First-in-Class Drug Approval for Acute Pain Highlights Need for Nonopioid Therapies
Pharmacists are well positioned to screen for diversion, monitor for opioid use disorder, and educate patients on opioid-related risks.
In January 2025, the FDA approved the first and only nonopioid analgesic, suzetrigine (Journavx), to treat moderate to severe acute pain in adults. Suzetrigine reduces pain by targeting pain-signaling pathways before pain signals reach the brain, according to the FDA.1
“Any pain management treatment option that is not an opioid is typically well received these days, as not only [does] the sensationalized anti-opioid hysteria continue its reign, [but] also the realistic desire of clinicians to provide actual safe and effective patient care for those in pain remains,” Mark Garofoli, PharmD, MBA, BCGP, CPE, CTTS, director of experiential learning at West Virginia University School of Pharmacy and clinical pain and addiction pharmacist at West Virginia University Medicine, said. “Suzetrigine is FDA approved for moderate to severe—numerical pain scale range of 4 to 10—acute pain in adults, leaving patient care opportunities rather wide open.”
Pharmacists are well positioned to screen for diversion, monitor for opioid use disorder, and educate patients on opioid-related risks. | Image Credit: BillionPhotos.com - stock.adobe.com
This approval marks the first in a new class of pain management medications and is aimed at developing nonopioid analgesics for acute pain.1
It is unclear how the new approval will affect the opioid pandemic. However, in an interview, Madison Irwin, PharmD, BCPS, a clinical pharmacist specialist in palliative care at the University of Michigan Health and a clinical assistant professor at the University of Michigan College of Pharmacy, discussed how insurance coverage could influence the impact of the approval.
“Vertex [Pharmaceuticals Incorporated], which is [suzetrigine’s manufacturer], is reporting they’ve established a wholesale acquisition cost of $15.50 per 15-mg tablet, and so, per their recommended dosing and the label dosing, [that] would be around $30 a day,” Irwin said. “It’s also not astronomically high, so I don’t know if that will be as much of a limiting factor as with some other drugs, but it certainly will have an impact.”2
A HISTORY OF OPIOIDS IN THE UNITED STATES
Opioids have been separated into 3 categories: natural, semisynthetic, and synthetic. Natural opioids, also referred to as opiates, include morphine, and synthetic opioids include methadone and fentanyl, which are wholly made in a laboratory. Semisynthetic opioids include many of the prescription pain medications, including oxycodone and hydrocodone, which are synthesized from morphine and codeine.3
According to a report from the Congressional Research Service, the 1990s brought more intense marketing for nearly reformulated prescription opioid medications, such as oxycodone hydrochloride (OxyContin), which was paired with a pain advocacy campaign, leading to the rise in opioid use in the US. From 1999 to 2010, opioid prescription sales quadrupled, and misuse and overdose-related deaths also increased. Between 1999 and 2020, approximately 565,000 Americans died from opioid-involved overdoses, leading federal, state, and local governments to respond to the epidemic.3
Further, the COVID-19 pandemic may have exacerbated the impact of the opioid crisis, which showed significant increases in alcohol and substance misuse, according to the Federal Communications Commission. However, the CDC suggests that the increased use of telehealth for opioid use disorder (OUD)–related services was associated with a lowered likelihood of fatal drug overdoses for patients who had Medicare.4,5
“The necessary isolation efforts and the general psychology of dealing with such a worldwide scenario propelled many to more drug utilization. Drug overdose deaths increased during the pandemic yet are thankfully slowly starting to decrease to prepandemic levels these days, a trend that many hope continues,” Garofoli said.
The opioid epidemic has been separated into 3 waves. The first wave began with the increased opioid prescriptions in the 1990s, with the marked increase starting around 1999. The second wave began in 2010, with increases in opioid deaths involving heroin specifically. The third wave began in 2013, with substantial increases in overdose deaths that involved synthetic opioids, particularly fentanyl or fentanyl analogues. Fentanyl is often found as a powder or pressed into counterfeit pills and can be mixed into other drugs. The CDC reports that many opioid deaths involve other drugs, with nearly 43% of drug overdose deaths in 2022 involving both opioids and stimulants.6
Out health care system is so very complicated that one should take pause [at] the reality that it's rather hard to [obtain] a prescription pain medication these days. —Mark Garofoli, PharmD, MBA, BCGP, CPE, CTTS
“I think the important thing to remember with suzetrigine right now is that it has been studied in and is indicated for acute [pain], and so certainly it has the potential to reduce the use of opioids perioperatively, which is how it was studied,” Irwin said. “It remains to be seen what its place is going to be in the chronic pain space.”2
SUZETRIGINE'S POTENTIAL ROLE IN THE OPIOID CRISIS
The approval of suzetrigine was evaluated in 2 randomized, double-blinded trials for acute surgical pain—one for abdominoplasty and the other for bunionectomy. Investigators found that at the highest dose, the drug reduced acute pain over 48 hours after either an abdominoplasty or bunionectomy.1,7
In one study, investigators included patients who were scheduled to undergo a primary unilateral bunionectomy with distal first metatarsal osteotomy and internal fixation under regional anesthesia and were aged 18 to 75 years. The primary outcome included the time-weighted sum of pain intensity difference (SPID) recorded on a numeric pain rating scale (NPRS) of 0 to 48 hours an abdominoplasty without collateral procedures who were aged 18 to 75 years. The primary end point included time-weighted SPID recorded on an NPRS at 0 to 48 hours after the first dose of the study drug. Secondary end points included SPID at 0 to 24 hours after the first dose; the proportion of patients with 30%, 50%, and 70% or greater reduction in pain score at 48 hours; and the number of patients with treatment-related AEs and serious AEs.9
In the bunionectomy trial, there were 274 patients, with 90.1% completing treatment; for the abdominoplasty trial, there were 303 patients, with 81.5% completing treatment. The least-squares mean difference between the high-dose drug and the placebo group was 36.8 and 37.8, respectively. For the lower dose, the results were similar to those of the placebo. Concerning safety, the most common AEs (at least 10%) included nausea, headache, constipation, dizziness, and vomiting for patients in the abdominoplasty trial and nausea and headache for those in the bunionectomy trial.9
“The potential drug interactions of suzetrigine are highlighted by CYP450 3A concerns, which…include one of the most frequent drug interaction concerns of the CYP450 3A4 enzyme. Clinicians will need to review a patient’s medication list prior to utilization, just as with any other additional or new medication for a patient,” Garofoli added.
THE PHARMACIST'S ROLE IN THE OPIOID CRISIS
Pharmacists can play various roles in substance use disorder for patients. Because of their position in the health care system, pharmacists can screen for diversion, monitor for OUD, and educate patients on opioid-related risks. Pharmacists are essential in checking prescriptions for appropriateness and screening for potentially forged or altered prescriptions. Their role also includes educating patients and openly communicating with patients and physicians.10
Pharmacists can discuss opioid-related safety, including adverse effects; legal requirements for refills; and proper use, storage, and disposal. Discussion on disposal and storage is critical when communicating with patients, as many misused prescriptions are obtained from friends or relatives, and not all patients receive proper information about disposing of the medications.10
“Medication storage education is paramount, yet medication disposal education is also important. However, clinicians need to hear patients out,” Garofoli said. “Our health care system is so very complicated that one should take pause [at] the reality that it’s rather hard to [obtain] a prescription pain medication these days, any of them, beyond OTCs, and if a patient is not actually willing to dispose of their pain medication for fear of having to navigate the system in the future to simply attain pain relief, that’s a real raw reality that must be at least acknowledged."
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REFERENCES
1. FDA approves novel nonopioid treatment for moderate to severe acute pain. News release. FDA. January 30, 2025. Accessed February 12, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain
2. Meara K. What pharmacists need to know about suzetrigine for pain management. Drug Topics. February 11, 2025. Accessed February 18, 2025. https://www.drugtopics.com/view/what-pharmacists-need-to-know-about-suzetrigine-for-pain-management
3. The opioid crisis in the United States: a brief history. Congressional Research Service. November 30, 2022. Accessed February 12, 2025. https://crsreports.congress.gov/product/pdf/IF/IF12260
4. Focus on broadband and opioids. Federal Communications Commission. Accessed February 12, 2025. https://www.fcc.gov/reports-research/maps/connect2health/focus-on-opioids.html
5. Increased use of telehealth services and medications for opioid use disorder during the COVID-19 pandemic associated with reduced risk for fatal overdose. News release. CDC. March 29, 2023. Accessed February 12, 2025. https://www.cdc.gov/media/releases/2023/p0329-covid-opioids.html
6. Understanding the opioid overdose epidemic. CDC. November 1, 2024. Accessed February 12, 2025. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html
7. Jones J, Correll DJ, Lechner SM, et al; VX21-548-101 and VX21-548-102 Trial Groups. Selective inhibition of NaV1.8 with VX-548 for acute pain. N Engl J Med. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870
8. A study evaluating efficacy and safety of VX-548 for acute pain after a bunionectomy. ClinicalTrials.gov. Updated February 27, 2023. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT04977336
9. A study evaluating efficacy and safety of VX-548 for acute pain after an abdominoplasty. ClinicalTrials.gov. Updated December 27, 2024. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT05034952
10. Bach P, Hartung D. Leveraging the role of community pharmacists in the prevention, surveillance, and treatment of opioid use disorders. Addict Sci Clin Pract. 2019;14(1):30. doi:10.1186/s13722-019-0158-0
