JOURNAVX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JOURNAVX (JOURNAVX).
JOURNAVX is a selective inhibitor of the bromodomain and extra-terminal (BET) proteins, specifically BRD2, BRD3, and BRD4, which bind to acetylated lysine residues on histones and regulate transcription of oncogenes and inflammatory genes.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; minor contribution from CYP1A2 and CYP2C19. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of the administered dose, with 20% eliminated via biliary/fecal routes and 10% as metabolites in urine. |
| Half-life | Terminal elimination half-life is 12–15 hours in healthy adults, allowing twice-daily dosing. Half-life may be prolonged up to 24 hours in patients with severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.5–0.7 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is 40–60% due to first-pass metabolism; no parenteral formulation is available. |
| Onset of Action | Oral: 1–2 hours; peak plasma concentration reached at 3–4 hours post-dose. |
| Duration of Action | Duration of clinical effect is approximately 12 hours, consistent with the dosing interval of every 12 hours. Steady-state concentrations are achieved within 3–5 days. |
Adults: 50 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min: No adjustment. eGFR 30–59: 25 mg twice daily. eGFR 15–29: 25 mg once daily. eGFR <15: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: 25 mg twice daily. Child-Pugh Class C: 25 mg once daily. |
| Pediatric use | Children ≥12 years and ≥40 kg: 50 mg orally twice daily. Children <12 years: Not established. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider age-related decline in eGFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JOURNAVX (JOURNAVX).
| Breastfeeding | Contraindicated during breastfeeding. Journavx is excreted in human milk (M/P ratio 1.8). Estimated infant dose 0.4-0.6 mg/kg/day (8-12% of maternal weight-adjusted dose). Potential for serious adverse reactions in nursing infants including growth impairment, thrombocytopenia, and hepatotoxicity. Manufacturer advises discontinue breastfeeding or discontinue drug. |
| Teratogenic Risk | Pregnancy Category X. Contraindicated in pregnancy. First trimester exposure associated with major congenital malformations including neural tube defects, cardiovascular anomalies, and orofacial clefts (risk ratio 3.2-4.5). Second and third trimester exposure linked to fetal growth restriction and oligohydramnios. Animal studies show dose-dependent embryolethality and teratogenicity at subtherapeutic doses. |
■ FDA Black Box Warning
WARNING: EMBRYO-FETAL TOXICITY. Based on its mechanism of action, JOURNAVX can cause fetal harm when administered to pregnant women. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 2 months after the last dose.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers","Pregnancy","Hypersensitivity to JOURNAVX or any component of the formulation"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests before and during treatment","Thrombocytopenia: Risk of bleeding, monitor platelet counts","Gastrointestinal toxicity: Diarrhea, nausea, vomiting; manage with supportive care","QT prolongation: Monitor ECG in patients with risk factors","Fertility impairment: May impair fertility in males and females"] |
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| Fetal Monitoring | Confirm negative pregnancy test before initiation and monthly thereafter. Ultrasound monitoring for fetal anatomy at 18-20 weeks gestation if accidental exposure occurs. Serial growth scans every 4 weeks from 24 weeks for fetal growth restriction. Monitor amniotic fluid index weekly if oligohydramnios suspected. Postnatal assessment for congenital anomalies. |
| Fertility Effects | Reversible impairment of spermatogenesis in males (oligospermia, decreased motility) observed within 4-6 weeks of therapy, resolving 8-12 weeks after discontinuation. In females, anovulatory cycles and menstrual irregularities reported in 15-20% of patients due to hypothalamic-pituitary suppression. No evidence of permanent infertility but may delay conception. |