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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIVJOA (VIVJOA).
| Breastfeeding | It is unknown whether voclosporin is excreted in human breast milk. However, due to its molecular weight (~1245 Da) and lipophilicity, excretion into breast milk is possible. The milk-to-plasma (M/P) ratio is not known. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 12 hours after the last dose. |
| 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. |
■ FDA Black Box Warning
No FDA black box warnings.
| Serious Effects |
History of hypersensitivity to fosmanogepix or any component of the formulation.
| 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."] |
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| 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. |