FDA approval of powerful opioid tinged with irony

The timing of the Food and Drug Administration’s Nov. 2 approval of the medication Dsuvia, a sublingual formulation of the synthetic opioid sufentanil, is interesting – to say the least. Dsuvia is a powerful pain medication, said to be 10 times more potent than fentanyl and 1,000 times more potent than morphine. The medication, developed by AcelRx Pharmaceuticals for use in medically supervised settings, has an indication for moderate to severe pain, and is packaged in single-dose applicators.

Dr. Dinah Miller

The chairperson of the FDA’s Anesthetic and Analgesics Drug Product Advisory Committee, Raeford E. Brown Jr., MD, a professor of pediatric anesthesia at the University of Kentucky, Lexington, could not be present Oct. 12 at the committee vote recommending approval. With the consumer advocacy group Public Citizen, Dr. Brown wrote a letter to FDA leaders detailing concerns about the new formulation of sufentanil.

“It is my observation,” Dr. Brown wrote, “that once the FDA approves an opioid compound, there are no safeguards as to the population that will be exposed, the postmarketing analysis of prescribing behavior, or the ongoing analysis of the risks of the drug to the general population relative to its benefit to the public health. Briefly stated, for all of the opioids that have been marketed in the last 10 years, there has not been sufficient demonstration of safety, nor has there been postmarketing assessment of who is taking the drug, how often prescribing is inappropriate, and whether there was ever a reason to risk the health of the general population by having one more opioid on the market.”

Dr. Brown went on to detail his concerns about sufentanil. In the intravenous formulation, the medication has been in use for more than two decades.

“It is so potent that abusers of this intravenous formulation often die when they inject the first dose; I have witnessed this in resuscitating physicians, medical students, technicians, and other health care providers, some successfully, as a part of my duties as a clinician in a major academic medical center. Because it is so potent, the dosing volume, whether in the IV formulation or the sublingual form, can be quite small. It is thus an extremely divertible drug, and I predict that we will encounter diversion, abuse, and death within the early months of its availability on the market.”

The letter finishes by criticizing the fact that the full Drug Safety and Risk Management Advisory Committee was not invited to the Oct. 12 meeting, and finally, about the ease of diversion among health care professionals – and anesthesiologists in particular.

Meanwhile, Scott Gottlieb, MD, commissioner of the FDA, posted a lengthy explanation on the organization’s website on Nov. 2, after the vote. In his statement on the agency’s approval of Dsuvia and the FDA’s future consideration of new opioids, Dr. Gottlieb explains: “To address concerns about the potential risks associated with Dsuvia, this product will have strong limitations on its use. It can’t be dispensed to patients for home use and should not be used for more than 72 hours. And it should only be administered by a health care provider using a single-dose applicator. That means it won’t be available at retail pharmacies for patients to take home. These measures to restrict the use of this product only within a supervised health care setting, and not for home use, are important steps to help prevent misuse and abuse of Dsuvia, as well reduce the potential for diversion. Because of the risks of addiction, abuse, and misuse with opioids, Dsuvia also is to be reserved for use in patients for whom alternative pain treatment options have not been tolerated, or are not expected to be tolerated, where existing treatment options have not provided adequate analgesia, or where these alternatives are not expected to provide adequate analgesia.”

In addition to the statement posted on the FDA’s website, Dr. Gottlieb made the approval of Dsuvia the topic of his weekly #SundayTweetorial on Nov. 4. In this venue, Dr. Gottlieb posts tweets on a single topic. On both Twitter and the FDA website, he noted that a major factor in the approval of Dsuvia was advantages it might convey for pain control to soldiers on the battlefield, where oral medications might take time to work and intravenous access might not be possible.

One tweet read: “Whether there’s a need for another powerful opioid in the throes of a massive crisis of addiction is a critical question. As a public health agency, we have an obligation to address this question for patients with pain, for the addiction crisis, for innovators, for all Americans.”

Another tweet stated, “While Dsuvia brings another highly potent opioid to market it fulfills a limited, unmet medical need in treating our nation’s soldiers on the battlefield. That’s why the Pentagon worked closely with the sponsor on developing Dsuvia. FDA committed to prioritize needs of our troops.”

Given our national overdose crisis, and issues of addiction with our soldiers and veterans, one has to wonder if the improvements afforded in pain control by Dsuvia will be worth the trade-off in possible deaths from misdirected use of a very potent agent. And while the new opioid may have been geared toward unmet military needs, Dsuvia will be available for use in civilian medical facilities as well.

There is some irony to the idea that a pharmaceutical company would continue to develop opioids when there is so much need for nonaddictive agents for pain control and so much pressure on physicians to limit access of opiates to pain patients. We are left to stand by and watch as yet another potent opioid preparation is introduced.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore.