New FDA Safety Warnings on Immediate-Release Opioids

Megan Brooks


March 22, 2016

The US Food and Drug Administration (FDA) today announced new class-wide safety labeling changes for immediate-release (IR) opioid pain medications, which make up about 90% of all opioid prescriptions.

The new labels include a new boxed warning about the risks for misuse, abuse, addiction, overdose and death.

In addition, as they did in 2013 with extended-release/long-acting (ER/LA) opioid products, the FDA said today IR opioid products are indicated not for merely moderate pain but rather only for the management of pain severe enough to require opioid treatment and for which alternative treatments are inadequate.

That's "a substantial change" for these products, Douglas Throckmorton, MD, deputy center director of regulatory programs, FDA Center for Drug Evaluation and Research, said during a media briefing.

"In 2013, the FDA had concerns about the disproportionate risks of ER/LA analgesics. First, many ER/LA analgesics contain more active ingredient per tablet than IR analgesics and have an increased risk of overdose and death on a per tablet basis," Dr Throckmorton explained.

"Additionally, the long-acting nature of ER/LA opioid analgesics meant that ER/LA patients who suffered negative consequences from their use such as depressed breathing associated with an overdose would be in danger for longer periods of time than IR patients," he said. Further, ER/LA products were more attractive for abusers.

"Today, the FDA is requiring similar changes to the labeling of IR opioid analgesics," the agency said in the release.

The dosing information on the new IR labels 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, the FDA said.

As part of the new boxed warning on IR opioid analgesics, the FDA now requires a precaution that long-term maternal use of opioids during pregnancy can lead to neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.

"We are also working to improve the information available to patients by requiring medication guides to help them avoid serious adverse effects of IR opioids," Dr Throckmorton said.

The FDA is also requiring several additional safety labeling changes across all prescription opioid products (both ER/LA and IR products) to include additional information on potential risk with these medications. In particular, the labels will cite potentially harmful drug interactions with other drugs that can lead to serotonin syndrome. Updated labeling will also include information about opioid effects on the endocrine system, including adrenal insufficiency and androgen deficiency.

The potential risks are outlined in a Drug Safety Communication posted today on the FDA website.

"The broad set of actions announced today is reflective of the FDA's efforts to improve informed prescribing of opioids across the board," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in the release. "We have been and will continue to evaluate all new data to ensure that labels of opioid drugs contain appropriate prescribing information about the benefits and risks of prescription opioids."

A Plea to Prescribers

FDA Commissioner Robert Califf, MD, told reporters, "While the FDA alone can't solve this crisis, we are committed to working in partnership with other government agencies, healthcare providers, medical products industry and most importantly patients and their families to prevent abuse, save lives and treat dependence while still providing patients in pain access to effective relief."

He added, "Many us here at the FDA are physicians. We've dedicated our careers to the treatment and care of patients and we understand the challenges that many physicians face when determining treatment for patients in pain. We're at a time where the unfathomable tragedies from addiction, overdose and death has become one of the most urgent and devastating public health crises facing our country.

It's our hope and really our plea that the changes that we've announced today will help physicians make more informed decisions about prescribed opioids to patients in pain. Dr Robert Califf

"While there is not one cause and there will be no one single solution to this issue, I can't stress enough how critical it is for prescribers to have the most current information about potential risks these products pose," he said.

"It's our hope and really our plea that the changes that we've announced today will help physicians make more informed decisions about prescribed opioids to patients in pain," Dr Califf said.

The FDA also announced today that it is 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, the FDA will take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications," the agency said.


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