Drug Update · Pain Management

FDA Approves Suzetrigine for Acute Pain: SPID48 48.4 in Abdominoplasty

July 10, 2026

FDA approval date

2025-01-30

Indication

Moderate to severe acute pain, including postoperative pain, in adults

Primary endpoint (abdominoplasty)

SPID48 LS mean difference 48.4 versus placebo (95% CI 33.6 to 63.1; P < 0.0001) [1]

Primary endpoint (bunionectomy)

SPID48 LS mean difference 29.3 versus placebo (95% CI 14.0 to 44.6; P = 0.0002) [1]

Dosing (recommended)

Starting dose 100 mg on empty stomach, then 50 mg every 12 hours starting 12 hours after initial dose [8][12]

Clinical Perspective

Clinicians who treat adults with moderate to severe acute pain, including postoperative pain, now have an FDA-approved oral NaV1.8-selective option (suzetrigine/JOURNAVX) to consider for short-term use ^[3]^[2]. The approval is supported by two randomized phase 3 trials showing SPID48 reductions versus placebo after abdominoplasty and bunionectomy, and a faster time to a 2-point pain reduction versus placebo in both surgical models ^[1]^[3]. Key unanswered questions include how suzetrigine compares with other nonopioid analgesics across broader surgical populations and longer postoperative courses beyond the 48-hour primary evaluation window ^[1]^[3].

Dr. Abhishek Malhotra · ENT

The FDA approved suzetrigine (JOURNAVX) tablets for the treatment of moderate to severe acute pain, including postoperative pain, in adults on 2025-01-30 based on two phase 3 randomized, double-blind, placebo- and active-controlled trials showing a reduction in the time-weighted sum of pain intensity difference from 0 to 48 hours (SPID48) versus placebo after abdominoplasty (LS mean difference 48.4; 95% CI, 33.6 to 63.1; P < 0.0001) and after bunionectomy (LS mean difference 29.3; 95% CI, 14.0 to 44.6; P = 0.0002) ^[1]^[3].

Clinical Context

Suzetrigine (brand: JOURNAVX) is an oral, nonopioid small molecule developed by Vertex Pharmaceuticals that selectively inhibits the voltage-gated sodium channel NaV1.8, a channel expressed in peripheral sensory neurons and dorsal root ganglia that transmits pain signals ^[3]^[1]. The FDA indication is for treatment of moderate to severe acute pain, including postoperative pain, in adults; the approval follows two randomized phase 3 trials in postsurgical acute-pain settings (full abdominoplasty and bunionectomy) that compared suzetrigine with placebo and hydrocodone bitartrate/acetaminophen ^[1]^[3]. The product was approved in 2025 and is described in the U.S. prescribing information and DailyMed highlights ^[3]^[2].

Key Findings

In the full abdominoplasty trial (Trial 1), suzetrigine reduced SPID48 by 48.4 versus placebo (LS mean difference 48.4; 95% CI, 33.6 to 63.1; P < 0.0001) ^[1]^[3].
In the bunionectomy trial (Trial 2), suzetrigine reduced SPID48 by 29.3 versus placebo (LS mean difference 29.3; 95% CI, 14.0 to 44.6; P = 0.0002) ^[1]^[3].
Neither trial demonstrated superiority of suzetrigine versus hydrocodone bitartrate/acetaminophen on SPID48 ^[1].
Time to clinically meaningful pain relief (≥ 2-point reduction on the 11-point numeric pain rating scale) occurred earlier with suzetrigine: median 119 minutes versus 480 minutes with placebo after abdominoplasty, and 240 minutes versus 480 minutes with placebo after bunionectomy ^[1]^[3].

These results supported the FDA determination that suzetrigine provides analgesic benefit over placebo in adults with moderate-to-severe acute postoperative pain ^[1]^[3].

Safety & Tolerability

Pruritus ^[2]^[3]
Muscle spasms ^[2]^[3]
Increased blood creatine phosphokinase / CPK elevations (reports of CPK > 3× ULN and increased blood CPK) ^[2]^[3]
Rash ^[2]^[3]
Nausea and vomiting (incidence reported across trials; trial-specific rates described in labeling) ^[2]^[3]
Decreased estimated glomerular filtration rate (eGFR) decreases reported (≥ 25% but < 50% in pooled trials) ^[2]^[3]
Postprocedural hematoma (listed among adverse events leading to discontinuation) ^[2]^[3]
Hypotension and syncope (listed among adverse events leading to discontinuation) ^[2]^[3]

Study Design

The FDA approval was based on two phase 3, randomized, double-blind, placebo- and active-controlled trials in adults with moderate-to-severe acute pain following full abdominoplasty (n = 1,118) and bunionectomy (n = 1,073) that randomized participants to suzetrigine (initial 100 mg dose, then 50 mg every 12 hours), hydrocodone bitartrate/acetaminophen (5/325 mg every 6 hours), or placebo for 48 hours ^[1]^[3]. Clinicians should consult current prescribing information for full dosing guidance. The trials used SPID48 (time-weighted sum of pain intensity difference from 0 to 48 hours) versus placebo as the primary endpoint and included key secondary comparisons versus hydrocodone/acetaminophen ^[1]^[3]. The FDA original approval date is 2025-01-30 ^[3].

FAQ

Q1 What is JOURNAVX (suzetrigine) approved for?

A1 JOURNAVX (suzetrigine) tablets are approved for the treatment of moderate to severe acute pain, including postoperative pain, in adults. The approval was based on two randomized, double-blind, placebo- and active-controlled phase 3 trials in full abdominoplasty and bunionectomy that demonstrated greater reduction in the time-weighted sum of pain intensity difference from 0 to 48 hours (SPID48) versus placebo.

Q2 How does suzetrigine work?

A2 Suzetrigine is a selective inhibitor of the voltage-gated sodium channel NaV1.8, which is expressed in peripheral sensory neurons including dorsal root ganglia and contributes to transmission of pain signals. By selectively blocking NaV1.8, suzetrigine reduces transmission of pain signals to the spinal cord and brain; an active metabolite (M6-SUZ) is less potent than the parent compound.

Q3 What is the recommended dose of JOURNAVX?

A3 The recommended starting oral dose is 100 mg taken on an empty stomach (at least 1 hour before or 2 hours after food). Starting 12 hours after the initial dose, the recommended dosing is 50 mg orally every 12 hours. Doses after the initial period may be taken with or without food. Use has not been studied beyond 14 days; dosage adjustments are specified for moderate hepatic impairment and when coadministered with CYP3A inhibitors. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of JOURNAVX?

A4 The most commonly reported adverse reactions in trials and labeling that occurred more frequently with JOURNAVX than with placebo included pruritus, muscle spasms, increased creatine phosphokinase, and rash. Nausea and vomiting were observed across trials with differing incidence by surgical model. Laboratory findings reported included CPK elevations and decreases in estimated glomerular filtration rate in some patients; postprocedural hematoma, hypotension, and syncope were among events leading to discontinuation in trials.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Suzetrigine for Acute Pain: SPID48 48.4 in Abdominoplasty

FDA Approves Suzetrigine for Acute Pain: SPID48 48.4 in Abdominoplasty

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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