Highlights

See Patient counseling information and medication guide available in the DAILYMED drug label information.

Indications and usage

Suzetrigine is indicated for the treatment of moderate to severe acute pain in adults.

Dosage and administration

Recommended dosage and administration instructions

Swallow suzetrigine tablets whole and do not chew or crush.

The recommended starting dose of suzetrigine is 100 mg orally. Take the starting dose on an empty stomach at least 1 hour before or 2 hours after food to avoid delay in onset of action. Clear liquids may be consumed during this time (eg, water, apple juice, vegetable broth, tea, black coffee).

Starting 12 hours after the initial dose, take 50 mg of suzetrigine orally every 12 hours. Take these doses with or without food.

Avoid food or drink containing grapefruit during treatment with suzetrigine.

Use suzetrigine for the shortest duration, consistent with individual patient treatment goals. Use of suzetrigine for the treatment of moderate to severe acute pain has not been studied beyond 14 days.

Recommended dosage in patients with hepatic impairment

The recommended dosage of suzetrigine in patients with hepatic impairment is described in Table 1.

Table 1. Recommended Suzetrigine Dosage in Patients with Hepatic Impairment

Dosage modifications for CYP3A inhibitors

Suzetrigine is contraindicated in patients taking strong CYP3A inhibitors. When suzetrigine is administered to patients taking moderate CYP3A inhibitors, reduce the suzetrigine dose as described below:

Dose 1. The recommended starting dose of suzetrigine is 100 mg orally. Take the starting dose on an empty stomach at least 1 hour before or 2 hours after food. Clear liquids may be consumed during this time (eg, water, apple juice, vegetable broth, tea, black coffee).

Doses 2, 3, and 4. Starting 12 hours after the initial dose, take 50 mg of suzetrigine orally every 12 hours. Take these doses with or without food.

Dose 5 and subsequent doses. Starting 12 hours after Dose 4, take 50 mg of suzetrigine orally every 24 hours. Take these doses with or without food.

Avoid food or drink containing grapefruit during treatment with suzetrigine.

Recommendations regarding missed doses

For patients on the standard recommended dosing schedule:

For patients with moderate hepatic impairment or patients taking moderate CYP3A inhibitors, if a dose is missed, take the missed dose as soon as possible. If the next scheduled dose is within 6 hours, skip the next scheduled dose and take the subsequent doses at the recommended time.

Dosage forms and strengths

Tablets: 50 mg, blue, film-coated, oblong tablets debossed with "VX50" on one side and plain on the other.

Contraindications

Concomitant use of suzetrigine with strong CYP3A inhibitors is contraindicated.

Warnings and precautions

Increased risk of adverse reactions with concomitant use with strong or moderate CYP3A inhibitors

Strong and moderate CYP3A inhibitors increase suzetrigine and M6-SUZ (active metabolite) exposures, which may cause suzetrigine adverse reactions. Concomitant use of suzetrigine with strong CYP3A inhibitors is contraindicated. Reduce the suzetrigine dosage with moderate CYP3A inhibitors.

Risk of drug interactions with certain CYP3A substrates

Suzetrigine is an inducer of CYP3A. If suzetrigine is used concomitantly with sensitive CYP3A substrates or CYP3A substrates where minimal concentration changes may lead to loss of efficacy, refer to the Prescribing Information for the CYP3A substrates for dosing instructions. Dosage adjustment of the concomitant CYP3A substrates may be required when initiating or discontinuing suzetrigine.

Risk of drug interactions with certain hormonal contraceptives

Suzetrigine-treated patients taking concomitant hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use additional nonhormonal contraceptives (such as condoms) or use alternative contraceptives (eg, a combined oral contraceptive containing ethinyl estradiol as the estrogen and levonorgestrel or norethindrone as the progestin, an intrauterine system) during suzetrigine treatment and for 28 days after discontinuation of suzetrigine.

Risk of adverse reactions in patients with moderate and severe hepatic impairment

Patients with moderate hepatic impairment have higher systemic exposures of suzetrigine and M6-SUZ (active metabolite) than those with normal hepatic function, which may increase the risk of suzetrigine-related adverse reactions.

Avoid use of suzetrigine in patients with severe hepatic impairment (Child-Pugh Class C). The recommended suzetrigine dosage is lower in patients with moderate hepatic impairment (Child-Pugh Class B) than in those with normal hepatic function.

Adverse reactions

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety profile of suzetrigine is primarily based on data from the pooled, double-blind, placebo- and active-controlled trials in 874 adult patients with moderate to severe acute pain following full abdominoplasty (Trial 1) and bunionectomy (Trial 2), with supportive safety data from one single arm trial in 256 adult patients with moderate to severe acute pain in a broad range of acute pain conditions (Trial 3).

In Trials 1 and 2, 874 patients received at least one dose of suzetrigine. The proportion of patients in Trials 1 and 2 who discontinued study drug prematurely due to adverse events was:

The safety profile of suzetrigine was also evaluated by the following subgroup analyses: age (≥ 18 to < 65 years and ≥ 65 years), sex, and race. Because most patients enrolled in the clinical trials were ≥ 18 to < 65 years of age, female, and white, there were insufficient data to detect differences in safety signals between these subgroups.

Table 2 displays adverse reactions that occurred more frequently in suzetrigine-treated patients than placebo-treated patients in the pooled Trials 1 and 2.

Table 2. Adverse Reactions Reported in ≥1% of Suzetrigine-Treated Patients and Greater than Rate of Placebo in Two 48-hour Trials in Moderate to Severe Acute Pain (Trials 1 and 2, Pooled)

Nausea and vomiting. In Trial 1, the incidence of patients who experienced either nausea or vomiting was 20% in suzetrigine-treated patients, 33% in HB/APAP-treated patients, and 25% in placebo-treated patients. In Trial 2, the incidence of patients who experienced either nausea or vomiting was 9% in suzetrigine-treated patients, 16% in HB/APAP-treated patients, and 12% in placebo-treated patients.

Laboratory abnormalities.

Creatine phosphokinase elevations. In Trials 1 and 2, 2.9% of suzetrigine-treated patients and 1.2% of placebo-treated patients had a creatine phosphokinase (CPK) level > three times the upper limit of normal. The incidence of increased blood CPK was 1.1% in suzetrigine-treated patients and 0.5% in placebo-treated patients. All reports of CPK elevations occurred in the post-surgical setting. There were no associated signs or symptoms, no serious adverse reactions, and no patients required treatment discontinuation or interruption.

Decreased estimated glomerular filtration rate. In Trials 1 and 2, 2.5% of suzetrigine-treated patients and 0.9% of placebo-treated patients had a decrease in estimated glomerular filtration rate (eGFR) of ≥ 25% but < 50%. Follow-up eGFR data for these controlled trials were not available after treatment discontinuation. Similar decreases in eGFR also occurred in Trial 3 (the open-label Phase 3 study) and appeared to resolve to baseline by the final safety follow-up visit. There was no control arm for comparison. There were no adverse reactions of eGFR decrease in suzetrigine-treated patients.

Adverse reactions from the open-label study (Trial 3). In an open-label study of patients with moderate to severe acute pain following a surgical procedure or nonsurgical condition (NCT05661734), a total of 256 adult patients received at least one dose of suzetrigine. Patients received 100 mg as a first dose, then 50 mg every 12 hours, and continued to receive suzetrigine for up to 14 days or until their pain resolved. Rescue medication of 650 mg of acetaminophen and 400 mg of ibuprofen together every 6 hours was permitted as needed for pain relief. The patients' perceptions of pain control were captured by patient global assessment (PGA). The mean duration of treatment with suzetrigine was 9.6 days. The majority of patients were female (68%), and the median age was 43 years (range: 18 to 78).

In Trial 3, a total of 222 (87%) patients received suzetrigine for post-surgical pain; orthopedic surgery was the most common (eg, ligament operation, arthrodesis), followed by plastic surgery (eg, liposuction, mammoplasty), otorhinolaryngologic surgery (eg, nasal septal operation, turbinoplasty), and general and urologic surgery (eg, inguinal hernia repair). Thirty-four (13%) patients received suzetrigine for nonsurgical pain (eg, arthralgias, limb pain, and sprains/strains).

The proportion of patients who discontinued the study drug prematurely was 2% due to adverse events (arrhythmia [0.4%], nausea [0.4%], somnolence [0.4%], rash [0.4%]) and 1.6% due to lack of efficacy.

The safety profile of suzetrigine in Trial 3 was consistent with that observed in Trials 1 and 2.

Drug interactions

Effect of other drugs on suzetrigine

Table 3 describes drug interactions where concomitant use of another drug affects the use of suzetrigine.

Table 3. Drug Interactions: Concomitant Use of Other Drugs that Affect the Use of Suzetrigine

Effect of suzetrigine on other drugs

CYP3A substrates. If suzetrigine is used concomitantly with sensitive CYP3A substrates or CYP3A substrates where minimal concentration changes may lead to loss of efficacy, refer to the Prescribing Information for the CYP3A substrates for dosing instructions. Dosage modification of the concomitant CYP3A substrates may be required when initiating or discontinuing suzetrigine.

Suzetrigine is an inducer of CYP3A. Concomitant use with suzetrigine may reduce the exposure of sensitive CYP3A substrates, which may decrease the efficacy of these substrates. Discontinuation of suzetrigine may increase the exposure of sensitive CYP3A substrates.

Hormonal contraceptives. Suzetrigine-treated patients using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use additional nonhormonal contraceptives (such as condoms) or use alternative contraceptives (such as a combined oral contraceptive containing ethinyl estradiol as the estrogen and levonorgestrel or norethindrone as the progestin, or an intrauterine system) during treatment with suzetrigine and for 28 days after discontinuation of suzetrigine.

Suzetrigine did not result in clinically significant changes in the pharmacokinetics of ethinyl estradiol and levonorgestrel when used concomitantly with an oral contraceptive containing ethinyl estradiol and levonorgestrel.

Use in specific populations

Pregnancy

Risk summary. There are no available data on the use of suzetrigine during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

In animal reproduction studies in rats, effects on implantation and maintenance of pregnancy occurred at oral suzetrigine doses of ≥ 2.2 times the maximum recommended human dose (MRHD) when administered during early embryonic development or throughout organogenesis. In a pre- and postnatal development study, reduced mean gestation length and increased postnatal pup mortality were observed at maternal rat exposures of 1.6 times the MRHD, and decreased rat pup body weights were observed during the period of birth to weaning at maternal exposures of 2.2 times the MRHD. No malformations were observed when suzetrigine was administered orally to rats and rabbits during the period of organogenesis at doses up to 2.2 and 5.9 times, respectively, the MRHD. The clinical relevance of these findings is unclear.

The background risk of major birth defects and miscarriage in patients with moderate to severe acute pain is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data.

Animal data. Suzetrigine was administered orally to pregnant rabbits during the period of organogenesis at 50, 100, and 200 mg/kg/day (approximately 1.6, 3.1, and 5.9 times, respectively, the steady state MRHD exposure based on AUC). Increased post-implantation loss and lower fetal body weight were observed at 200 mg/kg/day, which is a dose that also caused maternal toxicity. No adverse embryofetal effects were observed at doses up to 100 mg/kg.

Suzetrigine was administered orally to pregnant rats during the period of organogenesis at 5, 10, and 15 mg/kg/day (approximately 0.57, 1.6, and 2.2 times, respectively, the steady state MRHD exposure based on AUC). Increased post-implantation loss and a lower number of live fetuses were observed at 15 mg/kg/day. No adverse embryofetal effects were observed at doses up to 10 mg/kg. Placental transfer of suzetrigine was observed in pregnant rats.

In a pre- and postnatal development study, suzetrigine was administered orally to pregnant rats at doses of 5, 10, and 15 mg/kg/day (approximately 0.57, 1.6, and 2.2 times, respectively, the steady state MRHD exposure based on AUC) from Gestation Day 6 through Lactation Day 20. Reduced mean gestation length and increased postnatal pup mortality between birth and Postnatal Day 4 were observed at ≥ 10 mg/kg, and increased incidences of fully resorbed litters, lower live newborn pups, and reductions in pup body weights were observed at 15 mg/kg. No effects on learning and memory or sexual maturation were observed at a dose up to 15 mg/kg/day.

The effects on implantation, maintenance of pregnancy, reduced mean gestation length, and increased postnatal pup mortality in rats are of uncertain relevance to humans.

Lactation

Risk summary. There are no data on the presence of suzetrigine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Suzetrigine is present in animal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for suzetrigine and any potential adverse effects on the breastfed child from suzetrigine or from the underlying maternal condition.

Females and males of reproductive potential

Contraception. Advise patients using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone to use an additional nonhormonal contraceptive or to use alternative contraceptives during suzetrigine treatment and for 28 days after discontinuation of suzetrigine.

Infertility. In a female fertility study in rats, increased pre-implantation loss was observed at oral suzetrigine doses of ≥ 2.2 times the MRHD when administered before mating and through Gestation Day 7. Following discontinuation of suzetrigine for 4 weeks, the increased pre-implantation loss in rats was not observed. The finding in rats may be explained by the effect of suzetrigine on the rat progesterone receptor, which was more sensitive to suzetrigine than the human progesterone receptor, based on in vitro studies. The finding in the rat study is of uncertain relevance to humans.

Suzetrigine may reversibly impact the likelihood of females of reproductive potential to become pregnant while on treatment. Patients using contraceptives should continue to use contraceptives.

Pediatric use

The safety and effectiveness of suzetrigine have not been established in pediatric patients.

Geriatric use

Of the total 1130 patients with moderate to severe acute pain who received suzetrigine in the Phase 3 studies, 71 patients (6.3%) were 65 years of age and older.

Clinical studies of suzetrigine did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, based on population pharmacokinetic analyses in patients, with ages ranging from 18 to 75 years, age does not have a clinically relevant impact on suzetrigine exposure.

Hepatic impairment

Suzetrigine has not been studied in patients with severe hepatic impairment. Avoid use of suzetrigine in patients with severe hepatic impairment (Child-Pugh Class C). The recommended suzetrigine dosage is lower in patients with moderate hepatic impairment (Child-Pugh Class B) than in those with normal hepatic function. The recommended dosage in patients with mild hepatic impairment (Child-Pugh Class A) is the same as in those with normal hepatic function.

Patients with moderate hepatic impairment had greater suzetrigine and M6-SUZ (the active metabolite) exposure than those with normal hepatic function, which may increase the risk of suzetrigine adverse reactions.

Renal impairment

Suzetrigine has not been studied in patients with renal impairment of eGFR < 15 mL/min. Avoid use of suzetrigine in patients with renal impairment of eGFR < 15 mL/min. The recommended dosage in patients with eGFR > 15 mL/min is the same as in those with normal kidney function.

Overdosage

No specific antidote is available for overdose with suzetrigine. Treatment of overdose consists of general supportive measures, including monitoring of vital signs and observation of the clinical status of the patient. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

Clinical pharmacology

Mechanism of action

Suzetrigine is a selective blocker of the NaV1.8 voltage-gated sodium channel, compared to other known voltage-gated sodium channels (NaV1.1 through 1.9). NaV1.8 is expressed in peripheral sensory neurons, including dorsal root ganglion neurons, where its role is to transmit pain signals (action potentials). By selectively inhibiting NaV1.8 channels, suzetrigine inhibits transmission of pain signals to the spinal cord and brain. M6-SUZ, a major active metabolite, is a less potent inhibitor of NaV1.8 than suzetrigine by 3.7-fold.

Pharmacodynamics

Cardiac electrophysiology. At two times the exposure of the maximum recommended suzetrigine dose, clinically significant QTc prolongation was not observed.

Pharmacokinetics

The pharmacokinetic parameters for suzetrigine and its major active metabolite, M6-SUZ, are shown in Table 4.

Table 4. Pharmacokinetic Parameters of Suzetrigine and M6-SUZ

Effect of food. Administration of 100 mg of suzetrigine (the first dose) with a high-fat meal (800 to 1000 calories, 50% derived from fat), a moderate-fat meal (600 calories, 30% derived from fat), and a low-fat meal (up to 500 calories with no more than 25% derived from fat) resulted in decreased initial concentrations of suzetrigine and M6-SUZ in comparison to a fasted state. The median T_max of suzetrigine and M6-SUZ in the fasted state was 3 hours and 8 to 10 hours, respectively. When administered in the fed state (high-fat meal or moderate-fat meal), the median T_max of suzetrigine was delayed to 5 hours, and the median T_max of M6-SUZ was delayed to 24 hours. The C_max and AUC of suzetrigine and M6-SUZ were not affected by any of the meal conditions, including a high-fat meal consumed one hour after suzetrigine administration.

Administration of the second suzetrigine dose of 50 mg with or without regard to meals is predicted not to affect the systemic exposures of suzetrigine and M6-SUZ.

Specific populations. No clinically significant differences in pharmacokinetics of suzetrigine and M6-SUZ were observed based on age (18-75 years), sex, body weight (44-126 kg), race, and renal impairment (eGFR ≥ 15 mL/min by CKD-EPI equation with adjustment for the body surface area). The effect of renal impairment with eGFR < 15 mL/min on suzetrigine and M6-SUZ pharmacokinetics is unknown.

Patients with hepatic impairment. In patients with mild hepatic impairment (Child-Pugh Class A), no clinically significant differences in pharmacokinetics of suzetrigine and M6-SUZ were observed. In patients with moderate hepatic impairment (Child-Pugh Class B), at steady state, suzetrigine AUC0-12h increased by 1.5-fold (90% CI: 1.1-2.1) and C_max increased by 1.3-fold (90% CI: 1.0-1.7) and M6-SUZ AUC0-12h and C_max both increased by 1.2-fold (AUC 90% CI: 0.83-1.6; C_max 90% CI: 0.84-1.6). The effect of severe hepatic impairment (Child-Pugh Class C) on suzetrigine and M6-SUZ pharmacokinetics is unknown.

Drug interaction studies.

Clinical studies and model-informed approaches.

Strong CYP3A inhibitors. Concomitant administration of itraconazole (a strong CYP3A inhibitor) with a single dose of suzetrigine increased the geometric mean (90% CI) AUC0-inf of suzetrigine and M6-SUZ by 4.8-fold (4.3-5.4) and 4.4-fold (3.6-5.4), respectively, while the geometric mean (90% CI) C_max of suzetrigine increased by 1.5-fold (1.3-1.6) and C_max of M6-SUZ decreased by 32% (24% to 39%).

Moderate CYP3A inhibitors. Concomitant administration of fluconazole (a moderate CYP3A inhibitor) with suzetrigine with the recommended dosage modification is predicted to increase the geometric mean (90% CI) AUCtau of suzetrigine and M6-SUZ by 1.5-fold (1.4-1.5) and 1.2-fold (1.2-1.3), respectively, while the geometric mean (90% CI) C_max of suzetrigine and M6-SUZ is predicted to increase by 1.4-fold (1.4-1.5) and 1.1-fold (1.1-1.2), respectively, when compared to the regular recommended dosage in the absence of fluconazole.

Strong CYP3A inducers. Concomitant administration of rifampin (strong CYP3A inducer) at steady state with a single dose of suzetrigine decreased the geometric mean (90% CI) AUC0-inf of suzetrigine and M6-SUZ by 93% (91% to 94%) and 85% (83% to 86%), respectively, while the geometric mean (90% CI) C_max of suzetrigine decreased by 80% (75-83%) and the C_max of M6-SUZ increased by 1.3-fold (1.1-1.5).

Moderate CYP3A inducers. Concomitant administration of efavirenz (moderate CYP3A inducer) with a single dose of suzetrigine is predicted to decrease the geometric mean (90% CI) AUC0-t of suzetrigine and M6-SUZ by 63% (61% to 65%) and 60% (58% to 62%), respectively, while the geometric mean (90% CI) C_max of suzetrigine is predicted to decrease by 29% (27% to 32%) and M6-SUZ is predicted to increase by 1.3-fold (1.3 to 1.4), respectively.

Sensitive CYP3A substrate.: Suzetrigine, administered 50 mg every 12 hours, at steady state, decreased the geometric mean (90% CI) AUC0-inf of midazolam (sensitive CYP3A substrate) by 48% (43% to 53%) and C_max by 37% (27% to 45%).

Proton pump inhibitors. No clinically significant differences in suzetrigine and M6-SUZ pharmacokinetics were observed when suzetrigine was used concomitantly with omeprazole.

Other drugs. No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with suzetrigine: oral digoxin (P-gp substrate), ethinyl estradiol (hormonal contraceptive), or levonorgestrel (hormonal contraceptive).

In vitro studies.

Cytochrome P450 (CYP450) enzymes. Suzetrigine inhibits CYP2C8, CYP2C9, and CYP2C19, but is not expected to result in clinically significant drug interactions. Suzetrigine does not inhibit CYP1A2, CYP2B6, CYP2D6, and CYP3A enzymes, and M6-SUZ does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A enzymes. Suzetrigine induces CYP3A and, to a lesser extent, CYP2B6, CYP2C8, CYP2C9, and CYP2C19. Suzetrigine does not induce CYP1A2.

UDP-glucuronosyltransferase (UGT). Suzetrigine does not inhibit UGT1A1.

Transporter systems. Suzetrigine and M6-SUZ are not substrates of BCRP, OATP1B1, or OATP1B3. Suzetrigine is not a P-gp substrate, but M6-SUZ is a P-gp substrate. Suzetrigine inhibits OATP1B1, OATP1B3, and OAT3 but is not expected to result in clinically significant drug interactions. Suzetrigine does not inhibit BCRP, OAT1, OCT2, MATE1, and MATE2/K transporters. M6-SUZ inhibits OATP1B1, OATP1B3, OAT1, and OAT3 but is not expected to result in clinically significant drug interactions. M6-SUZ does not inhibit P-gp, BCRP, OCT2, MATE1, and MATE2/K transporters.

Nonclinical toxicology

Carcinogenesis, mutagenesis, and impairment of fertility

Carcinogenesis. Long-term animal studies have not been completed to evaluate the carcinogenic potential of suzetrigine.

Mutagenesis. Suzetrigine was not mutagenic in the bacterial reverse mutation assay (Ames test), or clastogenic in the in vitro micronucleus assay with a human TK6 lymphoblastoid cell line, or in the in vivo rat bone marrow micronucleus assay.

Impairment of fertility. In a female fertility study, female rats were treated orally with suzetrigine at 5, 10, and 15 mg/kg/day for a minimum of 14 days prior to mating, throughout mating, and through Gestation Day 7. These doses are approximately 0.57, 1.6, and 2.2 times the steady state MRHD exposure based on AUC. Increased pre-implantation loss was observed at 15 mg/kg (approximately 2.2 times the MRHD based on AUC). The finding in rats may be explained by the effect of suzetrigine on the rat progesterone receptor, which was more sensitive to suzetrigine than the human progesterone receptor, based on in vitro studies. Following a 4-week withdrawal of treatment, there were no effects on female fertility and early embryonic development. The finding in the rat study is of uncertain relevance to humans.

In a male fertility study, male rats were treated orally with suzetrigine at 200, 600, and 1000 mg/kg/day for a minimum of 28 days prior to mating and through mating. These doses are 3.6, 9.7, and 13.8 times the steady state MRHD exposure based on AUC, respectively. Suzetrigine had no effects on sperm parameters (motility, concentration, or morphology), reproductive performance, or uterine parameters (number of implants, viable implants, pre-implantation loss, early resorptions, and post-implantation loss) at any dose.

Clinical studies

Overview of clinical studies

The efficacy of suzetrigine in the treatment of moderate to severe acute pain in adults was established in two randomized, double-blind, placebo and active-controlled trials of acute pain, one following full abdominoplasty (Trial 1) and the other following bunionectomy (Trial 2). In each trial, pain intensity was measured using a patient-reported 11-point numeric pain rating scale (NPRS), ranging from 0 to 10, where zero corresponds to no pain and 10 corresponds to the worst pain imaginable.

Patients were eligible for study participation if they had moderate to severe pain on the verbal categorical rating system (VRS) and a pain score of ≥ 4 on the NPRS, within 4 hours of the abdominoplasty completion (Trial 1) or during the 9-hour period after discontinuation of regional anesthesia following bunionectomy (Trial 2). Once eligible, patients were randomized to receive oral suzetrigine, placebo, or hydrocodone bitartrate/acetaminophen (HB/APAP) for a duration of 48 hours. For the suzetrigine treatment regimen, patients received an initial loading dose of 100 mg suzetrigine, followed by 50 mg every 12 hours. For the HB/APAP-control regimen, patients received 5 mg/325 mg every 6 hours. For both studies, 400 mg of ibuprofen every 6 hours, as needed for pain relief, was permitted as a rescue medication.

Moderate to severe acute pain following full abdominoplasty

Trial 1 (NCT05558410) evaluated the efficacy of suzetrigine over 48 hours in 1,118 adult patients with moderate to severe acute pain following a full abdominoplasty procedure (suzetrigine n = 447, placebo n = 223, and hydrocodone bitartrate/acetaminophen (HB/APAP) n = 448). The majority of patients were female (98%), and the mean age was 42 years (range: 18 to 69). The study population consisted of 70% White participants, 27% Black or African American participants, 1% Asian participants, 0.8% Native Hawaiian or other Pacific Islander participants, 0.5% American Indian or Alaska Native participants, and 0.9% Other or Multiracial participants, among which 34% identified as Hispanic or Latino. The mean pain score at baseline was 7.4 (range: 4 to 10). All baseline characteristics, including NPRS, VRS, and BMI, were generally balanced across treatment arms.

In Trial 1, 89% of patients in the suzetrigine group completed the treatment period (compared to 75% of patients in the placebo group and 85% of patients in the HB/APAP group), and 9% of patients in the suzetrigine group discontinued due to lack of efficacy (compared to 22% of patients in the placebo group and 13% of patients in the HB/APAP group).

Efficacy was evaluated by the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) in the suzetrigine group compared to the placebo group and then to the HB/APAP group. Treatment with suzetrigine demonstrated statistically significant superior reduction in pain compared to treatment with placebo (see Table 5).

In an exploratory analysis, the time-weighted sum of the pain intensity difference from 0 to 24 hours (SPID24) reported using the least square mean was 48.0 for the suzetrigine group and 24.2 for the placebo group. The mean pain intensities over time are depicted for the suzetrigine, placebo, and HB/APAP groups in Figure 1 (available in the Clinical studies section of the DAILYMED drug label information).

Table 5. SPID48 Results in Adults with Moderate to Severe Acute Pain Following Full Abdominoplasty (Trial 1)

Time to onset of pain relief. The median time to meaningful pain relief (defined as a ≥ 2-point reduction in NPRS) was 119 minutes for patients in the suzetrigine group and 480 minutes for patients in the placebo group. The median time to onset of perceptible pain relief (defined as a ≥ 1-point reduction in NPRS) for patients in the suzetrigine group was 34 minutes.

Moderate to severe acute pain following bunionectomy

Trial 2 (NCT05553366) evaluated the efficacy of suzetrigine over 48 hours in 1,073 adult patients with moderate to severe acute pain following bunionectomy (suzetrigine n = 426, placebo n = 216, and HB/APAP n = 431). The majority of patients were female (85%), and the mean age was 48 years (range: 18 to 75). The study population consisted of 71% White participants, 24% Black or African American participants, 2% Asian participants, 0.2% Native Hawaiian or other Pacific Islander participants, 1% American Indian or Alaska Native participants, and 1% other or multiracial participants, and 0.3% with race missing, among which 34% identified as Hispanic or Latino. The mean pain score at baseline was 6.8 (range: 4 to 10). All baseline characteristics, including NPRS, VRS, and BMI, were generally balanced across treatment arms.

In Trial 2, 87% of patients in the suzetrigine group completed the treatment period (compared to 82% of patients in the placebo group and 90% of patients in the HB/APAP group), and 12% of patients in the suzetrigine group discontinued due to lack of efficacy (compared to 16% of patients in the placebo group and 8% of patients in the HB/APAP group).

Efficacy was evaluated by the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) in the suzetrigine group compared to the placebo group and then to the HB/APAP group. Treatment with suzetrigine demonstrated statistically significant superior reduction in pain compared to treatment with placebo (see Table 6).

In an exploratory analysis, the time-weighted sum of the pain intensity difference from 0 to 24 hours (SPID24) reported using the least square mean was 30.6 in the suzetrigine group and 19.8 in the placebo group. The mean pain intensities over time are depicted for the suzetrigine, placebo, and HB/APAP groups in Figure 2 (available in the Clinical studies section of the DAILYMED drug label information).

Table 6. SPID48 Results in Adults with Moderate to Severe Acute Pain Following Bunionectomy (Trial 2)

Time to onset of pain relief. The median time to meaningful pain relief (defined as ≥ 2-point reduction in NPRS) was 240 minutes for patients in the suzetrigine group and 480 minutes in the placebo group. The median time to onset of perceptible pain relief (defined as a ≥ 1-point reduction in NPRS) for patients in the suzetrigine group was 60 minutes.

How supplied/storage and handling

Suzetrigine (suzetrigine) tablets are supplied as blue, film-coated, oblong tablets containing 50 mg of suzetrigine. Each tablet is debossed with the characters "VX50" on one side and plain on the other, and is packaged as follows:

Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C)

Patient counseling information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Drug interactions. Ask patients to tell you all the medications they are taking, including any herbal supplements or vitamins.

Food or drink containing grapefruit should be avoided.

When used concomitantly with hormonal contraceptives containing a progestin other than levonorgestrel or norethindrone, advise patients to use an additional nonhormonal contraceptive (such as condoms) or use alternative contraceptives during suzetrigine treatment and for 28 days after discontinuation of suzetrigine.

Females of reproductive potential. Advise females of reproductive potential that suzetrigine may reversibly impact the likelihood to become pregnant while on treatment. Patients using contraceptives should continue to use contraceptives.

Use in patients with hepatic impairment. Inquire and/or assess whether patients have hepatic impairment.

Administration instructions. Advise patients to take the starting dose of suzetrigine on an empty stomach at least 1 hour before or 2 hours after food to avoid delay in onset of action. Clear liquids may be consumed (such as water, apple juice, vegetable broth, tea, or black coffee) during this time. Avoid food or drink containing grapefruit during treatment with suzetrigine.

Subsequent doses of suzetrigine can be taken with or without food.

Patients should be instructed to swallow suzetrigine tablets whole (do not chew or crush).

Inform patients about what to do in the event they miss a dose of suzetrigine

Medication guide

See the Medication guide section of the DAILYMED drug label information.

Acknowledgement

This article was excerpted from U.S. FDA Drug Labeling information available on the DailyMed website.