The Food and Drug Administration ( FDA ) has announced class-wide safety labeling changes and new postmarket study requirements for all extended-release and long-acting ( ER/LA ) opioid analgesics intended to treat pain.

The updated indication states 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 updated indication further clarifies 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.

Recognizing that more information is needed to assess the serious risks associated with long-term use of ER/LA opioids, the FDA is requiring the drug companies that make these products to conduct further studies and clinical trials. The goals of these postmarket requirements are to further assess the known serious risks of misuse, abuse, increased sensitivity to pain ( hyperalgesia ), addiction, overdose, and death.

The FDA is also requiring a new boxed warning on ER/LA opioid analgesics to caution that chronic maternal use of these products during pregnancy can result in neonatal opioid withdrawal syndrome ( NOWS ), which may be life-threatening and require management according to protocols developed by neonatology experts. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

In addition, the FDA is notifying ER/LA opioid analgesic application holders of the need for changes to the following sections of drug labeling: Dosage and Administration; Warnings and Precautions; Drug Interactions; Use in Specific Populations; Patient Counseling Information, and the Medication Guide.

Once the safety labeling changes are finalized, modifications will also be made to the ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy ( REMS ), to reflect the updated information.
Originally approved in 2012, the ER/LA Opioid Analgesics REMS requires companies to make available to health care professionals educational programs on how to safely prescribe ER/LA opioid analgesics and to provide Medication Guides and patient counseling documents containing information on the safe use, storage, and disposal of ER/ LA opioids.

In addition to the safety labeling changes and postmarket study requirements, the FDA has issued responses to two related citizen petitions. ( Xagena )

Source: FDA, 2013

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