By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a highly potent opioid analgesic for acute severe pain reserved for use in certain medically supervised healthcare settings. This sublingual formulation of sufentanil is 10 times more potent than fentanyl and 100 times more potent than morphine. The tablets were developed in collaboration with the Department of Defense and will be marketed as Dsuvia through a restricted Risk Evaluation and Mitigation Strategy program.
Sufentanil sublingual tablets (sufentanil-SLT) are for adults with acute pain that is severe enough to require an opioid analgesic for which different treatments have proven insufficient.1 Providers are expected to administer the drug in a certified, medically supervised healthcare setting.
The recommended dose is 30 mcg given sublingually via a single-dose applicator, as needed, with a minimum of one hour between doses. The dose is not to exceed 12 tablets in 24 hours and for a duration of no more than for 72 hours.1 Sufentanil-SLT is available as a 30 mcg tablet in a disposable, tamper-evident, single-dose applicator.
Sufentanil-SLT provides an alternative in a setting in which the patient cannot swallow oral medication and access to IV administration of an analgesic is not possible or may be delayed (e.g., battlefield).
Because of its potency, sufentanil-SLT likely will increase the risk of serious, life-threatening, or fatal respiratory depression as well as the risk for diversion and abuse. Since the drug is metabolized by CYP3A4, concomitant use with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers can result in fatal overdose.1
Sufentanil-SLT has a smaller safety margin with concurrent use with benzodiazepines or other central nervous system depressants and accidental exposure. It is contraindicated in patients with acute or severe bronchial asthma and known or suspected gastrointestinal obstruction. Patients with COPD, patients who are elderly, cachectic, or debilitated, and patients with increased intracranial pressure require close monitoring.
Sufentanil-SLT onsets rapidly, with a duration of analgesia of about three hours.2 The efficacy and safety were evaluated in one randomized, placebo-controlled trial that included 161 subjects with moderate-to-severe acute postoperative pain (≥ 4 on an 11-point numeric rating scale) after abdominal surgery.1,2 These procedures included abdominoplasty, open inguinal hernioplasty, or laparoscopic abdominal surgery. Subjects received sufentanil-SLT 30 mcg (n = 107) or placebo (n = 54) on an as-needed basis, with a minimum of 60 minutes between doses. IV morphine was available as rescue medication. The primary efficacy endpoint was the time-weighted summed pain intensity difference over 12 hours (SPID12).
Sufentanil-SLT showed statistically significant SPID12 over placebo. The onset of analgesia occurred within 15-30 minutes, with median time to meaningful pain relief of 54 minutes for sufentanil-SLT vs. 84 minutes for placebo. Approximately 22% of subjects assigned to sufentanil-SLT took rescue analgesic vs. 65% with placebo. The safety of sufentanil-SLT was assessed in 646 subjects. Half the subjects in the safety assessment were on the 15 mcg formulation approved in the Europe Union.2 There were no data on subjects ≥ 75 years of age on the higher dose. The most frequently reported (> 10%) adverse reactions were nausea (29%) and headache (12%). Less frequent adverse reactions included vomiting (5.6%), dizziness (5.6%), and hypotension (4.7%).
Sufentanil-SLT is a highly potent opioid analgesic that is the sublingual form of sufentanil, a drug that has been available since 1984. Currently, there are no data comparing sufentanil-SLT to other analgesics; thus, relative potency cannot be determined.
Critics have questioned the need for such a potent opioid, given the current addiction crisis. The drug received a favorable vote in a session of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC). However, AADPAC Chairperson Raeford E. Brown, Jr., MD, who opposes the drug, was unable to attend that meeting.3 Brown and others cited absence of full participation of the FDA’s Drug Safety and Risk Management Advisory Committee during the review and substantial risk of respiratory depression, diversion, abuse, and death (including among anesthesiologists).
However, FDA Commissioner Scott Gottlieb, MD, defended the approval, citing it fills a targeted medical need and there are adequate limitations on its use.4
- Dsuvia Prescribing Information. AcelRx Pharmaceuticals, Inc., November 2018. Available at: . Accessed Nov. 21, 2018.
- FDA Briefing Document. Anesthetic and Analgesic Drug Products Advisory Committee, Oct. 12, 2018. Available at: . Accessed Nov. 21, 2018.
- Public Citizen. Letter to the FDA, Oct. 18, 2018. Available at: . Accessed Nov. 21, 2018.
- U.S. Food & Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on agency’s approval of Dsuvia and the FDA’s future consideration of new opioids, Nov. 2, 2018. Available at: . Accessed Nov. 21, 2018.