Suzetrigine Utilization for Postoperative Pain Following Orthopedic surgery: A Retrospective Study

Maaz Shah Khan MBBS, MD¹, Junying Wang PhD¹, William Chan MEng¹, Tina Chen BS¹, Jashvant Poeran MD PhD¹, Jawad N. Saleh PharmD², Daniel Maalouf MD, MPH¹, Jiabin Liu MD, PhD^1,3, Stavros Memtsoudis MD, PhD^1,3, Meghan Kirksey MD, PhD^1,3, Dae Kim MD^1,3, Mary Kelly DNP¹, Faye Rim MD^1,3, Alexandra Sideris PhD^1,3 

¹ Pain Prevention Research Center Department of Anesthesiology, Critical Care & Pain Management, Hospital for Special Surgery, New York, NY, USA

² Pharmacy Department, Clinical Services, The Hospital for Special Surgery, New York, NY, USA

³ Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA

 

 

Introduction

Suzetrigine, the first non-opioid analgesic introduced since celecoxib, is a first-in class medication that selectively blocks voltage-gated sodium Na_v1.8 channels on peripheral nociceptors, sparing central nervous system effects commonly associated with opioids^1,2. Despite U.S. Food and Drug Administration (FDA) approval in January 2025, post-market data remain limited. This study aimed to characterize early clinical use of Suzetrigine for postoperative pain following orthopedic surgery by summarizing patient and case characteristics and quantifying adverse events (AE).

Materials and Methods

Suzetrigine was approved for use in surgical patients at Hospital for Special Surgery (HSS) by the Pharmacy and Therapeutics Committee in April 2025. Administrations are restricted to orders managed by the HSS Perioperative Pain Service (POPS)³. After IRB approval (IRB#2021-1899 and IRB#2025-1169), we retrospectively reviewed electronic health records from 04/18/25 through 10/30/25 for patients receiving Suzetrigine and managed by the POPS team. Data extracted included patient and case characteristics, suzetrigine details such as whether the patient was given Suzetrigine prior to the hospital visit, during hospital stay or continued post-discharge, adverse events/reasons for discontinuation, and patient requests for refills. In parallel, data from the FDA Adverse Event Reporting System (FAERS)⁴ from 01/30/2025 to 10/02/2025 were collected to compare with our findings.

Results/Case Report

There were 103 patients for whom a Suzetrigine prescription was ordered for acute pain management through the POPS service; overall, 62.1% were female, 86.4% were Caucasian, 95.1% represented ASA physical status II/III, 24.3% were chronic opioid users, 42.7% had a history of uncontrolled pain, and 9.7% had a history of substance use. Most patients underwent joint arthroplasty (49.5%), followed by spine surgery (29.1%);

Among n=94 patients who received Suzetrigine during hospitalization, 9.5% also had a preoperative prescription, and 81.9% received a prescription at discharge to complete the 2-week dosing schedule. From the main cohort (n=103), 9.7% requested a refill. During admission, 8 patients (7.8%) experienced at least one AE likely attributable to or exacerbated by Suzetrigine, resulting in medication discontinuation. AEs included agitation, allergic reaction, delirium, nausea, elevated ALT/AST, pruritis, and malaise/brain fog (Table 1). Among 33 patients who discontinued Suzetrigine early, one patient refused the medication, one discontinued due to intolerance, and two discontinued because of no perceived benefit. Suzetrigine discontinuation reasons for 21 patients were not explicitly documented.

In the FAERS database, out of 411 reported cases, 27.7% of adverse reactions reported were allergic reactions, 9.7% reported nausea, 3.4% reported brain fog, and 1.9% reported agitation (Table 2).

Discussion

At our institution, Suzetrigine was approved for inpatient administration to patients after major orthopedic surgery for whom standard multimodal strategies were insufficient. Our initial institutional experiences revealed that these patients generally tolerated Suzetrigine well, though 7.8% reported an AE that resulted in medication discontinuation. All AEs, except for delirium, were also reported in FAERS.  Further, study is necessary, and clinicians should remain vigilant while prescribing this novel agent.

Table 1. Suzetrigine administration details

		N (%)
Prescription prior to hospital admission	No	85 (82.5)
	Yes	18 (17.5)
Given In-hospital	No	9 (8.7)
	Yes	94 (91.3)
Continued outpatient	No	17 (16.5)
	Yes	86 (83.5)
Reason for discontinuation* (N = 33);	Agitation	2 (6.1)
	Delirium	1 (3.0)
	Nausea	3 (6.1)
	Elevated ALT/AST	1 (3.0)
	Patient reported no benefit	2 (6.1)
	Unable to tolerate	1 (3.0)
	Pruritis in throat and chin	1 (3.0)
	Refused medication	1 (3.0)
	Stopped due to feeling sick, off balance, brain fog	1 (3.0)
	Unclear**	21 (63.6)
Refill request	No	93 (90.3)
	Yes	10 (9.7)

* some patients experienced multiple AE

** Includes undocumented reasons for nonuse, unclear ongoing use, or unexpired prescriptions

 

 

Table 2. Distribution of Reported Adverse Events Associated with Suzetrigine by Reaction Group (FAERS, January–October 2025) (N=411)

Reaction group	Adverse reaction	N (%)
Neurological/ophthalmic
	Brain fog/Cognitive disorder/Mental impairment	14 (3.4)
Psychiatric
	Agitation/Anxiety/Jittery/Panic attack/restlessness	8 (1.9)
Gastrointestinal/Hepatic/Nutrition
	Nausea/Vomiting	40 (9.7)
Dermatalogic/Allergic
	Pruritis/ Urticaria/Erythemal rash/Hypersensitivity/Anaphylaxis/Other	114 (27.7)

 

 

 

References:

1.            Courtney D, Potru S, Mathew P. Suzetrigine: A novel selective sodium channel inhibitor for pain. American Journal of Health-System Pharmacy. 2025:zxaf219.

2.            Sideris A, Richman D, Malhotra A, et al. EP132 Initial prescribing practices of suzetrigine for patients with chronic pain. BMJ Publishing Group Ltd; 2025.

3.            Rim F, Liu SS, Kelly M, Kim D, Sideris A, Langford DJ. Preoperative pain screening and optimisation by a perioperative pain service to support complex surgical patients: no patient left behind. British Journal of Anaesthesia. 2024;132(2):437–439.

4.            Liu P, Zhang Y, Xu X, Zhou M, Fei Y, Zhang L. Mining and analysis of adverse drug reactions associated with perampanel based on FAERS database. Epilepsy & Behavior. 2023;145:109283.