Suzetrigine and Bleeding Risk
Suzetrigine does not appear to carry significant bleeding risk based on available evidence from Phase 3 trials, as it is a selective NaV1.8 sodium channel inhibitor with no antiplatelet or anticoagulant properties, and adverse events in clinical trials were predominantly mild to moderate without notable bleeding complications. 1, 2
Mechanism and Bleeding Profile
Suzetrigine works by selectively inhibiting the voltage-gated sodium channel 1.8 (NaV1.8), which is a completely different mechanism from medications that cause bleeding (anticoagulants, antiplatelets, or NSAIDs). 1, 2
The drug does not bind to other sodium channels or receptors with CNS activity, meaning it lacks the systemic effects that could theoretically impact coagulation pathways. 2
In the two large Phase 3 randomized controlled trials involving 2,191 patients with post-surgical acute pain (abdominoplasty and bunionectomy), adverse events were similar to those seen in typical postsurgical settings, with most being mild to moderate in severity. 1
A Phase 3 single-arm study of 256 participants with various surgical and non-surgical acute pain conditions showed that most adverse events were mild (27.7%) or moderate (8.2%), with no specific mention of bleeding complications. 2
Key Distinctions from Bleeding-Risk Medications
Suzetrigine is fundamentally different from medications that do carry bleeding risk:
Unlike NSAIDs, which increase bleeding risk through antiplatelet effects and loss of GI protection, suzetrigine has no antiplatelet activity. 3
Unlike anticoagulants (warfarin, DOACs, heparins), which directly affect the coagulation cascade and carry significant bleeding risk (2-5% yearly for major bleeding), suzetrigine does not interfere with clotting mechanisms. 4, 5
Unlike SSRIs, which cause platelet dysfunction and increase bleeding risk (especially when combined with NSAIDs, with OR 2.14), suzetrigine does not affect serotonin reuptake or platelet function. 3, 6
Clinical Implications
No special bleeding precautions are needed when prescribing suzetrigine, as it does not share the bleeding risk profile of traditional analgesics like NSAIDs or the anticoagulant/antiplatelet medications discussed in cardiovascular guidelines. 1, 2
Suzetrigine can be considered for patients who might otherwise be at high bleeding risk with NSAIDs or opioids, though this specific population has not been explicitly studied. 1, 2
The drug was well-tolerated across diverse acute pain conditions without the safety concerns that necessitate bleeding risk stratification with anticoagulants or antiplatelet agents. 2
Standard post-surgical bleeding monitoring remains appropriate, but this relates to the surgical procedure itself rather than any pharmacologic effect of suzetrigine. 1