This is a prospective, randomized study. The purpose of this study is to evaluate if the addition of Suzetrigine, a new pain medication, to well established peri-operative pain regimen used for total knee replacement surgery will effect pain control.

1. Does Suzetrigine given pre-operatively decrease the total opioid consumed after total knee replacement surgery?
2. Dose Suzetrigine given pre-operatively decrease the visual analog pain scale pain scores after total knee replacement surgery? Study participants will be randomly assigned to receive either Suzetrigine medication or placebo medication.

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all of the following criteria:

• Adults 18-85 years old
• Scheduled to undergo total knee replacement surgery
• All genders

Exclusion Criteria:

Any individual who meets any of the following criteria will be excluded from participation in this study:

• American Society of Anesthesiology Physical Classification (ASA) Class V

• Urgent or emergent surgery

• Contraindications to administration of Suzetrigine:

  • Patients who take moderate-to-severe CYP3A inhibitors (such as Ritonavir, Voriconazole, and Clarithromycin)
  • Patients who take moderate-to-severe CYP3A inducers (such as Phenytoin, Carbamazapine, and Rifabutin)
  • Patients with moderate to severe hepatic impairment

• History of substance use disorder or chronic opioid use or alcohol abuse

• Reoperation

• Patient refusal or inability to consent

• Pregnancy

We are not sharing IPD to protect participant privacy, maintaining study integrity, and respecting intellectual property

Pharmacy will be responsible for randomizing study participants to either the treatment arm or placebo (non-treatment) arm. Both treatment and placebo medications will be made to look identical so that only the pharmacy will know which arm the participant was assigned to.