Author: Bob Kronemyer
In medically supervised settings, the sufentanil sublingual tablet (ssT; Dsuvia, AcelRx Pharmaceuticals) has been found to be well tolerated for the short-term treatment of moderate to severe acute pain, with at most moderate levels of adverse events. This study (Pain Med 2019 Jan 7. was a pooled phase 3 safety analysis of 804 patients administered the ssT.
“This pooled safety analysis was conducted as part of the New Drug Application for Dsuvia,” said James Miner, MD, FACEP, a professor of emergency medicine at the University of Minnesota Medical School, in Minneapolis, and a clinical investigator and consultant for the marketer, AcelRx Pharmaceuticals. “While the results of the individual studies had been previously published, the pooled safety data from over 800 patients had not. It was important to publish this data so that physicians can gain insight into the appropriate use of Dsuvia and the safety profile of the drug.”
Dr. Miner said he was impressed by the low adverse event rates for vomiting and decreased oxygen saturation (3.6%) related to the ssT, in both his own practice and the pooled analysis. “These are the two adverse events that we are most concerned about as physicians when treating our patients with opioids,” said Dr. Miner, the principal investigator of the safety analysis, as well as lead investigator and author of the SAP302 (open-label safety and efficacy) emergency department study of the ssT (Am J Emerg Med 2018;36:954-961).
As the chief of emergency medicine at Hennepin County Medical Center in Minneapolis, Dr. Miner is concerned about cognitive impairment in the emergency setting. “Based on the Six-Item Screener cognitive impairment measure, we found that over 97% of patients had either the same or an improved score one hour after dosing compared to their predosing score,” he said (Table).
|Table. The Six-Item Cognitive Screen|
|First, ask the patient to repeat and remember these words: Apple–Table–Penny. The interviewer may repeat the words three times if necessary for repetition to count.||Yes||No|
|1. What year is this?||0||1|
|2. What month is this?||0||1|
|3. What is the day of the week?||0||1|
|What were the three objects I asked you to remember?|
|Total of ≥4 means impairment is less likely.|
“Having seen a significant degree of cognitive effects of IV morphine and IV hydromorphone in patients over the years, I welcome a noninvasive analgesic with minimal cognitive impact that will allow me to rapidly treat my patients in moderate or severe pain.”
In addition, it is important to use opioids as part of a multimodal approach to moderate to severe pain, according to Dr. Miner. “Using lower doses of multiple agents reduces the side effects of any single agent.”
Along with the pooled safety data, the article notes the dissolution time of the ssT and the relative dose equivalents to IV morphine, to educate physicians on what to expect following dosing of the tablet.
“The ssT formulation has an average dissolution time of six minutes,” Dr. Miner said. “Therefore, patients are asked to not eat or drink and to minimize talking for 10 minutes following dosing to avoid swallowing the drug, as the gastrointestinal bioavailability is less than 10%.”
A calculation of the dose equivalents to IV morphine was conducted on an earlier comparative study of an ssT and IV morphine, which determined that a 30-mcg ssT is roughly dose-equivalent to 5 mg of IV morphine.
As for the issue that patients will abuse the ssT, Dr. Miner said the ssT is a Schedule II drug and will be stored and disposed of in the same way as all other Schedule II drugs in the hospital. “In contrast to IV opioids in the hospital, Dsuvia has a Risk Evaluation and Mitigation Strategy (REMS) program, which AcelRx and the FDA jointly defined,” he said.
The REMS program is notable in that the ssT’s distribution will be limited to REMS-certified medically supervised settings. “Medically supervised settings must attest that Dsuvia will not be dispensed to patients for use outside of the certified setting,” Dr. Miner said. “Importantly, the restricted distribution of Dsuvia mitigates the vast majority of the risk of diversion.”
Dr. Miner pointed out that the most recent annual report from the Substance Abuse and Mental Health Services Administration, analyzing 2017 data, shows that only 0.5% of the abused opioids is stolen from medically supervised settings. “Hence, limiting Dsuvia use to only these settings will help avoid the abuse that plagues the outpatient opioid products.”