VIGAFYDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIGAFYDE (VIGAFYDE).
Irreversible inhibitor of GABA transaminase, increasing brain GABA levels.
| Metabolism | Minimal hepatic metabolism; primarily excreted unchanged in urine (80%) via renal filtration. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 65-70% of elimination; biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 6-8 hours in adults; in neonates, it is prolonged to 16-20 hours due to immature renal function. |
| Protein binding | Vigafattrin is not significantly protein bound; protein binding is <5% (negligible). |
| Volume of Distribution | Apparent volume of distribution is 0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 60-80%; intravenous administration yields 100%. |
| Onset of Action | Oral: 1-2 hours (peak plasma concentration); intravenous: within 30 minutes. |
| Duration of Action | Clinical effect persists for 6-12 hours after a single dose; for continuous therapy, trough levels maintain efficacy. |
Adults: 50 mg/kg/day orally divided twice daily; maximum dose 3 g/day.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-50 mL/min: 25 mg/kg/day divided twice daily. GFR 10-29 mL/min: 15 mg/kg/day once daily. GFR <10 mL/min: 10 mg/kg/day once daily. Hemodialysis: 10 mg/kg/day once daily; supplemental dose of 5 mg/kg after dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Infants (1-6 months): 50-100 mg/kg/day orally divided twice daily. Children 6 months to 16 years: 40-80 mg/kg/day orally divided twice daily; maximum 3 g/day. Infants with West syndrome: initial 50 mg/kg/day, titrate up to 100-150 mg/kg/day. |
| Geriatric use | Start at lower end of dosing range (25 mg/kg/day) and monitor renal function; adjust dose based on creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIGAFYDE (VIGAFYDE).
| Breastfeeding | Vigabatrin is excreted into human breast milk. The milk-to-plasma ratio is approximately 0.2 to 0.8. Limited data suggest that infant serum levels are low, but potential adverse effects include sedation and developmental delay. Caution is advised; consider the developmental and health benefits of breastfeeding along with the mother's clinical need for vigabatrin and any potential adverse effects on the breastfed infant. |
| Teratogenic Risk | Vigabatrin is associated with an increased risk of fetal abnormalities. In animal studies, it caused developmental toxicity at clinically relevant doses. In humans, first-trimester exposure is linked to major congenital malformations including neural tube defects, cardiac anomalies, and orofacial clefts. Second and third trimester exposure may be associated with delayed fetal growth and neurodevelopmental effects. The drug should be used during pregnancy only if the benefit outweighs the risk, and effective contraception is recommended. |
■ FDA Black Box Warning
Vigabatrin can cause permanent bilateral concentric visual field constriction, including tunnel vision. Risk increases with cumulative dose and duration. Vision loss may be severe and irreversible even after discontinuation. Because of this risk, vigabatrin is available only through a restricted distribution program (SHARE VIGABATRIN REMS).
| Serious Effects |
["Hypersensitivity to vigabatrin or any component of the formulation","Pre-existing clinically significant visual field loss"]
| Precautions | ["Visual field defects (dose- and duration-dependent, irreversible)","Suicidal ideation and behavior","Neurotoxicity (MRI abnormalities, especially in infants: intramyelinic edema)","Withdrawal seizures (abrupt discontinuation)","CNS depression (somnolence, dizziness)","Anemia","Fertility impairment (animal data)"] |
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| Fetal Monitoring | Mothers: Monitor for vision loss (peripheral visual field defects), neurological symptoms, and signs of hepatotoxicity. Periodic visual field testing and ophthalmologic exams are recommended. Fetus/neonate: Serial ultrasound for fetal growth and anatomy; consider prenatal screening for neural tube defects. Postnatally, monitor for signs of withdrawal or sedation. |
| Fertility Effects | Vigabatrin may impair male and female fertility based on animal studies. In female rats, reduced fertility and increased preimplantation loss were observed. In male rats, decreased sperm motility and viability were noted. Human data are limited, but potential effects on reproductive function should be considered. |