Journavx (suzetrigine)

No dosing information is available for this tab.

Suzetrigine is administered orally as tablets. Swallow the tablets whole; do not chew or crush.

Administer the starting dose on an empty stomach at least 1 hour before or 2 hours after food. Clear liquids (e.g., water, apple juice, vegetable broth, tea, black coffee) may be consumed at this time. Administer subsequent doses with or without food.

Avoid food or drink containing grapefruit during treatment.

If a dose is missed, take the missed dose as soon as possible and then resume the regular dosing schedule.

If 2 or more doses are missed, take 100 mg and then take the next scheduled dose at the recommended time.

If a dose is missed in patients taking concomitant moderate cytochrome P-450 (CYP)3A inhibitors or in those with moderate hepatic impairment, take the missed dose as soon as possible. If the next scheduled dose is within 6 hours, skip the next scheduled dose, and resume the regular dosing schedule.

Store at 20-25degreesC; excursions permitted to 15-30degreesC.

No dosing information is available for this tab.

Suzetrigine inhibits cytochrome P-450 (CYP) 2C8, CYP2C9, and CYP2C19, but is not expected to result in clinically important drug interactions. Suzetrigine does not inhibit CYP1A2, CYP2B6, CYP2D6, and CYP3A. Suzetrigine induces CYP3A and to a lesser extent CYP2B6, CYP2C8, CYP2C9, and CYP2C19. Suzetrigine does not induce CYP1A2. Suzetrigine does not inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1. Suzetrigine inhibits organic anion transporter polypeptide (OATP)1B1, OATP1B3, and organic anion transporter (OAT) 3 but is not expected to result in clinically important drug interactions. Suzetrigine does not inhibit breast cancer resistance protein (BCRP), OAT1, organic cation transporter (OCT)2, multidrug and toxin extrusion protein (MATE)1, and MATE2/K transporters.

M6-SUZ does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A enzymes. M6-SUZ inhibits OATP1B1, OATP1B3, OAT1, and OAT3 but is not expected to result in clinically important drug interactions. M6-SUZ does not inhibit P-glycoprotein (P-gp), BCRP, OCT2, MATE1, and MATE2/K transporters.

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.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Suzetrigine/Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of suzetrigine.(1)

CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of suzetrigine.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The US manufacturer of suzetrigine states that concurrent use of moderate CYP3A4 inducers should be avoided.(1)

DISCUSSION: Concomitant administration of efavirenz (moderate CYP3A inducer) with suzetrigine is predicted to decrease suzetrigine and active metabolite M6-SUZ area-under-curve (AUC) by 63% and 60%, respectively, while suzetrigine maximum concentration (Cmax) is predicted to decrease by 29% and M6-SUZ Cmax is predicted to increase by 1.3-fold, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3)

Suzetrigine/Strong Cyp3a4 Inducers

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strong inducers of CYP3A4 may induce the metabolism of suzetrigine.(1)

CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 inducers may reduce the clinical effectiveness of suzetrigine.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The US manufacturer of suzetrigine states that concurrent use of strong CYP3A4 inducers should be avoided.(1)

DISCUSSION: In a study, concomitant use of rifampin (strong CYP3A4 inducer) decreased suzetrigine maximum concentration (Cmax) by 80% and area-under-curve (AUC) by 93%. Active metabolite M6-SUZ AUC decreased by 85% and Cmax was increased by 1.3-fold.(1) Strong CYP3A4 inducers linked to this monograph are: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's Wort.(2,3)

Suzetrigine/Strong Cyp3a4 Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Suzetrigine and M6-SUZ (active metabolite of suzetrigine) are CYP3A4 substrates. Strong CYP3A4 inhibitors increase suzetrigine and M6-SUZ exposures, which may cause suzetrigine adverse reactions.(1)

CLINICAL EFFECTS: The concurrent administration of a strong CYP3A4 inhibitor may result in elevated levels of and toxicity from suzetrigine including pruritis, muscle spasms, increased blood creatine phosphokinase, and rash.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of suzetrigine and strong CYP3A4 inhibitors is contraindicated.(1)

DISCUSSION: Concomitant administration of itraconazole (a strong CYP3A4 inhibitor) with a single dose of suzetrigine increased the area-under-curve (AUC) of suzetrigine and active metabolite M6-SUZ by 4.8-fold and 4.4-fold, respectively, while the maximum concentration (Cmax) of suzetrigine increased by 1.5-fold and Cmax of M6-SUZ decreased by 32%.(1) Strong CYP3A4 inhibitors include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, ensitrelvir, grapefruit, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir/ritonavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, relacorilant, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(2-3)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Moderate Cyp3a4 Inducers/Zanubrutinib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Zanubrutinib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of zanubrutinib.(1)

CLINICAL EFFECTS: The concurrent administration of moderate CYP3A4 inducers may result in decreased levels and effectiveness of zanubrutinib.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of zanubrutinib states that concurrent use with moderate CYP3A4 inducers should be avoided. If concurrent use cannot be avoided, increase zanubrutinib dosage to 320 mg twice daily.(1)

DISCUSSION: Co-administration of multiple doses of efavirenz, a moderate CYP3A4 inducer, is predicted to decrease zanubrutinib Cmax by 58% and AUC by 60%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, suzetrigine, telotristat ethyl, thioridazine, and tovorafenib.(2-3)

Suzetrigine/Selected Hormonal Contraceptives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Suzetrigine may induce the metabolism of hormonal contraceptives containing progestins other than levonorgestrel and norethindrone.(1)

CLINICAL EFFECTS: Concurrent use of suzetrigine and hormonal contraceptives containing progestins other than levonorgestrel or norethindrone may result in decreased levels and effectiveness of the contraceptive.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of suzetrigine advises that suzetrigine-treated patients using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should either: - Use additional non-hormonal contraceptives, - Use alternative contraceptives such as a combined oral contraceptive containing ethinyl estradiol as the estrogen and levonorgestrel or norethindrone as the progestin, or - Use an intrauterine system The alternative birth control method should be used during treatment with suzetrigine and for 28 days after discontinuation of suzetrigine.(1)

DISCUSSION: 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.(1) Suzetrigine administered 50 mg every 12 hours at steady state decreased the area-under-curve (AUC) of midazolam (a CYP3A4 substrate) by 48% and maximum concentration (Cmax) by 37%.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Moderate And Weak Cyp3a4 Inducers/Tacrolimus

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may accelerate the metabolism of tacrolimus.(1)

CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of tacrolimus.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of tacrolimus recommends monitoring tacrolimus whole blood trough concentrations and adjusting tacrolimus dose if needed. Monitor clinical response closely.(1)

DISCUSSION: A 13-year-old cystic fibrosis patient with a history of liver transplant on stable doses of tacrolimus underwent 2 separate courses of nafcillin therapy (a moderate CYP3A4 inducer). During the 1st course of nafcillin, his tacrolimus levels started to fall 3 days after starting nafcillin, became undetectable at day 8, and recovered to therapeutic levels without a change in tacrolimus dose 5 days after discontinuation of nafcillin. During the 2nd course of nafcillin, tacrolimus level became undetectable 4 days after starting nafcillin and recovered 3 days after stopping nafcillin.(2) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, modafinil, nafcillin, repotrectinib, telotristat, and tovorafenib.(3,4) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, nevirapine, oritavancin, omaveloxolone, oxcarbazepine, pioglitazone, relugolix, rufinamide, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vinblastine, and zanubrutinib.(3,4)

Moderate And Weak Cyp3a4 Inducers/Ubrogepant

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may induce the metabolism of ubrogepant.(1)

CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of ubrogepant.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with moderate or weak CYP3A4 inducers. Initial dose of ubrogepant should be 100 mg. If a second dose is needed, the dose of ubrogepant should be 100 mg.(1)

DISCUSSION: Coadministration of ubrogepant with rifampin, a strong CYP3A4 inducer, resulted in an 80% reduction in ubrogepant exposure. No dedicated drug interaction studies were conducted to assess concomitant use with moderate or weak CYP3A4 inducers. Dose adjustment for concomitant use of ubrogepant with moderate or weak CYP3A4 inducers is recommended based on a conservative prediction of 50% reduction in exposure of ubrogepant.(1) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, rifabutin, telotristat, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, dexamethasone, dicloxacillin, echinacea, elafibranor, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, relugolix, repotrectinib, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)

Selected Moderate-Weak Cyp3a4 Inducers/Exemestane

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: CYP3A4 inducers may induce the metabolism of exemestane.(1)

CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in decreased levels and effectiveness of exemestane.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The US manufacturer of exemestane recommends that patients receiving concurrent therapy with a strong CYP3A4 inducer receive 50 mg of exemestane daily after a meal.(1) It may be prudent to consider a dosage increase for patients receiving weaker CYP3A4 inducers.

DISCUSSION: In a study in 10 healthy postmenopausal subjects, pretreatment with rifampin (a strong CYP3A4 inducer, 600 mg daily for 14 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of exemestane (25 mg) by 54% and 41%, respectively.(1) Strong inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 80% or more and include: carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.(1-3) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, gingko, ginseng, glycyrrhizin, lorlatinib, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)

Suzetrigine/Moderate Cyp3a4 Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Suzetrigine and M6-SUZ (active metabolite of suzetrigine) are CYP3A4 substrates. Moderate CYP3A4 inhibitors increase suzetrigine and M6-SUZ exposures, which may cause suzetrigine adverse reactions.(1)

CLINICAL EFFECTS: The concurrent administration of a moderate CYP3A4 inhibitor may result in elevated levels of and toxicity from suzetrigine including pruritis, muscle spasms, increased blood creatine phosphokinase, and rash.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid the use of moderate CYP3A4 inhibitors with suzetrigine. The US manufacturer of suzetrigine states when suzetrigine is administered to patients taking moderate CYP3A4 inhibitors reduce the suzetrigine dose as follows: -Dose 1: The recommended starting dose of suzetrigine is 100 mg orally. -Dose 2, 3, and 4: Starting 12 hours after the initial dose, take 50 mg of suzetrigine orally every 12 hours. -Dose 5 and Subsequent Doses: Starting 12 hours after Dose 4, take 50 mg of suzetrigine orally every 24 hours.(1)

DISCUSSION: In a PKPB model, concomitant administration of fluconazole (a moderate CYP3A4 inhibitor) with suzetrigine with the recommended dosage modification is predicted to increase the area-under-curve (AUC) of suzetrigine and active metabolite M6-SUZ by 1.5-fold and 1.2-fold, respectively, while the maximum concentration (Cmax) of suzetrigine and M6-SUZ by 1.4-fold and 1.1-fold, respectively, when compared to the regular recommended dosage in the absence of fluconazole.(1) Moderate CYP3A4 inhibitors linked to this monograph include: amprenavir, aprepitant, atazanavir, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, darunavir, diltiazem, dronedarone, duvelisib, erythromycin, fedratinib, fluconazole, fluvoxamine, fosamprenavir, fosnetupitant, imatinib, isavuconazole, oral lefamulin, lenacapavir, letermovir, netupitant, nilotinib, nirogacestat, rilzabrutinib, schisandra, stiripentol, tofisopam, treosulfan, verapamil, and voxelotor.(2-3)

*Concomitant use of suzetrigine with strong cytochrome P-450 (CYP)3A inhibitors.

There are no contraindication contraindications for this drug.

• Child-pugh class B hepatic impairment
• Disease of liver

There are no moderate contraindications for this drug.

The most common adverse reactions of suzetrigine in clinical studies were pruritus, muscle spasms, increased creatine phosphokinase, and rash.

There are no severe adverse reactions for this drug.

More Frequent

• Increased creatine kinase level
• Muscle spasm
• Pruritus of skin
• Skin rash

Rare or Very Rare

• Cardiac arrhythmia
• Drowsy
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Syncope

No enhanced messaging available.

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

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.

It is unknown whether suzetrigine or its metabolites are present in human milk or whether the drug has any effects on the breastfed infant or 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. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for suzetrigine and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

There were limited numbers of patients >=65 years of age in clinical studies of suzetrigine to determine if they respond differently from younger patients. Age does not have an impact on suzetrigine exposure based on population pharmacokinetic analyses in patients ranging in age from 18 to 75 years.