In September 2013, the U.S. Food and Drug Administration (FDA) announced labeling changes and additional study/clinical trial requirements for extended-release (ER) and long-acting (LA) opioid analgesics used to treat pain.

These drugs include long-term versions of morphine, oxycodone, fentanyl, and others. The FDA based its revisions on a thorough analysis of safety information, the review of several relevant medical publications, and input from patients, experts, and medical professionals.

Labeling Changes

Extended-release and long-acting opioids, which are available by prescription and come in several forms—pills, liquids, skin patches—often contain higher doses of medication than immediate-release opioids and opioid/non-opioid combination drugs. Because these medications can pose significant risks and safety concerns, new label requirements will stress that other treatment options should be considered before ER/LA opioid drugs.

According to the FDA, the indications on labels will change from, "...the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time," to, "...the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate."

The "limitations of use" portion of the new label will continue to state that ER/LA opioids are not intended to be used "as needed." Revised labeling also will indicate that:

    "Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formations, reserve [these medications] for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain."

According to the updated recommendations, patients should undergo a thorough evaluation that includes a pain rating scale assessment, as well as a professional determination that alternative treatments are ineffective and their pain requires constant, long-term opioid medications. Health care providers should evaluate each person's pain along with his or her ability to perform daily tasks and live a reasonably good quality of life.

New labeling will also provide more information about the dangers of using opioid pain medications during pregnancy, labor, and nursing. A Boxed Warning will caution about the effects of opioids on newborns—neonatal opioid withdrawal syndrome (NOWS).

NOWS can cause the following:

  • Excessive or high-pitched crying
  • Poor feeding
  • Rapid breathing
  • Trembling

Additional Studies

More information is needed to determine the benefits and risks of long-term use of ER/LA opioids. New FDA regulations require drug manufacturers to conduct studies and clinical trials to evaluate long-term use and assess potential risks like increased sensitivity to pain, misuse, abuse, addiction, overdose, and death.

In addition to the revised labeling, the FDA reports that educational materials for patients, pharmacists, and health care providers—including a handout given to patients when they fill their extended-release or long-acting opioid pain medication prescription—will also be updated.

Revisions will also be made to the ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS). The REMS requires the manufacturers of these drugs to provide continuing education classes about ER/LA opioid risks and safety to health care providers who prescribe them.

In October 2013, the FDA approved the first extended-release, single-entitiy hydrocodone (hydrocodone bitartrate extended-release capsules; Zohydro ER). Like for other ER/LA opioids, additional post-marketing studies—to determine risks for misuse, abuse, addiction, overdose, and other associated complications—are being required by the Food and Drug Administration. Prolonged use of Zohydro ER during pregnancy can cause opioid withdrawal syndrome in the newborn, which can be life-threatening.

Targiniq ER (oxycodone hydrochloride and naloxone hydrochloride extended release tablets) was approved in July 2014 for severe pain that requires daily, long-term treatment and does not respond to other treatment options. Targiniq ER has abuse-deterrent properties—when the medication is crushed (for injection or to be snorted), the naloxone blocks the euphoric effects of the oxycodone. However, overdose—taking too much of the medication orally, either on purpose or by accident—is still possible.

Common side effects of the drug include nausea and vomiting. According to the FDA, more studies are being conducted to assess the risk for abuse and the abuse-deterrent features of the medication.

Labeling changes were approved by the FDA in October 2014 for morphine sulfate and naltrexone hydrochloride (Embeda) extended-release (ER) capsules. Embeda has properties similar to Targiniq that are expected to reduce (not eliminate) abuse of the drug when it is crushed.

Source: U.S. Food and Drug Administration (FDA); Updated by Remedy Health Media

Publication Review By: the Editorial Staff at

Published: 12 Sep 2013

Last Modified: 21 Oct 2014