Comparative Pharmacology
Head-to-head clinical analysis: PHENYTOIN versus TEGRETOL.
Peer-Reviewed Evidence
Head-to-head clinical analysis: PHENYTOIN versus TEGRETOL.
PHENYTOIN vs TEGRETOL
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Phenytoin is a hydantoin anticonvulsant that stabilizes neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. It use-dependently blocks voltage-gated sodium channels, prolonging their inactivation phase and reducing high-frequency repetitive firing of action potentials.
Voltage-gated sodium channel blocker; stabilizes neuronal membranes and inhibits repetitive firing. Also inhibits glutamate release and enhances GABA activity.
Oral: 300-400 mg/day in 3-4 divided doses; IV: 15-20 mg/kg loading dose, then 300 mg/day maintenance.
Initial: 200 mg orally twice daily; increase by 200 mg/day at weekly intervals. Maintenance: 800-1200 mg/day in 2-4 divided doses. Maximum dose: 1600 mg/day. Extended-release: 200-400 mg twice daily.
None Documented
None Documented
Clinical Note
moderatePhenytoin + Digoxin
"The metabolism of Digoxin can be increased when combined with Phenytoin."
Clinical Note
moderateFosphenytoin + Digoxin
"The metabolism of Digoxin can be increased when combined with Fosphenytoin."
Clinical Note
moderatePhenytoin + Digitoxin
"The metabolism of Digitoxin can be increased when combined with Phenytoin."
Clinical Note
moderateFosphenytoin + Digitoxin
"The metabolism of Digitoxin can be increased when combined with Fosphenytoin."
Average terminal half-life 22 hours (range 7–42 hours) in adults; dose-dependent due to saturation of metabolism at therapeutic concentrations (10–20 mg/L). Half-life increases with higher doses.
Single dose: 25–65 hours (mean ~35 h); chronic therapy: 12–17 hours due to autoinduction; clinical context: requires 3–4 weeks to reach steady-state after dose adjustment.
Primarily hepatic metabolism (>95%); less than 5% excreted unchanged in urine. Renal excretion of metabolites (glucuronides) accounts for ~80% of elimination; biliary/fecal excretion of metabolites ~20%.
Primarily hepatic metabolism; ~72% excreted in urine (as metabolites, <2% unchanged), ~28% excreted in feces via bile.
Category D/X
Category C
Anticonvulsant
Anticonvulsant