VIVJOA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIVJOA (VIVJOA).
VIVJOA (fosmanogepix) is a first-in-class antifungal agent that inhibits the fungal enzyme Gwt1, which is involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis. This disrupts cell wall integrity and fungal growth.
| Metabolism | Primarily metabolized by hydrolysis to manogepix, the active moiety, and further metabolized via glucuronidation and oxidation by CYP3A4 and CYP3A5. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with <1% excreted unchanged in urine; fecal elimination accounts for approximately 88% of the administered dose as metabolites. |
| Half-life | Terminal elimination half-life is approximately 20–26 hours, supporting once-daily dosing for sustained therapeutic levels. |
| Protein binding | Approximately 88–90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is approximately 1.4 L/kg, indicating extensive extravascular distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 30% due to first-pass metabolism; absorption is enhanced when taken with a high-fat meal (increase by 2–3 fold). |
| Onset of Action | Oral administration: clinical effect on testosterone suppression observed within 2–4 weeks; maximal effect typically by 8–12 weeks. |
| Duration of Action | Duration of testosterone suppression persists for the dosing interval (24 hours) with once-daily oral dosing; continuous therapy required to maintain effect. |
| Molecular Weight | 313.35 |
VIVJOA (750 mg tablet) is administered as a single oral dose of 750 mg, taken once daily for 6 weeks.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients below 18 years of age. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. Use with caution due to potential age-related renal or hepatic impairment. |
| 1st trimester | VIVJOA is contraindicated in pregnancy. It is an inhibitor of Janus kinases (JAKs) and has been shown to cause embryo-fetal harm in animal studies. Use effective contraception during treatment and for at least one week after the last dose. |
| 2nd trimester | VIVJOA is contraindicated in the second trimester due to risks of teratogenicity and adverse fetal outcomes. Avoid use. |
| 3rd trimester | VIVJOA is contraindicated in the third trimester. Potential risks include fetal harm and neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for VIVJOA (VIVJOA).
| Placental transfer | VIVJOA crosses the placenta in animal models. In humans, based on its molecular weight and pharmacology, placental transfer is expected. Available data from animal studies indicate transfer to fetal tissues. |
| Breastfeeding | It is unknown whether VIVJOA is excreted in human milk. Given the potential for serious adverse reactions in nursing infants, women should not breastfeed during treatment and for at least one week after the last dose. |
■ FDA Black Box Warning
No FDA black box warnings.
| Serious Effects |
PregnancyHypersensitivity to the active substance or any excipientsSevere hepatic impairment (Child-Pugh C)AST or ALT >5 times ULN (unless due to underlying disease)Active serious infection including tuberculosis (TB) requiring antimicrobial therapyAbsolute neutrophil count <1000 cells/mm3Platelet count <50,000/mm3 (unless due to underlying disease)Hemoglobin <8 g/dL (unless due to underlying disease)
| Precautions | Hepatotoxicity: Elevations of liver enzymes have been reported; monitor liver function tests., Infusion-related reactions: May include hypotension, dyspnea, and flushing; slow infusion rate if reactions occur., Drug interactions: Avoid coadministration with strong CYP3A4 inducers; use caution with moderate CYP3A4 inducers and strong CYP3A4 inhibitors. |
| Food/Dietary | No specific food interactions reported. VIVJOA can be taken with or without food. |
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| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | VIVJOA (voclosporin) is classified as FDA Pregnancy Category C. Animal studies have shown embryofetal toxicity (including increased postimplantation loss, reduced fetal weights, and skeletal variations) at maternal exposures similar to the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Teratogenic risk is greatest during the first trimester; however, data in humans are insufficient to quantify risk by trimester. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, eGFR), and trough voclosporin concentrations regularly. In pregnant patients, perform fetal ultrasound to assess growth and anatomy. Monitor for signs of maternal hypertension and proteinuria, which may worsen. Consider therapeutic drug monitoring to maintain trough concentrations within the target range (20-50 ng/mL) due to pregnancy-induced pharmacokinetic changes. |
| Fertility Effects | Reproductive studies in animals have shown no impairment of fertility in males or females at exposures up to 2.5 times the human therapeutic exposure. However, data on human fertility are limited. Based on its mechanism (calcineurin inhibition), potential effects on gonadal function cannot be excluded. Patients should be counseled about the uncertainty regarding fertility outcomes. |
| Clinical Pearls | VIVJOA (ponesimod) is a sphingosine 1-phosphate receptor modulator for relapsing forms of multiple sclerosis. Monitor for bradyarrhythmia at treatment initiation; obtain ECG before first dose and observe for 6 hours. Avoid use in patients with recent myocardial infarction, stroke, or certain arrhythmias. Check liver function tests and ophthalmic exams (macular edema risk). Live vaccines are contraindicated during and for 4 weeks after treatment. |
| Patient Advice | Take VIVJOA exactly as prescribed, with or without food. · You may experience a slow heart rate after the first dose; you will be monitored for at least 6 hours. · Report any vision changes, such as blurred vision or blind spots, immediately. · Women of childbearing age must use effective contraception during and for 7 days after stopping treatment. · Avoid live vaccines while taking VIVJOA and for 4 weeks after your last dose. · Contact your doctor if you develop signs of infection, such as fever or cough. |