Phenytoin / Dilantin

Phenytoin has one of the narrowest therapeutic windows of any oral medication — and its zero-order kinetics means a small dose change can flip a patient from subtherapeutic to toxic overnight.

Phenytoin stabilizes neuronal membranes by blocking voltage-gated sodium channels in their inactivated state, preventing the repetitive firing that drives seizures. It is indicated for tonic-clonic and focal seizures and is used as a second-line IV agent (after benzodiazepines) for status epilepticus. The therapeutic serum level is 10–20 mcg/mL. Phenytoin follows zero-order (saturation) kinetics at therapeutic doses — meaning the liver's metabolic enzymes become saturated, so even a small dose increase can produce a disproportionately large jump in serum levels. This is why toxicity can appear suddenly. Classic adverse effects include gingival hyperplasia, hirsutism, nystagmus, and ataxia. IV phenytoin must be administered no faster than 50 mg/min in adults (25 mg/min in older adults) and only in normal saline — it precipitates in dextrose solutions. Fosphenytoin, its prodrug, is preferred IV because it carries less risk of purple glove syndrome and cardiovascular collapse. Phenytoin is a potent CYP450 inducer, accelerating metabolism of warfarin, oral contraceptives, and many other drugs, reducing their effectiveness.

Key Distinctions

Don't confuse zero-order kinetics (phenytoin — small dose increase causes huge level spike) with first-order kinetics (most drugs — level rises proportionally to dose). Students mix up purple glove syndrome (local IV infiltration injury specific to phenytoin) with an allergic reaction — it's a tissue toxicity issue, not immune-mediated. Phenytoin is a CYP inducer (decreases other drug levels); valproic acid is a CYP inhibitor (increases other drug levels) — the NCLEX tests this distinction.

Clinical Pearl

Phenytoin in dextrose = crystals in the line. Always use normal saline, always use a filter, never exceed 50 mg/min. Zero-order kinetics means zero margin for error.