Topiramate

Actions

• Blocks voltage-dependent Na+ channels at high firing frequencies.
• Binds to GABA receptor (at different site than benzodiazepines) and increases frequency at which GABA opens chloride channels.
• Antagonizes glutamate at AMPA/kainate receptors.
• Inhibits carbonic anhydrase.

Metabolism

Hepatic

Enzymes involved

• CYP3A4
• CYP2C19

Elimination

Renal >70%

Enzyme induction

• CYP3A4

Enzyme inhibition

• CYP2C19

Therapeutic serum concentration range

2-25 μg/ml

Half-life

20-30 hours

Plasma protein binding

15%

Important side-effects

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate.

Oligohidrosis and hyperthermia.

Metabolic acidosis.

Suicidal behavior and ideation.

Cognitive-related dysfunction and psychiatric/behavioral disturbances.

Kidney stones.

Indications

Focal seizures with or without generalization.

Generalized tonic-clonic seizures.

Dosing recommendation

Start with 25 mg/day.

Increase by 25-50 mg/day in increments every 2 weeks.

Target dose: 100–400 mg/day divided in 2 doses.

Renal impairment

Reduction by 50% of the initial and target dose is recommended in patients with impaired renal function and creatinine clearance ≤ 70 ml/min.

Hepatic impairment

Cautious titration and serum concentration monitoring is advised in patients with moderately to severely impaired liver function (Child-Pugh Class B and C) as clearance of topiramate is reduced.

Serum concentration changes during pregnancy

Total level decreases by 30-35%. Free fraction level decreases by 30-35%.