Label Changes and New Postmarketing Requirements for Opioids

Across the United States, reports have revealed the increasing epidemic of people abusing, misusing, and dying from opioids and other prescription pain medications. The trend has caused government officials, pharmaceutical companies, and advocates to debate the best use of these drugs and led to modifications in how the products are manufactured and marketed.

In September, the FDA announced labeling changes and new postmarketing requirements for extended-release and long-acting opioid pain relievers. The decision affects products containing fentanyl, oxycodone, oxymorphone, morphine and methadone.

The labels will now alert patients and healthcare professionals that the drugs should be used only when other options are inadequate to manage severe pain needing continuous, long-term treatment. They used to indicate the drugs could also be used for moderate pain. Alternative pain treatments include non-opioid analgesics and short-acting, immediate-release opioids. Extended-release and long-acting opioids have a longer effect and usually contain a higher dose of drug compared with immediate release products or those combining opioids and non-opioids. The FDA will also require companies to conduct long-term studies to evaluate the risks associated with extended-release and long-acting opioids. Before approving opioids, the FDA mandates that manufacturers have 12-week trials, so there is not much information about whether the drugs are safe and effective beyond that time period.

“I think it’s a very good thing,” Robert Twillman, PhD, director of policy and advocacy at the American Academy of Pain Management, said in an interview with First Report Managed Care. “We have admitted we don’t have those data. We do need to know [if the drugs work]. What we know clinically is that there are some people who do very well for years on these medications. We know there are some people who develop all sorts of problems with them, too. How many there are, what the risk factors are, all this stuff, we just don’t know, and we need to.”

However, with the new requirements, Dr. Twillman is concerned that more health insurers may implement step therapy protocols in which all pain patients will begin treatment with non-steroidal anti-inflammatory drugs and then continue to non-opioids or short-acting opioids before being allowed to take extended-release and long-acting opioids. He agrees that most patients with pain should receive opioids, although some need to take the FDA-approved medications immediately after diagnosis. In some step therapy programs, patients wait two years until they can receive extended-release and long-acting opioids, according to Dr. Twillman.

The Institute of Medicine released a report in 2011 that mentioned more than 100 million people in the United States suffer from chronic pain. Between 1999 and 2008, sales of prescription pain medications and opioids more than tripled, according to a Centers for Disease Control and Prevention report from July. In 2008, 14,800 people died from overdosing on pain medications, more than died from abusing cocaine and heroin combined. A year later, more than 475,000 visits to the emergency department were related to people misusing or abusing pain drugs.

As the problems continued, a group of doctors and healthcare professionals created the Physicians for Responsible Opioid Prescribing (PROP) in late 2010. The group was concerned that opioids were overprescribed and that many people had a poorer quality of life and could become addicted when told to take long-term opioids.

Andrew Kolodny, MD, a psychiatrist from New York and the PROP president, said the benefits outweigh the risks when opioids are used for short-term acute pain and for suffering at the end of life. When opioids are used long-term for conditions such as fibromyalgia, low back pain, and headaches, the risks likely outweigh the benefits, according to Dr. Kolodny.

“We’re pleased the FDA removed moderate from the labels for extended relief opioids, but we thought the FDA should have gone much further,” Dr. Kolodny said in an interview with First Report Managed Care. “I think the language for the label looks like it could have been written by a drug company lawyer. I think that the FDA was not interested in making changes to labels that the manufacturers and the organizations they fund and the pain industry [would oppose]. They weren’t going to upset those stakeholders.”

The labeling and postmarketing changes are the most recent steps the government has taken to address the issue. Last July, the FDA approved a Risk Evaluation and Mitigation Strategy (REMS) program for extended-release and long-acting opioid pain relievers. Companies that manufacture the drugs now must make educational programs available to prescribers, although the prescribers are not required to sign up for the programs. The REMS also includes a medication guide for patients on how to safely use and dispose of opioid analgesics.

The FDA has continued to consider placing more restrictions on hydrocodone, as well. The Drug Enforcement and Administration has urged the FDA for several years to re-classify hydrocodone-containing drugs because they have been linked to abuse and misuse. In January, an FDA advisory committee voted 19 to 10 in favor of moving products containing hydrocodone from Schedule III to Schedule II, a category that includes fentanyl, oxycodone, oxymorphone, morphine and methadone. As of early October, though, the FDA had not made a final decision. If hydrocodone is moved to Schedule II, patients will have a more difficult time re-filling prescriptions and pharmacies and wholesalers will have to implement more security protocols.

Another safety measure occurred in April, when the FDA banned generic companies from manufacturing oxycodone drugs that aren’t tamper-resistant. Instead of taking oxycodone orally, millions of people have crushed the pills and chosen to snort or inject the medications, which has contributed to abuse and deaths. Dr. Twillman said he believes that from now on, the FDA will only approve opioids that are tamper-resistant.