Opioid Epidemic: FDA “Ups the Ante” on Labeling Requirements for Opioid Painkillers

March 24, 2016

On Tuesday, March 22 the FDA announced class-wide safety labeling changes for all immediate-release opioid painkillers. FDA stated that these changes are being made as part of the Agency's "continuing effort to educate prescribers and patients about the potential risks related to opioid use."

What are Opioids?

According to the FDA, "opioid analgesics are powerful pain-reducing medications that include prescription oxycodone, hydrocodone, and morphine, among others."  Prescription opioids are divided into two categories:

  1. Immediate-release (IR) products are typically prescribed for use every four to six hours and contain less of the pain-killing opioid per dose. Today, IR products account for nearly 90% of all opioids that are prescribed.
  2. Extended-release/long-acting (ER/LA) products contain more opioid per dose, which enables these products to be taken less frequently than their IR counterpart. As such, ER/LA products are generally prescribed for use only once or twice a day, depending on the individual product and patient.

Opioid Abuse Epidemic

Opioid abuse and overdose have been grown rapidly in the US, recently increasing to epidemic levels. In FDA's March 22nd press release, Commissioner Robert Califf, MD stated that "opioid addiction and overdose have reached epidemic levels over the past decade, and the FDA remains steadfast in our commitment to do our part to help reverse the devastating impact of the misuse and abuse of prescription opioids."

According to the CDC, more than 60% of all drug overdoses involve an opioid; and since 1999, the amount of prescription opioids sold in the US, as well as "the rate of overdose deaths involving opioids (including prescription opioid pain relievers and heroin)" have nearly quadrupled. Today, about 78 people die each day from an opioid overdose in the United States.

These statistics, among so many others, are the driving forces behind the FDA's recent activity and increased regulation regarding opioid medications.

Black Box Warning

FDA will now require all IR opioid medications to carry a "black box" warning concerning the serious risk of misuse, abuse, addiction, overdose, and death. This requirement is part of the Agency's overall plan focused on overcoming the current opioid abuse epidemic in the US, while still ensuring that patients in pain have adequate access to these products.

Part of the FDA's required boxed warning will include a "precaution that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening if not recognized and treated using protocols developed by neonatology experts. NOWS may occur in a newborn exposed to opioid drugs for a prolonged period while in utero."

Additional Labeling Requirements

In an effort to "inform prescribers about the importance of balancing the serious risks of opioids with their role in managing pain," FDA announced that additional safety labeling changes will be required for all prescription opioid products including supplementary information regarding the risks associated with use of these drugs.

FDA stated that because of these risks, the updated indication clarifies that the use of "IR opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options (e.g., non-opioid analgesics or opioid combination products, as appropriate) are inadequate or not tolerated." In addition, the associated dosing information includes clearer guidelines concerning drug administration and patient monitoring, including initial dosage, dosage changes during therapy, and a warning not to abruptly stop treatment in a physically dependent patient.

Furthermore, FDA will mandate all opioid products to update their labelling "to include safety information about potentially harmful drug interactions with other medicines that can result in a serious central nervous system condition called serotonin syndrome. Updated labeling will also include information about opioid effects on the endocrine system, including a rare but serious disorder of the adrenal glands (called adrenal insufficiency) and decreased sex hormone levels (androgen deficiency). These labeling changes will also make it clear that these negative outcomes can occur whether a patient is taking an opioid to treat pain or if the product is being used for MAT."

For additional information on FDA's opioid labeling requirements, view the Agency's press release and associated information, including:

Do you manufacture an opioid medication, controlled substance, or other FDA-regulated product? We can help ensure that your product is compliant with all FDA requirements. For more information on our services, contact us today.


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