FDA Approves, Explains Need for New Acute Pain Sufentanil Formulation

Author: Donald M. Pizzi

Anesthesiology News

The FDA approved a sufentanil sublingual tablet (Dsuvia, AcelRx) for the management of acute pain in adults that is severe enough to require an opioid analgesic in certified medically supervised health care settings, such as hospitals, surgical centers and emergency departments.

The drug comes with a complicated approval history. An FDA advisory committee recommended that the agency approve the product. However, the panel’s chairman, Raeford E. Brown Jr., MD, a professor of anesthesiology and pediatrics at the University of Kentucky, in Lexington, wrote a letter to the FDA following the vote stating his concerns, calling it a “an easily divertible drug” that could lead to abuse, overdose and death.

Dsuvia, the development of which was cofunded by the Department of Defense, is a 30-mcg sufentanil tablet in a single-dose, prefilled applicator. The single-strength tablet and single-unit packaging are designed to mitigate the possibility of dosing errors, misuse and diversion, according to AcelRx. “The sublingual administration makes Dsuvia an option for patients with nothing by mouth [NPO] status and patients with difficult IV access [obese, elderly, burn or needle-phobic patients],” the company wrote in a press statement.

The drug’s commercial launch is expected in the first quarter of 2019.

The efficacy and safety of the sufentanil tablet were evaluated in a randomized, double-blind, placebo-controlled trial that enrolled 161 patients (age, 18-69 years) with acute postoperative pain (pain intensity ≥4 on a 0-10 numeric rating scale) after abdominal surgery (studied up to 48 hours). Patients were dosed with 30 mcg of sufentanil or placebo as needed, with a minimum of 60 minutes between doses. Intravenous morphine sulfate 1 mg was available as a rescue medication.

Patients using sufentanil had a significantly greater improvement over the first 12 hours of the study than those using placebo. Approximately 22% of patients in the sufentanil group and 65% of those in the placebo group took rescue medication within the first 12 hours of the treatment phase.

In controlled and uncontrolled studies, the safety of sufentanil was evaluated in a total of 646 patients with moderate to severe postoperative pain or pain due to trauma that required opioid analgesia.

The most frequently reported adverse reactions seen in 2% or more of patients in the randomized, placebo-controlled trial were nausea, headache, vomiting, dizziness and hypotension. “The Dsuvia clinical program builds upon the established safety and efficacy of the reference product, sufentanil citrate injection, which has been in commercial use for over three decades,” wrote AcelRx in a press statement.

Sufentanil will not be available in retail pharmacies or for outpatient use. The drug will only be distributed to health care settings certified in the Dsuvia Risk Evaluation and Mitigation Strategy (REMS) program “following attestation by an authorized representative that the health care setting will comply with appropriate dispensing and use restrictions of Dsuvia,” AcelRx wrote. As part of the REMS program, AcelRx will monitor distribution and audit wholesalers’ data, evaluate proper usage within the health care settings, and monitor for any diversion and abuse. Additionally, AcelRx will decertify health care settings that are noncompliant with the REMS program. Like all opioids, sufentanil will also carry a boxed warning about the serious risks of misuse and abuse, which can lead to addiction, overdose and death.

After the approval, FDA Commissioner Scott Gottlieb, MD, acknowledged the difficulties the agency faces in approving new drugs in the class during the current opioid epidemic.

“I believe that the unique aspects of Dsuvia, including those that make this drug a high priority for the Pentagon, differentiate this new formulation of sufentanil from other sufentanil products in a way that is consistent with population-based considerations for how it fits into the overall drug armamentarium,” Dr. Gottlieb said. “The FDA has made it a high priority to make sure our soldiers have access to treatments that meet the unique needs of the battlefield, including when intravenous administration is not possible for the treatment of acute pain related to battlefield wounds,” he said. “The military application for this new medicine was carefully considered in this case.

“We won’t sidestep what I believe is the real underlying source of discontent among the critics of this approval,” he wrote. “As a public health agency, we have an obligation to address this question openly and directly. As a physician and regulator, I won’t bypass legitimate questions and concerns related to our role in addressing the opioid crisis.”