Topiramate

• Epilepsy
• Migraine Prevention
• Seizure Disorders
• Weight Management (with phentermine)

Topiramate is an anticonvulsant medication with multiple mechanisms of action. It is used to treat epilepsy, prevent migraine headaches, and (in combination with phentermine) for weight management.

Mechanism of Action

Topiramate works through multiple mechanisms:

• Sodium channel blockade: Stabilizes neuronal membranes by blocking voltage-gated sodium channels
• GABA-A receptor potentiation: Enhances GABA-mediated inhibition
• Glutamate receptor antagonism: Blocks AMPA/kainate glutamate receptors
• Carbonic anhydrase inhibition: Weak inhibition of CA isoenzymes II and IV
• Reduces neuronal excitability: Net effect of antiexcitatory and proinhibitory actions

Available Formulations

• Immediate-release tablets: 25 mg, 50 mg, 100 mg, 200 mg
• Sprinkle capsules: 15 mg, 25 mg
• Extended-release capsules (Trokendi XR, Qudexy XR): Various strengths

Medical Uses

FDA-Approved Indications:

• Partial-onset seizures and primary generalized tonic-clonic seizures (adults and children ≥2 years)
• Lennox-Gastaut syndrome (adjunctive therapy)
• Migraine prophylaxis (adults and adolescents ≥12 years)

In Combination (Qsymia):

• Chronic weight management (with phentermine)

Dosing Guidelines

Epilepsy (Monotherapy):

• Week 1: 25 mg twice daily
• Titrate by 25-50 mg/week
• Target: 200 mg twice daily (adults)

Epilepsy (Adjunctive):

• Start 25-50 mg/day; titrate to 200-400 mg/day divided twice daily

Migraine Prophylaxis:

• Week 1: 25 mg nightly
• Increase by 25 mg weekly
• Target: 50 mg twice daily (100 mg/day)

Important Safety Information

Boxed Warning:

• Fetal toxicity: Increased risk of oral clefts (cleft lip/palate) with first trimester exposure

Contraindications:

• Recent alcohol use (within 6 hours before and after extended-release)
• With metformin for weight loss in patients with metabolic acidosis

Warnings and Precautions:

• Metabolic acidosis: Monitor bicarbonate levels, especially in renal disease, severe respiratory disorders, or with ketogenic diet
• Cognitive dysfunction: Word-finding difficulty, memory impairment, concentration problems
• Kidney stones: Increased risk; maintain adequate hydration
• Oligohidrosis and hyperthermia: Especially in children; monitor during hot weather
• Acute myopia and secondary angle-closure glaucoma: Usually within first month; discontinue if occurs
• Mood disorders: Monitor for depression and suicidal ideation

Drug Interactions

• CNS depressants: Additive CNS depression
• Carbonic anhydrase inhibitors (acetazolamide, zonisamide): Increased kidney stone risk
• Oral contraceptives: Reduced efficacy at doses ≥200 mg/day
• Valproic acid: Increased ammonia; monitor for hyperammonemia/encephalopathy
• Lithium: May increase or decrease lithium levels
• Phenytoin, carbamazepine: May reduce topiramate levels

Special Populations

• Hepatic Impairment: Use with caution
• Renal Impairment: Reduce dose by 50% if CrCl <70 mL/min
• Pregnancy: Avoid if possible; contraindicated for migraine prevention
• Lactation: Present in breast milk; monitor infant
• Pediatric: Approved for seizures ≥2 years; migraine ≥12 years