On September 10, 2013, the Food and Drug Administration (FDA) announced a number of changes that are intended to increase the safety of extended-release and long-acting (ER/LA) opioid medications. This announcement applies to all currently marketed ER/LA opioids, and implements two specific approaches to achieve the goal of combatting “the crisis of misuse, abuse, addiction, overdose, and death” according to Margaret Hamburg, MD, Commissioner of FDA. These measures are intended to compliment the implementation of the ER/LA opioid Risk Evaluation and Mitigation Strategy (REMS) approved by and mandated by the FDA in 2012.
The additional approaches include:
- 1. Class-wide labeling changes for ER/LA opioid medications
- 2. Further studies and clinical trials of already approved ER/LA opioids to further assess the risks of aberrant behaviors, opioid-induced sensitivity to pain (hyperalgesia), overdose, and death beyond the scope of past research
The label changes will include new language that is intended to facilitate further stratification and appropriate patient selection by healthcare providers that prescribe ER/LA opioid medications. Changes will be made to the indications section of all ER/LA opioid labels to state that “ER/LA opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.” The label changes will also further clarify that “because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; ER/LA opioid analgesics are not indicated for as-needed pain relief.”
Additionally, the FDA is also requiring a new, boxed-warning in labels to warn prescribers about risk of aberrant behaviors, overdose, and death; the importance of adequate assessment and monitoring; the risk of respiratory depression related to initiation of therapy, dose increases, and disruption of formulation; accidental exposure to children leading to overdose; and chronic maternal use leading to neonatal abstinence syndrome (NAS); a serious problem that has become significant in many areas across the country.
The FDA has also made requirements for changing the sections of the ER/LA labels that address:
- – Dosage and administration
- – Warnings and precautions
- – Drug interactions
- – Use in specific populations
- – Patient counseling information
- – The medication guide
Highlights of the further studies and clinical trials required by the FDA are that they attempt to address the following aims related to aberrant behaviors, overdose, and death:
- – Estimating the incidence associated with chronic use of opioid analgesic therapy
- – Evaluating and quantifying additional risk factors
The timeline requirements for these studies are that protocols need to be submitted to the FDA by August 2014 and completed by January 2018. The FDA recommended that these studies capture all opioid use among populations studied, rather than specific products. Additionally, a study investigating the development of opioid-induced hyperalgesia and tolerance is required to help better determine risk relative to efficacy.