Sublingual form approved for short-term use.
The FDA approved sublingual sufentanil (Dsuvia, AcelRx Pharmaceuticals) in November for management of severe acute pain refractory to alternative treatments in adults being treated in a medically supervised healthcare setting. Sufentanil is a relatively selective full agonist of the mu-opioid receptor, which provides analgesia and sedation.1
The efficacy of sublingual sufentanil was assessed in three Phase 3 clinical trials.2-4 SAP301 was a multicenter double-blind placebo-controlled trial with 161 participants that compared 30 mcg of sublingual sufentanil to placebo for postoperative pain following abdominal surgery. The primary outcome is the summed pain intensity difference over 12 hours (SPID12), which uses a score from 0 (no pain) to 10 (worst possible pain) to calculate the difference in pain intensity over the 12 hours. Sublingual sufentanil showed a statistically significant greater difference in SPID12 compared to placebo.
SAP302 was an open-label study with 76 participants assessing safety and efficacy of 30 mcg of sublingual sufentanil for moderate-to-severe acute pain in emergency room patients with obvious trauma or injury. The primary outcome was the summed pain intensity difference over 1 hour (SPID1). Pain was measured at baseline and every 15 minutes over the hour and then hourly for 5 hours. The study demonstrated a decrease in the pain intensity of participants during the study period.
SAP303 was a multicenter open-label trial with 140 participants assessing safety and efficacy of 30 mcg sublingual sufentanil for postoperative pain. Similar to SAP302, the primary outcome is the SPID12. Results demonstrate a decrease in pain intensity of participants during the 12-hour study period.
The safety of sublingual sufentanil was assessed in a total of 646 patients in both controlled and uncontrolled studies, including SAP301, SAP302, and SAP303.1 In the combination of all three SAP studies, two patients in the sublingual sufentanil groups reported a severe adverse event. One patient in the SAP302 study experienced angina pectoris, and one in the SAP303 study experienced an acute stroke.3,4 Sublingual sufentanil was well-tolerated by patients, Adverse effects occurring in more than 10% of patients included nausea and headache.2-4
Serotonin syndrome has been reported in patients taking sufentanil and serotonergic drugs.
Sublingual sufentanil should not be used for more than 72 hours as it has not been studied beyond this time frame. Its use in pediatrics is not recommended because safety and efficacy in this population have not been established. Geriatric patients should be monitored closely due to risk of central nervous system and respiratory depression. Use caution in pregnant patients as prolonged use of opioids can lead to neonatal opioid withdrawal syndrome.
Sublingual sufentanil is a single-use tablet that must be administered by a healthcare professional in a certified medically supervised healthcare setting. The tablet should be delivered to the space under the tongue using a prefilled applicator to limit accidental exposure to the healthcare professional and to ensure proper placement. The recommended dose of sublingual sufentanil is 30 mcg as needed. The maximum cumulative daily dose is 12 tablets (360 mcg) with a minimum of 1 hour between doses.1
1. Sufentanil sublingual package insert. Redwood City, CA: AcelRx Pharmaceuticals, Inc.; 2018
2. ClinicalTrials.gov [Internet]. 2017 Feb. 13. NCT02356588; A trial evaluating the efficacy and safety of the sublingual sufentanil tablet 30 mcg for post-operative pain after abdominal surgery: Available at: https://clinicaltrials.gov/ct2/show/NCT02356588. Accessed on Jan. 3, 2019.
3. ClinicalTrials.gov [Internet]. 2017 March 15. NCT02662556; A multicenter, open-label trial to evaluate the safety and efficacy of the sufentanil sublingual tablet 30 mcg in patients with post-operative pain: Available at: https://clinicaltrials.gov/ct2/show/results/NCT02662556. Accessed on Jan. 3, 2019.
4. ClinicalTrials.gov [Internet]. 2017 Oct. 19. NCT02447848. Open-label safety and efficacy of the sufentanil sublingual tablet 30 mcg for acute pain: Available at: https://clinicaltrials.gov/ct2/show/NCT02447848. Accessed on Jan. 3, 2019.