Comparative Pharmacology
Head-to-head clinical analysis: PHENYTOIN versus TEGRETOL XR.
Peer-Reviewed Evidence
Head-to-head clinical analysis: PHENYTOIN versus TEGRETOL XR.
PHENYTOIN vs TEGRETOL-XR
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.
Carbamazepine stabilizes inactivated state of voltage-gated sodium channels, thereby inhibiting repetitive neuronal firing and reducing synaptic transmission.
Oral: 300-400 mg/day in 3-4 divided doses; IV: 15-20 mg/kg loading dose, then 300 mg/day maintenance.
200-400 mg orally twice daily; maximum 1200 mg/day for monotherapy, 1600 mg/day for combination therapy.
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.
Initial: 25-65 hours; chronic dosing: 12-17 hours due to autoinduction. Steady-state reached in 2-4 weeks.
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%.
Renal: ~72% as unchanged drug and metabolites (primarily glucuronides). Fecal: ~28% via bile (enterohepatic recirculation possible).
Category D/X
Category C
Anticonvulsant
Anticonvulsant