Sufentanil Sublingual Tablet (Dsuvia) Approved by FDA

The US Food and Drug Administration (FDA) has approved sufentanil sublingual tablet (Dsuvia) as a pain management therapy, sparking major concern among the lay public and professional health care sector alike. The drug is delivered through a disposable, pre-filled, single-dose applicator.

The approval is based on data from a multicenter trial in which patients were randomized 2:1 to receive either 30 mcg of the sufentanil sublingual tablet as needed, or placebo, with treatment limited up to 48 hours following the procedure. Patients treated with sufentanil reported meaningful pain relief in a median time of 54 minutes, compared with patients treated with placebo who reported meaningful pain relief in a median time of 84 minutes.

News outlets have decried the approval and emphasized sufentanil’s effects as “500 times more powerful than morphine;” however, Pamela Palmer, MD, PhD, chief medical officer of AcelRx Pharmaceuticals, which developed the drug, explained these overstatements are misguided.

“There are 2 key things to keep in mind,” Palmer said in an interview with MD Magazine®. “[Sufentanil sublingual tablet] is not for outpatient use. It is only going to be used in medically-supervised settings, which [will not] contribute to the outpatient abuse issue. In addition, potency, once it is dose-adjusted, is no longer a safety concern.”

Media coverage of the drug’s alleged “dangerous” potency is incorrect, according to Palmer. “If you conduct studies, dose-adjust for the potency, conduct dose-finding studies, and show that the dose is safe in young and old alike, then the issue of potency has been removed,” she said. “It’s very critical to get that across because it seems to be lost in the discussion.”

In terms of adverse events, the study investigators noted that more patients administered sufentanil suffered instances of nausea (n= 35 [32.7%]) and vomiting (8 [7.5%]), than patients on placebo (16, 1 [29.6%, 1.9%], respectively). Other adverse events in patients administered the therapy included headache (22 [20.6%]), dizziness (6 [5.6%]), and hypotension (6 [5.6%]).

Supplemental data recently presented at the American Society of Anesthesiologists (ASA) conference in San Francisco, CA, revealed that sufentanil was safe and efficacious compared with placebo in 2 open-label, single-arm trials of post-operative patients who received the therapy following bunionectomy or abdominal surgery.

Statistically significant improvements in pain intensity over 12 hours for patients on sufentanil versus those on placebo were reported. Nausea was the most commonly reported adverse event across patient populations.

Opponents of sufentanil’s approval have raised concerns that even though the drug can only be administered in medically-supervised settings, that may not stop nefarious actors from stealing the medication for personal use (or to sell for profit).

To this point, Palmer, who worked on the frontlines of the opioid crisis at the University of California San Francisco Pain Management Center for 13 years and focused on outpatient chronic pain management, highlighted data from the Substance Abuse and Mental Health Administration which indicated that of abused opioids, only .7% are stolen from medically-supervised settings.

Furthermore, by having a Risk Evaluation and Mitigation Strategy that sequesters the drug only to medically-supervised settings, she explained that over 99% of the risks of abuse and diversions are already taken care of.

FDA Commissioner Scott Gottlieb, MD, also addressed some of the previously communicated concerns over the sufentanil sublingual tablet, reiterating that the medication is limited to strict use in certified medically-supervised health care settings for administration by a health care professional while also highlighting patients for which the medication will be most appropriate.

“Some unique features [of sufentanil sublingual tablet is] that the drug is delivered in a stable form that makes it ideally suited for certain special circumstances where patients may not be able to swallow oral medication, and where access to intravenous pain relief is not possible,” Gottlieb said. “This includes potential uses on the battlefield [for military personnel]… a specific and important, but limited, unmet medical need.”

Despite Gottlieb’s statement and reassurances on the safety of the drug, Raeford Brown, MD, FAAP, chair of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee, shared serious concerns about the new approval.

“I am very disappointed with the decision of the agency to approve the sufentanil sublingual tablet,” Brown said in a recent statement. “This action is inconsistent with the charter of the agency. [T]he lack of efficacy data and the sponsor’s inadequate response to safety concerns have not been addressed since the FDA’s complete response letter was sent in 2017. Clearly, the issue of the safety of the public is not important to the commissioner, despite his attempts to obfuscate and misdirect. I will continue to hold the agency accountable for their response to the worst public health problem since the 1918 influenza epidemic.”

Perhaps preemptively expecting the outcry, Gottlieb addressed these concerns in his statement, adding, “Looking beyond this particular drug approval, I believe that we should consider whether we should be doing more to evaluate each candidate opioid, not just as an independent review decision, but rather also to consider each novel opioid drug in the context of the overall therapeutic armamentarium that’s available to patients and providers.”

“As part of the effort to consider and apply a more holistic approach,” he continued. “I will also be taking these questions, and a consideration of such a framework, to my Opioid Policy Steering Committee to evaluate what additional steps we may want to take within our own authority to consider these goals and the development of such a framework.”