FDA Strengthens Warnings for Immediate-Release Opioid Pain Medications

Immediate-release formulations get safety labeling changes

The FDA has announced required class-wide safety labeling changes for immediate-release (IR) opioid pain medications. Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse, abuse, addiction, overdose, and death. The agency is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on the risk of these medications.

Opioid analgesics are powerful pain-reducing medications that include prescription oxycodone, hydrocodone, and morphine. Prescription opioids are divided into two main categories: IR products, which are usually intended for use every four to six hours, and extended-release/long-acting (ER/LA) products, which are primarily intended to be taken once or twice a day, depending on the individual product and patient. Certain opioids, such as methadone and buprenorphine, are also used to treat opioid addiction, and when used in combination with behavioral therapy and counseling, they are known as medication-assisted treatment (MAT).

The updated indication clarifies that because of these risks, IR opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options (e.g., nonopioid analgesics or opioid combination products, as appropriate) are inadequate or not tolerated. The dosing information also provides clearer instructions regarding patient monitoring and drug administration, including initial dosage, dosage changes during therapy, and a warning not to abruptly stop treatment in a physically dependent patient.

As part of the boxed warning on IR opioid analgesics, the FDA now requires 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 in utero.

In 2013, the FDA required class-wide labeling changes for ER/LA opioid analgesics that included modifications to the products’ indications, limitations of use, and warnings, including boxed warnings to communicate more effectively to prescribers the serious risks associated with these drugs. The FDA is now requiring similar changes to the labeling of IR opioid analgesics.

In addition, the FDA is requiring updated labeling for all opioids (both ER/LA and IR products) to include safety information about potentially harmful drug interactions with other medications that can result in a serious central nervous system condition known as serotonin syndrome. Updated labeling will also include information about the effects of opioids on the endocrine system, including adrenal insufficiency and androgen deficiency. These labeling changes will also make it clear that these negative outcomes can occur regardless of whether a patient is taking an opioid to treat pain or the product is being used for MAT.

Source: FDA; March 22, 2016.