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Regulatory Focus™ > News Articles > FDA Requires New Labels for Opioids

FDA Requires New Labels for Opioids

Posted 22 March 2016 | By Zachary Brennan 

FDA Requires New Labels for Opioids

The US Food and Drug Administration (FDA) on Tuesday announced class-wide safety labeling changes for immediate-release (IR) opioid pain medications, which make up about 90% of all opioid prescriptions. The labels now include a new boxed warning about the serious risks of misuse, abuse, addiction, overdose and death.

FDA is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on their risks, which is part of a wider FDA effort first announced last month to balance these risks with their role in managing pain.

The labeling changes come as the US battles an opioid epidemic, with more than 28,000 people killed by opioids in 2014, which is more than any year on record. At least half of all opioid overdose deaths involve a prescription opioid, according to the Centers for Disease Control and Prevention. Earlier this month, the Senate passed a bill that would offer local communities hundreds of millions to help battle the epidemic. An identical bill is moving through the House.

Prescription opioids are divided into two main categories – IR products, 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. Certain opioids, such as methadone and buprenorphine, are also used as a form of treatment for opioid addiction, or medication-assisted treatment (MAT).

FDA said in a conference call Tuesday that when finalized, the new boxed warnings will be added to 87 innovator and 141 generic IR opioids. The agency also said it's still considering whether to add a risk evaluation and mitigation strategy (REMS) for IR opioids, which is already used for ER/LA opioids.

New Labels

The updated label clarifies that because of the risks, 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.

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, FDA also now requires a warning that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which FDA says 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.

“We know that there is persistent abuse, addiction, overdose mortality and risk of NOWS associated with IR opioid products,” said Douglas Throckmorton, deputy center director of regulatory programs at FDA’s Center for Drug Evaluation and Research.

Additionally, 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 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 (known as adrenal insufficiency) and decreased sex hormone levels (androgen deficiency). These labeling changes will also clarify 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.

FDA Commissioner Robert Califf said in a statement: “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.”

FDA also said it’s aware of, and carefully reviewing, available scientific information about potentially serious outcomes related to interactions between benzodiazepines and opioids. Once a review of all available scientific information is completed, FDA says it will take necessary actions to ensure prescribers and the public are informed of the risks involved.

The agency, meanwhile, also released Tuesday its denial of opioid manufacturer Purdue Pharma's petition to demonstrate that IR opioids have similar risks as ER/LA opioids. 

The updated labels come as in 2013, 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 more effectively communicate to prescribers the serious risks associated with these drugs.

New Safety Measures Announced for Immediate Release (IR) Opioids

March 22, 2016, Required Safety Labeling Language for Immediate-Release Opioids

FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes

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