Suzetrigine: A Novel Nonopioid Analgesic Approved by the FDA!!

1. Suzetrigine – Development Rationale

As the opioid addiction and abuse issue worsens, the need for alternate acute pain therapy with a novel mechanism of action has grown. Drug developers have long studied pain-associated NaV, or voltage-gated sodium channel, which transmits pain signals. These channels conduct electrical signals called action potentials in peripheral pain-sensing neurons.¹

Three of the nine subtypes of mammalian NaV—NaV1.7, NaV1.8, and NaV1.9—have been recognized as possible pain targets. Out of these three, NaV1.8 is the most specifically expressed in pain receptors, which convey pain signals to peripheral sensory neurons. Therefore, it is predicted that a treatment that selectively inhibits NaV1.8 channels could mainly decrease pain signal transmission in peripheral sensory nerves without influencing processes mediated by other NaV family members.²

Based on this concept, Suzetrigine was developed as a highly potent and selective inhibitor of the NaV1.8 pain-signaling pathway in the peripheral nervous system.² On January 30, 2025, the US FDA approved Suzetrigine 50 mg tablets (Brand Name Journavx, Vertex Pharmaceuticals), a first-in-class nonopioid analgesic for treating adults with moderate-to-severe acute pain.³

The approval of Suzetrigine was backed by data from two Phase 3 randomized, double-blind, placebo-controlled trials. More than 2,000 patients with moderate to severe pain following abdominoplasty or bunionectomy participated in the trial; Suzetrigine offered pain reduction that was comparable to that of an acetaminophen–opioid combination. The therapy was well-tolerated and safe.¹

2. Suzetrigine – Key Highlights

First in class of non-opioid analgesics.³
Novel mechanism of action. ²
No evidence of addictive potential.²
Clinical studies demonstrated efficacy in postsurgical pain relief.⁴

3. Suzetrigine – Limitations

Long-term safety profile data is lacking.⁴
Extensive post-marketing surveillance is required.⁴
Not all clinical trial results have been as promising.⁴

4. Suzetrigine – Dosage and Administration

Starting dose- 100 mg orally empty stomach at least 1 hour before or 2 hours after food.⁵
Follow-up dose (12 hrs. after first dose) – 50 mg orally every 12 hours with or without food.⁵
Duration of use- Not recommended beyond 14 days.⁵

5. Suzetrigine – Adverse Reactions

The most common adverse reactions reported in clinical trials were itching, muscle spasms, increased creatine phosphokinase, and rash.⁵

6. Suzetrigine – Precautions

Avoid food or drink containing grapefruit during treatment.⁵
Avoid use in patients with severe hepatic impairment.⁵
Lower dose is recommended in patients with moderate hepatic impairment.⁵
- First dose- 100 mg orally empty stomach at least 1 hour before or 2 hours after food
- Second to fourth dose-12 hours after the first dose, 50 mg orally every 12 hours with or without food
- Fifth and successive doses– Start 12 hours after the fourth dose, 50 mg orally every 24 hours with or without food
Concomitant use with strong CYP3A inhibitors is contraindicated.⁵