Suzetrigine (Monograph)

Brand name: Journavx
Drug class: Analgesics and Antipyretics, Miscellaneous

Introduction

Suzetrigine is a sodium channel blocker.

Uses for Suzetrigine

Suzetrigine has the following uses:

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

Suzetrigine Dosage and Administration

General

Suzetrigine is available in the following dosage form(s) and strength(s):

Tablets: 50 mg

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Swallow suzetrigine tablets whole and do not chew or crush.
Recommended starting dose 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 (e.g., water, apple juice, vegetable broth, tea, black coffee).
Starting 12 hours after the starting dose, take 50 mg of suzetrigine orally every 12 hours. Take these doses with or without food.
Use suzetrigine for the shortest duration, consistent with individual patient treatment goals. Use of suzetrigine for the treatment of acute pain has not been studied beyond 14 days.
See the full prescribing information for recommended dosage in patients with hepatic impairment and patients receiving concomitant use of CYP3A inhibitors, and recommendations regarding missed dose(s).
Avoid food or drink containing grapefruit during treatment with suzetrigine.

Cautions for Suzetrigine

Contraindications

Concomitant use with strong CYP3A inhibitors is contraindicated.

Warnings/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 (e.g., 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 the drug.

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 those with normal hepatic function.

Specific Populations

Pregnancy

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 defect, 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.

Lactation

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

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 the drug.

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 prior to 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 them.

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 65 years of age and older to determine whether they respond differently from younger patients. However, based on population pharmacokinetic analyses in patients ranging in age 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 those with normal hepatic function. The recommended dosage in patients with mild hepatic impairment (Child-Pugh Class A) is the same as 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 those with normal kidney function.

Common Adverse Effects

The most common adverse reactions (greater incidence in suzetrigine-treated patients compared to placebo-treated patients) were pruritus, muscle spasms, increased creatine phosphokinase, and rash.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Strong and Moderate CYP3A inhibitors: Concomitant use with strong CYP3A inhibitors is contraindicated. Reduce the suzetrigine dose when used concomitantly with moderate CYP3A inhibitors. Avoid food or drink containing grapefruit.
Strong and moderate CYP3A inducers: Avoid suzetrigine use with strong or moderate CYP3A inducers.
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.
Hormonal contraceptives: suzetrigine-treated patients using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use an additional nonhormonal contraceptive method or an alternative hormonal contraceptive during concomitant use and for 28 days after suzetrigine discontinuation.

Actions

Mechanism of Action

Suzetrigine is a selective blocker of the Na_V1.8 voltage-gated sodium channel, compared to other known voltage-gated sodium channels (Na_V1.1 through 1.9). Na_V1.8 is expressed in peripheral sensory neurons including dorsal root ganglion neurons, where its role is to transmit pain signals (action potentials). By selectively inhibiting Na_V1.8 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 Na_V1.8 than suzetrigine by 3.7-fold.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients to inform their clinicians of all the medications they are taking, including any herbal supplements or vitamins.
Advise patients that food or drinks 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.
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 them.
Inquire and/or assess whether patients have hepatic impairment.
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. 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.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.