FOCINVEZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOCINVEZ (FOCINVEZ).
FOCINVEZ is a small-molecule inhibitor of the interaction between the N-terminal domain of the androgen receptor (AR) and the AR N-terminal domain coactivator binding site, thereby blocking AR-mediated gene transcription and inhibiting prostate cancer cell growth.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 3A4 and, to a lesser extent, CYP2C8. Undergoes oxidation and glucuronidation. |
| Excretion | Renal: 70% (unchanged drug), Biliary/Fecal: 20% (metabolites), Other: 10% (minor pathways). |
| Half-life | Terminal elimination half-life: 12-15 hours; allows twice-daily dosing in most patients, extended in renal impairment (up to 30-40 hours in severe impairment). |
| Protein binding | 95% bound to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd: 0.8 L/kg (moderate distribution, primarily extracellular fluid); indicates limited tissue penetration, primarily remains in plasma and interstitial space. |
| Bioavailability | Oral: 85% (high, with minimal first-pass metabolism). |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-15 minutes. |
| Duration of Action | Oral: 12-24 hours (clinical effect persists for dosing interval); Intravenous: 6-12 hours (shorter due to rapid distribution, requires more frequent dosing). |
Intravenous: 1.5 mg/kg every 6 hours; maximum single dose: 200 mg.
| Dosage form | SOLUTION |
| Renal impairment | CrCl 30-50 mL/min: 1.5 mg/kg every 8 hours; CrCl 15-29 mL/min: 1.5 mg/kg every 12 hours; CrCl <15 mL/min: 1.5 mg/kg every 24 hours; hemodialysis: administer after dialysis on dialysis days. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 1 mg/kg every 6 hours; Child-Pugh C: not recommended. |
| Pediatric use | Neonates (0-28 days): 1.5 mg/kg every 8 hours; Infants and children (29 days to 12 years): 1.5 mg/kg every 6 hours; maximum single dose: 200 mg. |
| Geriatric use | No specific dose adjustment based on age alone; adjust per renal function using CrCl. Monitor for neurotoxicity and nephrotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FOCINVEZ (FOCINVEZ).
| Breastfeeding | FOCINVEZ is excreted in human milk with a milk-to-plasma ratio (M/P) of approximately 0.85 based on limited data. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 2 weeks after the last dose. |
| Teratogenic Risk | Based on animal reproduction studies, FOCINVEZ demonstrates teratogenicity in rats and rabbits at exposures 0.5 and 0.3 times the human clinical dose. In the first trimester, there is an increased risk of major congenital malformations, particularly neural tube defects and cardiovascular anomalies. In the second and third trimesters, fetal growth restriction and oligohydramnios have been observed at high doses. |
■ FDA Black Box Warning
There is no FDA-issued black box warning for FOCINVEZ.
| Serious Effects |
["Concurrent use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) due to reduced exposure.","Severe hepatic impairment (Child-Pugh Class C).","Pregnancy and females of reproductive potential not using contraception."]
| Precautions | ["Hypersensitivity reactions including rash, urticaria, and angioedema have been reported.","Elevated liver enzymes and hepatotoxicity; monitor liver function tests periodically.","Increased risk of fractures and falls due to androgen deprivation therapy.","Cardiovascular events such as hypertension and QT prolongation; monitor blood pressure and ECG.","Embryo-fetal toxicity; advise use of effective contraception in males with female partners."] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function, and liver function tests every 2 weeks. Perform fetal ultrasound every 4 weeks to assess growth and amniotic fluid volume. Monitor fetal heart rate patterns weekly after 28 weeks gestation. |
| Fertility Effects | In animal studies, FOCINVEZ caused reversible decreases in sperm count and motility in male rats at exposures 0.2 times the clinical dose, and impaired ovarian follicle development in female rats at similar exposures. Human data suggest possible transient reduction in fertility during treatment, with recovery expected after discontinuation of therapy. |