Use-dependent Na⁺ channel blocker — stabilises inactivated state → prevents high-frequency neuronal firing characteristic of seizure. Saturable metabolism (Michaelis-Menten) → small dose increases cause disproportionate level rises. CYP inducer + substrate.
Half-Life (t½)
PO: 19h, IV: 19h
Dosing Guidelines
PO: Typical 367 mg (Range: 300–500 mg)
IV: Typical 367 mg (Range: 300–500 mg)
Target Organ Systems
nervous
Interactions
Hormonal contraceptives (warn): CYP3A4 induction (ethinylestradiol). Crawford 1990 (PMID:2126946) verbatim: "Phenytoin reduced the AUC for EE2 from 806 +/- 50 (mean +/- s.d.) to 411 +/- 132 pg ml-1 h (P less than 0.05) and for Ng from 33.6 +/- 7.8 to 19.5 +/- 3.8 ng ml-1 h (P less than 0.05)". n=6 women on phenytoin 8-12 wk, single-dose 50 µg EE2 + 250 µg levonorgestrel. EE2 AUC 411/806 = 0.510 → induction_factor 1.96. Contraceptive failure well-documented with phenytoin.
Atorvastatin (warn): CYP3A4 induction. Bullman 2011 (PMID:21635243) verbatim: "When atorvastatin was administered with phenytoin compared with when atorvastatin was administered alone, reductions in AUC((0-τ)) and C(max) were observed for atorvastatin (54% and 24%, respectively)". 119 healthy volunteers, open-label single-sequence, atorvastatin 40 mg/d × 7d + phenytoin ~4 mg/kg/d × 28d. AUC ratio 0.46 → induction_factor 1/0.46 = 2.17. Statin efficacy loss.
Quetiapine (major): CYP3A4 induction. Wong 2001 (PMID:11199955) verbatim: phenytoin "did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients". Steady-state PK in schizophrenia / schizoaffective / bipolar patients on quetiapine + phenytoin add-on. CL × 5 → induction_factor 5.0. Dose adjustment of quetiapine likely required; loss of antipsychotic efficacy.