Journavx
(suzetrigine)Dosage & Administration
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Journavx Prescribing Information
JOURNAVX is indicated for the treatment of moderate to severe acute pain in adults.
Recommended Dosage and Administration Instructions
Swallow JOURNAVX tablets whole and do not chew or crush.
The recommended starting dose of JOURNAVX 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 [see Clinical Pharmacology (12.3)]. Clear liquids may be consumed during this time (e.g., water, apple juice, vegetable broth, tea, black coffee).
Starting 12 hours after the initial dose, take 50 mg of JOURNAVX orally every 12 hours. Take these doses with or without food [see Clinical Pharmacology (12.3)].
Avoid food or drink containing grapefruit during treatment with JOURNAVX [see Dosage and Administration (2.3)].
Use JOURNAVX for the shortest duration, consistent with individual patient treatment goals. Use of JOURNAVX 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 JOURNAVX in patients with hepatic impairment is described in Table 1.
| Degree of Hepatic Impairment (HI) | Recommended Dosage |
|---|---|
| Severe HI (Child-Pugh Class C) | Avoid use [see Use in Specific Populations (8.6)]. |
| Moderate HI (Child-Pugh Class B) | Dose 1: The recommended starting dose of JOURNAVX is 100 mg taken orally. Take the starting dose on an empty stomach at least 1 hour before or 2 hours after food [see Clinical Pharmacology (12.3)]. Clear liquids may be consumed during this time (e.g., water, apple juice, vegetable broth, tea, black coffee). Doses 2, 3, and 4: Starting 12 hours after the initial dose, take 50 mg of JOURNAVX orally every 12 hours. Take these doses with or without food [see Clinical Pharmacology (12.3)]. Dose 5 and Subsequent Doses: Starting 12 hours after Dose 4, take 50 mg of JOURNAVX orally every 24 hours. Take these dose(s) with or without food [see Clinical Pharmacology (12.3)]. |
| Mild HI (Child-Pugh Class A) | The recommended dosage is the same as in those with normal hepatic function [see Dosage and Administration (2.1)]. |
Dosage Modifications for CYP3A Inhibitors
JOURNAVX is contraindicated in patients taking strong CYP3A inhibitors. When JOURNAVX is administered to patients taking moderate CYP3A inhibitors reduce the JOURNAVX dose, as described below:
Dose 1: The recommended starting dose of JOURNAVX is 100 mg orally. Take the starting dose on an empty stomach at least 1 hour before or 2 hours after food [see Clinical Pharmacology (12.3)]. Clear liquids may be consumed during this time (e.g., water, apple juice, vegetable broth, tea, black coffee).
Doses 2, 3, and 4: Starting 12 hours after the initial dose, take 50 mg of JOURNAVX orally every 12 hours. Take these doses with or without food [see Clinical Pharmacology (12.3)].
Dose 5 and Subsequent Doses: Starting 12 hours after Dose 4, take 50 mg of JOURNAVX orally every 24 hours. Take these dose(s) with or without food [see Clinical Pharmacology (12.3)].
Avoid food or drink containing grapefruit during treatment with JOURNAVX [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Recommendations Regarding Missed Dose(s)
For patients on the standard recommended dosing schedule [see Dosage and Administration (2.1)]:
- If a dose is missed, take the missed dose as soon as possible and then take the next scheduled dose at the recommended time.
- If two or more doses are missed, take 100 mg and then take the next scheduled dose at the recommended time.
For patients with moderate hepatic impairment or patients taking moderate CYP3A inhibitors [see Dosage and Administration (2.2, 2.3)], 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.
Tablets: 50 mg, blue, film-coated, oblong tablets debossed with "VX50" on one side and plain on the other.
Pregnancy
Risk Summary
There are no available data on the use of JOURNAVX 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.
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 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 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 JOURNAVX and any potential adverse effects on the breastfed child from JOURNAVX 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 JOURNAVX treatment and for 28 days after discontinuation of JOURNAVX [see Drug Interactions (7.2)].
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 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.
JOURNAVX may reversibly impact the likelihood of females of reproductive potential to become pregnant while on treatment. Patients using contraceptives should continue to use contraceptives [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness of JOURNAVX has not been established in pediatric patients.
Geriatric Use
Of the total 1130 patients with moderate to severe acute pain who received JOURNAVX in the Phase 3 studies [see Clinical Studies (14)], 71 patients (6.3%) were 65 years of age and older.
Clinical studies of JOURNAVX 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 [see Clinical Pharmacology (12.3)].
Hepatic Impairment
JOURNAVX has not been studied in patients with severe hepatic impairment. Avoid use of JOURNAVX in patients with severe hepatic impairment (Child-Pugh Class C) [see Warnings and Precautions (5.4)]. The recommended JOURNAVX dosage is lower in patients with moderate hepatic impairment (Child-Pugh Class B) [see Dosage and Administration (2.2)] 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 [see Clinical Pharmacology (12.3)], which may increase the risk of suzetrigine adverse reactions.
Renal Impairment
JOURNAVX has not been studied in patients with renal impairment of eGFR < 15 mL/min. Avoid use of JOURNAVX in patients with renal impairment of eGFR < 15 mL/min [see Clinical Pharmacology (12.3)]. The recommended dosage in patients with eGFR > 15 mL/min is the same as those with normal kidney function.
Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1), Drug Interactions (7.1)].
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 JOURNAVX adverse reactions. Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Drug Interactions (7.1), Clinical Pharmacology (12.3)]. Reduce the JOURNAVX dosage with moderate CYP3A inhibitors [see Dosage and Administration (2.3)].
Risk of Drug Interactions with Certain CYP3A Substrates
Suzetrigine is an inducer of CYP3A. If JOURNAVX 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 JOURNAVX [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].
Risk of Drug Interactions with Certain Hormonal Contraceptives
JOURNAVX-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 JOURNAVX treatment and for 28 days after discontinuation of JOURNAVX [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].
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 JOURNAVX related adverse reactions [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Avoid use of JOURNAVX in patients with severe hepatic impairment (Child-Pugh Class C). The recommended JOURNAVX dosage is lower in patients with moderate hepatic impairment (Child-Pugh Class B) than those with normal hepatic function [see Dosage and Administration (2.2)].