Phenytoin

Actions

• Blocks voltage-dependent Na+ channels.

Metabolism

Hepatic

Enzymes involved

• CYP2C9
• CYP2C19

Elimination

Renal and fecal

Enzyme induction

• CYP2B6
• CYP2C8
• CYP2C9
• CYP2C19
• CYP3A4

Therapeutic serum concentration range

5-25 μg/ml

Half-life

12-60 hours

Plasma protein binding

90%

Important side-effects

Suicidal behavior and ideation.

Serious and sometimes fatal dermatologic reactions, including Stevens-Johnson syndrome and TEN.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Hepatic injury.

Blood dyscrasias.

Exacerbation of Porphyria.

Indications

Generalized tonic-clonic seizures.

Focal seizures with or without generalization.

Not effective against absence seizures.

May aggravate myoclonic and absence seizures.

Dosing recommendation

Start with 100 mg/day.

Increase to target dose over 3–7 days.

Target dose: 200–400 mg/day divided in 1-2 doses.

Renal impairment

Careful titration and monitoring of serum concentration is advised in patients with impaired renal function.

Hepatic impairment

Careful titration and monitoring of serum concentration is advised in patients with impaired hepatic function.

Serum concentration changes during pregnancy

Total level decreases by 60-70%. Free fraction level decreases by 16-40%.