FDA requires warning on opioids

A month after FDA announced several measures aimed at curbing opioid abuse, the agency said it would require a new boxed warning addressing the serious risk of misuse, abuse, addiction, overdose and death on immediate-release (IR) opioid pain medications.

FDA is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on the risk of IR opioids.

Related: FDA makes sweeping changes for opioids

The sweeping actions, announced on March 22, modify the approved indications for use of medications, and add boxed warnings, in many cases. “Until this action, very few IR products had boxed warnings,” Doug Throckmorton, MD, deputy center director of regulatory programs for FDA’s Center for Drug Evaluation and Research (CDER), said on a phone call with reporters.

Boxed warnings will include statements cautioning that addiction can occur even when opioids are used at appropriate levels, Thockmorton said.

“Today’s actions are one of the largest undertakings for informing prescribers of risks across opioid products, and one of many steps the FDA intends to take this year as part of our comprehensive action plan to reverse this epidemic,” said Robert Califf, MD, the new FDA commissioner.

A boxed warning on interactions between benzodiazepines and opioids could be forthcoming, as FDA is “aware of, and carefully reviewing, available scientific information about potentially serious outcomes related to interactions between benzodiazepines and opioids”, the agency said in a statement. “Once a review of all available scientific information is completed, FDA will take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications,” the statement said.

Related: Drop in opioid Rx, overdoses linked to pharmacy changes

 The updated boxed warning clarifies that, because of the associated risks, IR opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options (such as non-opioid analgesics or opioid combination products, as appropriate) are inadequate or not tolerated.

The new 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.

“FDA is committed to working with the healthcare community to help avoid opioid abuse and misuse, while assuring that patients have appropriate access to pain medications,” Thockmorton said.

FDA also now requires a precaution in the boxed warning 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,” FDA said.

Additionally, 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 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). 

Read more: Top 4 new prescription opioid abuse facts