Therefore, prescribers need education on the proper assessment of patients including substance use disorder screening.6 There are several screening and assessment tools available to assist in this process.7-11 Tools that may be considered for use include the Screener and Opioid Assessment for Patients with Pain (SOAPP) Version 1, the Revised SOAPP (SOAPP-R), the Opioid Risk Tool (ORT), and the Diagnosis, Intractability, Risk, and Efficacy (DIRE) instrument. The SOAPP, SOAPP-R, and ORT are completed by patients, whereas the DIRE is completed by the clinician. These risk assessment tools for aberrant behavior have been preliminarily validated in several studies and are endorsed by the American Pain Society-American Academy of Pain Medicine.7-12 They can be found in the clinical guidelines for the use of chronic opioid therapy in patients with chronic noncancer pain, and some tools are available online at www.opioidrisk.com.12
Managing and Monitoring
Prescribers should also be educated on initiation, modification, and discontinuation of therapy.6 Some of the LA/ER opioid products differentiate between appropriate use in opioid-tolerant patients, those previously exposed to opioid therapy, and opioid non-tolerant patients. For example, the buprenorphine transdermal systems (Butrans) at doses of 10 mcg/hr and 20 mcg/hr should only be used in opioid-tolerant patients. In addition, single doses of oxycodone controlled-release tablets >40 mg or total daily doses >80 mg are to be used only in opioid-tolerant patients as well. Prescribers should also be familiar with how and when to supplement patients with immediate-release analgesic preparations, and how to convert patients from immediate-release preparations to LA/ER products or from one LA/ER product to another. Some specific dosing information for the LA/ER products is summarized in Table 3.
Prescribers must also be knowledgeable of appropriate titration and tapering schedules in order to avoid overdose or withdrawal symptoms in patients. Signs and symptoms of opioid intoxication include miosis, excessive sedation, respiratory depression, hypotension, urinary retention, bradycardia, and/or altered mental status.13 These effects may be life threatening, especially in combination with other central nervous system (CNS) depressants. Conversely, opioid withdrawal, which includes symptoms such as anxiety, malaise, diaphoresis, mydriasis, tremors, gastrointestinal distress, and piloerection, may occur as a result of rapid or abrupt discontinuation of therapy. Tapering schedules generally include reductions of opioid doses every few days or weekly.12
Routine monitoring should involve repeated evaluations and documentation of pain severity and progress to therapeutic goals.12 Monitoring of functional ability and adverse events should be part of this monitoring, as well as checking for aberrant drug-related behaviors. This can be achieved by pill counts, family interviews, urine toxicology screening, or through use of the Pain Assessment and Documentation Tool (PADT) or Current Opioid Misuse Measure (COMM) available online at www.opioidrisk.com.
Implementation and Awareness
Dissemination of educational materials will be achieved through a variety of methods, including a Web site (www.er-la-opioidrems.com), which contains a current list of training as it becomes available, a copy of the PCD and FDA-approved medication guides, and copies of prescriber letters.6 These letters were sent by the manufacturers to all Drug Enforcement Agency-registered prescribers of Schedule II and III drugs, and will serve to alert the prescribers of the new REMS and to notify them of upcoming accredited CE courses once they are created. Similar documents were also sent to professional organizations and licensing boards. Although the prescriber training is voluntary, the FDA expects that 25% of prescribers will be compliant with the REMS training within 2 years from the time the first REMS-compliant training is made available. After 3 years, the FDA expects 50% compliance and at 4 years, 60% compliance. The FDA anticipates the first CE activities to be offered by March 1, 2013. The education will be funded by independent educational grants from the manufacturers of the affected opioid products.