FDA Supports Greater Access to Naloxone to Help Reduce Opioid Overdose Deaths

By: Karen Mahoney, M.D.

Overdose deaths involving prescription opioids such as oxycodone, hydrocodone and morphine and illicit opioids such as heroin and illegally produced fentanyl have more than tripled since 1999 – with about 28,000 people dying in 2014 alone.

Many of these tragedies could have been avoided if the people experiencing the overdose had immediately received the prescription drug naloxone, a life-saving medication that can stop or reverse the effects of an opioid overdose.

Naloxone is still a prescription in all 50 states and the District of Columbia, though many have or are taking steps to make naloxone more accessible. Consistent with our opioid action plan announced earlier this year, the FDA is exploring options to make naloxone more available to treat opioid overdose. One option to do this is identifying ways to assist manufacturers in submitting an application to the FDA for an over-the-counter (OTC) version of a naloxone product.

That’s why the FDA is working on innovative ways to help facilitate the process of helping manufacturers pursue approval of an OTC naloxone product, including helping to develop the package label that would be required for such a product. This is an important step to help increase access to and the use of this life-saving drug.

Although the two currently available prescription naloxone products intended for use in the community — an auto-injector product for self-injection, and a nasal spray formulation – have instructions for use, they do not have the consumer-friendly Drug Facts Label (DFL), which is required for OTC drug products. Before submitting a new drug application or supplement for an OTC drug product, companies develop this DFL and conduct the required studies to show that consumers can follow the DFL to understand how to use the product without the help of a healthcare professional.

To help facilitate the development of OTC naloxone, the FDA has created a model DFL and an accompanying simple pictogram that could be placed next to the DFL to visually correspond to the label directions. This model DFL and pictogram are intended to provide consumers with the information they would need to understand how to safely use naloxone, including when it is appropriate to purchase naloxone and how to use it in an emergency opioid overdose situation. Since it is a model label, information that is highly specific to a particular product would not be included.

The FDA has also arranged for label comprehension testing of the model DFL. This testing is now being conducted and we expect that the results will yield important information about consumer understanding of the model naloxone DFL. Using this information, naloxone manufacturers may then be able to focus their final label comprehension testing on how well consumers understand product-specific information, such as instructions for the device that delivers naloxone that has not been already tested on the model DFL.

Creating a model DFL and arranging for label comprehension testing are among the ways that the FDA is working to fulfill our commitment to enhanced naloxone access, where possible, in our opioids action plan. We will continue to work with interested manufacturers and developers to further explore the best uses of naloxone for the emergency treatment of known or suspected opioid overdoses until emergency medical help arrives.

FDA’s opioid action plan is part of the comprehensive Opioid Initiative launched by the U.S. Department of Health and Human Services (HHS) in March 2015. The Initiative focuses on high-impact strategies to 1) improve opioid prescribing, 2) expand access to medication-assisted treatment for opioid use disorders, and 3) increase the use of naloxone to reverse opioid overdoses.

Karen Mahoney, M.D., is FDA’s Deputy Director, Division of Nonprescription Drug Products, at the Center for Drug Evaluation and Research

Crafting better drug labeling to ensure safer use of opioids

By: Margaret A. Hamburg, M.D.

One of the FDA’s primary public health missions is ensuring that healthcare providers and their patients have all the information they need to help decide whether a medication is safe and appropriate to use.

Margaret Hamburg, M.D.Communicating the full risks and benefits of a drug becomes all the more important for those medications that are potentially deadly if used incorrectly. Extended-release long-acting(ER/LA) opioids fall into that category, and can sometimes cause serious harm, like addiction, even when used properly.

These medications, which include drugs such as morphine, oxycodone, and fentanyl, can improve the quality of life for many people who must live every day with pain. But ER/LA opioids often also contain a large amount of the active ingredient, sometimes in sufficient quantity to be lethal, and they are a prime target of drug abusers.

As part of FDA’s efforts to address the serious risks of ER/LA opioids, we looked more closely at the product labeling, known by many as the package insert, to determine whether this essential tool for conveying information about a drug should be revised to encourage safer use.

We closely reviewed medical literature and evaluated public input. We then came to the conclusion that if we improved what the labeling says about proper patient selection and the risks from these drugs, we might be able to reduce the frequency of bad outcomes.

And so today I’m pleased to announce new, proposed labeling changes for ER/LA opioid pain relievers, as well as new postmarket requirements that will include additional studies and clinical trials to better assess certain significant questions about the risks and safety practices of these drugs. The goal is to achieve safer and more appropriate use of these potent pain relievers.

These labeling changes better describe the risks associated with the ER/LA opioid medications and clarify the population for whom the benefits of these products outweigh their risks.

Rather than stating that these medications are indicated “for the relief of moderate to severe pain in patients requiring continuous, around-the clock opioid treatment for an extended period of time,” once final, the updated label will clarify that these products are indicated for “management of pain severe enough to require daily, around the clock, long-term opioid treatment and for which alternative treatment options are inadequate.”

And in the section of the label regarding limitations of use, we have added language plainly stating just how risky these drugs are — even at recommended doses.

In addition, we are requiring changes to the boxed warning for these products to give greater emphasis and prominence to the risk of Neonatal Opioid Withdrawal Syndrome that may occur in newborns due to prolonged opioid exposure during gestation.

We know that the way a patient characterizes pain is always going to be subjective: “moderate” pain for one patient may be “severe” pain to another. And we recognize that there are some women who have an appropriate need for opioids during their pregnancy.

The goal of all of these labeling changes is to help physicians work with their patients to determine whether these potent pain relievers are the most appropriate treatment for their specific situation and if so, to help them in managing their use.

While our intent is to encourage safer and more appropriate use of these products, simply changing the labeling won’t make an impact if these changes are not understood and integrated into practice by healthcare providers. So I am urging prescribers to spend some time going over this new labeling, when final, reflecting on what the language means to their practice, and communicating what they’ve learned to their patients.

The fact is, improving the safe and appropriate use of ER/LA opioids takes the help and commitment of all of us, including our partners in the healthcare community. We are committed to working together to help ensure that healthcare providers can prescribe ER/LA opioids properly and better monitor and educate their patients.

Margaret A. Hamburg, M.D., is the Commissioner of the Food and Drug Administration