FDA announces classwide label changes to extended-release/long-acting opioids

The U.S. Food and Drug Administration has announced that it is making classwide label changes to extended-release and long-acting opioid analgesics for treatment of chronic pain. In addition, drug manufacturers will now be required to conduct postmarket studies to help the agency determine whether further actions are merited.

"The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities," Dr. Margaret A. Hamburg, FDA commissioner, said Sept. 10 in a press briefing. "Today’s action demonstrates the FDA’s resolve to reduce the serious risks of long-acting and extended release opioids while still seeking to preserve appropriate access for those patients who rely on these medications to manage their pain."

Extended-release and long-acting opioids include hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol. Changes to labels will include updated information about dosage and administration, warnings and precautions, drug interactions, use in specific populations, patient counseling information, and the medication guide. Modifications also will be made to the extended-release/long-acting opioid analgesics Risk Evaluation and Mitigation Strategy (REMS), to reflect the updated information.

The key change centers on moving prescribers away from the assessment of a patient’s pain based solely on a pain scale to a more "comprehensive one," according to Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research. "The updated indication states that extended-release, long-acting opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate," Dr. Throckmorton stated in the briefing. Alternative pain medications noted in an agency statement released prior to the briefing include immediate-release opioids, which are currently unaffected by the agency’s labeling changes.

Dr. Throckmorton said he hopes the FDA’s action is part of a "broader effort to encourage people to consider how best to use these medications." When asked whether prescribers and their patients weren’t already addressing the risks and benefits involved in the use of these opioids, the current labeling for which indicates their use in patients experiencing "moderate to severe pain," rather than "round-the-clock" pain, Dr. Throckmorton said the labeling changes "will help reinforce the importance of the conversation in a busy practice."

The agency’s announcement comes amid growing data about the inherent risks of opioid use reported in the medical literature and the filing with the FDA of two citizen petitions to change how opioids are prescribed, including one by the Physicians for Responsible Opioid Prescribing. Also part of the focus on opioid use is the 19 to 10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January to reschedule hydrocodone drug combinations from schedule III under the Controlled Substances Act (CSA) to schedule II. The vote was prompted by the U.S. Drug Enforcement Administration’s call for the FDA to react to evidence that the medications are overprescribed, diverted, and abused. Statistics cited by FDA officials in the briefing included nearly 16,000 opioid-related deaths in the United States in 2009, reflecting a 300% increase in the last 20 years.

Speaking about the importance of the dosage and duration of the medications, Dr. Throckmorton said the agency did not have enough information at this time to make changes to how these drugs are prescribed, but that the postmarket studies such as clinical trials, and other studies of at least 12 weeks’ duration, would play a role in providing this data. "We expect some of those studies will provide information for us to use in 2 years. So, by end of 2015, we will have more," Dr. Throckmorton said.

Also announced in the briefing was the addition of a boxed warning on extended-release/long-acting opioid analgesics to warn expectant mothers of neonatal opioid withdrawal syndrome (NOWS), which might be life-threatening and require management according to protocols developed by neonatology experts. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

The U.S. Food and Drug Administration has announced that it is making classwide label changes to extended-release and long-acting opioid analgesics for treatment of chronic pain. In addition, drug manufacturers will now be required to conduct postmarket studies to help the agency determine whether further actions are merited.

"The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities," Dr. Margaret A. Hamburg, FDA commissioner, said Sept. 10 in a press briefing. "Today’s action demonstrates the FDA’s resolve to reduce the serious risks of long-acting and extended release opioids while still seeking to preserve appropriate access for those patients who rely on these medications to manage their pain."

Extended-release and long-acting opioids include hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol. Changes to labels will include updated information about dosage and administration, warnings and precautions, drug interactions, use in specific populations, patient counseling information, and the medication guide. Modifications also will be made to the extended-release/long-acting opioid analgesics Risk Evaluation and Mitigation Strategy (REMS), to reflect the updated information.

The key change centers on moving prescribers away from the assessment of a patient’s pain based solely on a pain scale to a more "comprehensive one," according to Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research. "The updated indication states that extended-release, long-acting opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate," Dr. Throckmorton stated in the briefing. Alternative pain medications noted in an agency statement released prior to the briefing include immediate-release opioids, which are currently unaffected by the agency’s labeling changes.

Dr. Throckmorton said he hopes the FDA’s action is part of a "broader effort to encourage people to consider how best to use these medications." When asked whether prescribers and their patients weren’t already addressing the risks and benefits involved in the use of these opioids, the current labeling for which indicates their use in patients experiencing "moderate to severe pain," rather than "round-the-clock" pain, Dr. Throckmorton said the labeling changes "will help reinforce the importance of the conversation in a busy practice."

The agency’s announcement comes amid growing data about the inherent risks of opioid use reported in the medical literature and the filing with the FDA of two citizen petitions to change how opioids are prescribed, including one by the Physicians for Responsible Opioid Prescribing. Also part of the focus on opioid use is the 19 to 10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January to reschedule hydrocodone drug combinations from schedule III under the Controlled Substances Act (CSA) to schedule II. The vote was prompted by the U.S. Drug Enforcement Administration’s call for the FDA to react to evidence that the medications are overprescribed, diverted, and abused. Statistics cited by FDA officials in the briefing included nearly 16,000 opioid-related deaths in the United States in 2009, reflecting a 300% increase in the last 20 years.

Speaking about the importance of the dosage and duration of the medications, Dr. Throckmorton said the agency did not have enough information at this time to make changes to how these drugs are prescribed, but that the postmarket studies such as clinical trials, and other studies of at least 12 weeks’ duration, would play a role in providing this data. "We expect some of those studies will provide information for us to use in 2 years. So, by end of 2015, we will have more," Dr. Throckmorton said.

Also announced in the briefing was the addition of a boxed warning on extended-release/long-acting opioid analgesics to warn expectant mothers of neonatal opioid withdrawal syndrome (NOWS), which might be life-threatening and require management according to protocols developed by neonatology experts. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

The U.S. Food and Drug Administration has announced that it is making classwide label changes to extended-release and long-acting opioid analgesics for treatment of chronic pain. In addition, drug manufacturers will now be required to conduct postmarket studies to help the agency determine whether further actions are merited.

"The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities," Dr. Margaret A. Hamburg, FDA commissioner, said Sept. 10 in a press briefing. "Today’s action demonstrates the FDA’s resolve to reduce the serious risks of long-acting and extended release opioids while still seeking to preserve appropriate access for those patients who rely on these medications to manage their pain."

Extended-release and long-acting opioids include hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol. Changes to labels will include updated information about dosage and administration, warnings and precautions, drug interactions, use in specific populations, patient counseling information, and the medication guide. Modifications also will be made to the extended-release/long-acting opioid analgesics Risk Evaluation and Mitigation Strategy (REMS), to reflect the updated information.

The key change centers on moving prescribers away from the assessment of a patient’s pain based solely on a pain scale to a more "comprehensive one," according to Dr. Douglas Throckmorton, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research. "The updated indication states that extended-release, long-acting opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate," Dr. Throckmorton stated in the briefing. Alternative pain medications noted in an agency statement released prior to the briefing include immediate-release opioids, which are currently unaffected by the agency’s labeling changes.

Dr. Throckmorton said he hopes the FDA’s action is part of a "broader effort to encourage people to consider how best to use these medications." When asked whether prescribers and their patients weren’t already addressing the risks and benefits involved in the use of these opioids, the current labeling for which indicates their use in patients experiencing "moderate to severe pain," rather than "round-the-clock" pain, Dr. Throckmorton said the labeling changes "will help reinforce the importance of the conversation in a busy practice."

The agency’s announcement comes amid growing data about the inherent risks of opioid use reported in the medical literature and the filing with the FDA of two citizen petitions to change how opioids are prescribed, including one by the Physicians for Responsible Opioid Prescribing. Also part of the focus on opioid use is the 19 to 10 vote by the FDA’s Drug Safety and Risk Management Advisory Committee in January to reschedule hydrocodone drug combinations from schedule III under the Controlled Substances Act (CSA) to schedule II. The vote was prompted by the U.S. Drug Enforcement Administration’s call for the FDA to react to evidence that the medications are overprescribed, diverted, and abused. Statistics cited by FDA officials in the briefing included nearly 16,000 opioid-related deaths in the United States in 2009, reflecting a 300% increase in the last 20 years.

Speaking about the importance of the dosage and duration of the medications, Dr. Throckmorton said the agency did not have enough information at this time to make changes to how these drugs are prescribed, but that the postmarket studies such as clinical trials, and other studies of at least 12 weeks’ duration, would play a role in providing this data. "We expect some of those studies will provide information for us to use in 2 years. So, by end of 2015, we will have more," Dr. Throckmorton said.

Also announced in the briefing was the addition of a boxed warning on extended-release/long-acting opioid analgesics to warn expectant mothers of neonatal opioid withdrawal syndrome (NOWS), which might be life-threatening and require management according to protocols developed by neonatology experts. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.