What EKG (electrocardiogram) changes are associated with Suzetrigine?

EKG Changes Associated with Suzetrigine

According to the FDA drug label, at 2 times the exposure of the maximum recommended Suzetrigine dose, clinically significant QTc prolongation was not observed. 1

Cardiac Electrophysiology Profile

• Suzetrigine is a selective blocker of the NaV1.8 voltage-gated sodium channel, which is primarily expressed in peripheral sensory neurons, not cardiac tissue 1, 2
• Unlike many other medications that can cause QT prolongation, Suzetrigine does not demonstrate clinically significant QTc interval prolongation at therapeutic doses or even at twice the maximum recommended dose 1
• The drug's mechanism of action focuses on peripheral pain pathways rather than affecting cardiac ion channels that typically lead to ECG changes 1, 2

Comparison with Other Medications Known to Cause ECG Changes

• Unlike antiarrhythmic agents, methadone, and haloperidol which are high-risk drugs for QT prolongation and Torsades de Pointes (TdP), Suzetrigine appears to have minimal cardiac effects 3
• Many medications that affect cardiac conduction require specific ECG monitoring protocols, such as dofetilide and sotalol which require baseline and follow-up ECG testing 3
• Some antibiotics like erythromycin are known to prolong the QTc interval and require ECG monitoring during infusion, particularly in critically ill patients 4

Risk Assessment for QTc Prolongation

• Normal QTc values are <430 ms for males and <450 ms in females, with values >500 ms or increases >60 ms from baseline significantly increasing the risk of torsades de pointes 3
• Risk factors for QTc prolongation include female gender, electrolyte abnormalities (particularly hypokalemia and hypomagnesemia), bradycardia, heart failure, and concomitant use of other QT-prolonging medications 3
• The absence of Suzetrigine from lists of QT-prolonging medications suggests it has a favorable cardiac safety profile compared to many psychotropic and pain medications 5

Clinical Implications

• Based on the available evidence, routine ECG monitoring is likely not necessary when initiating Suzetrigine therapy in patients without pre-existing cardiac conditions 1
• Suzetrigine may represent a safer alternative to opioids and other analgesics that have known cardiac effects, particularly for patients with pre-existing QT prolongation or other cardiac risk factors 6, 7
• Unlike tricyclic antidepressants, which can cause significant ECG changes including QRS widening, PR prolongation, and QT prolongation, Suzetrigine appears to have minimal impact on cardiac conduction 8

Monitoring Recommendations

• Standard monitoring practices for medications without significant QTc effects would apply to Suzetrigine 1
• For patients with multiple risk factors for QTc prolongation who are taking Suzetrigine, consider baseline ECG as a precautionary measure, though this is not specifically required by the drug label 3
• If a patient on Suzetrigine develops symptoms suggesting cardiac arrhythmias (syncope, palpitations), an ECG should be obtained to rule out QT prolongation or other conduction abnormalities 3

In summary, Suzetrigine appears to have a favorable cardiac safety profile with minimal to no significant ECG changes at therapeutic doses. This makes it a potentially valuable option for pain management, particularly in patients with cardiac risk factors or those taking other medications that may affect cardiac conduction.