What is the recommended dosing of Topiramate (TPM) for a patient with epilepsy?

Topiramate Dosing for Epilepsy

For epilepsy, start topiramate at 25-50 mg/day and titrate by 25-50 mg weekly to a target maintenance dose of 200-400 mg/day in two divided doses for adjunctive therapy, or 400 mg/day in two divided doses for monotherapy. 1

Monotherapy Dosing

The recommended dose for topiramate monotherapy in adults and children ≥10 years is 400 mg/day in two divided doses. 1

Monotherapy Titration Schedule:

• Week 1: 25 mg twice daily (50 mg/day total) 1
• Week 2: 50 mg twice daily (100 mg/day total) 1
• Week 3: 75 mg twice daily (150 mg/day total) 1
• Week 4: 100 mg twice daily (200 mg/day total) 1
• Week 5: 150 mg twice daily (300 mg/day total) 1
• Week 6: 200 mg twice daily (400 mg/day total) 1

Clinical trials demonstrate that 75% of patients treated with 400 mg/day remained seizure-free at 1 year, compared to 59% with 50 mg/day. 2

Adjunctive Therapy Dosing

For adjunctive therapy in adults with partial seizures, the recommended total daily dose is 200-400 mg/day in two divided doses. 1

For primary generalized tonic-clonic seizures, the recommended dose is 400 mg/day in two divided doses. 1

Adjunctive Therapy Titration:

• Start at 25-50 mg/day 1
• Increase by 25-50 mg weekly 1
• Note: Titrating in increments of 25 mg/week may delay time to reach effective dose but improves tolerability 1

Doses above 400 mg/day (600,800, or 1000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. 1

Daily doses above 1,600 mg have not been studied, though this represents the maximum studied dose for epilepsy. 1

Pediatric Dosing (Ages 2-16 Years)

For children with partial seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, the recommended dose is approximately 5-9 mg/kg/day in two divided doses. 1

Pediatric Titration:

• Start at 25 mg (or less, based on 1-3 mg/kg/day) nightly for the first week 1
• Increase at 1-2 week intervals by increments of 1-3 mg/kg/day (in two divided doses) 1
• Target dose of 6 mg/kg/day reached at end of 8 weeks in primary generalized tonic-clonic seizure studies 1

Special Population Adjustments

Renal Impairment:

For patients with creatinine clearance <70 mL/min/1.73m², use one-half the usual adult dose. 1

These patients require a longer time to reach steady-state at each dose. 1

Elderly Patients:

Dosage adjustment is indicated when impaired renal function (creatinine clearance ≤70 mL/min/1.73 m²) is evident. 1

Hemodialysis:

Topiramate is cleared by hemodialysis at a rate 4-6 times greater than normal individuals. 1

A supplemental dose may be required to avoid rapid drops in plasma concentration during hemodialysis, accounting for: (1) duration of dialysis, (2) clearance rate of the dialysis system, and (3) effective renal clearance in the patient. 1

Hepatic Impairment:

Topiramate plasma concentrations may be increased in hepatically impaired patients, though the mechanism is not well understood. 1

Critical Safety Considerations

Never stop topiramate abruptly—always taper gradually to minimize seizure risk, even in patients taking it for non-epilepsy indications. 3, 4

When discontinuing, taper by taking one capsule every other day for at least 1 week before stopping completely. 4

For patients on higher doses, particularly those with seizure disorders, a more extended tapering schedule may be necessary. 4

Mandatory Counseling at Initiation:

• Women of childbearing potential must be counseled about teratogenic risk (neural tube defects, orofacial clefts) and reduced efficacy of hormonal contraceptives 5
• All patients should be warned about cognitive slowing, mental clouding, paresthesias, kidney stone risk, and metabolic acidosis 5

Common Pitfalls

The most salient adverse effect is cognitive dysfunction, especially problems with expressive speech and verbal memory, which limits use in about 25% of patients. 6

Tolerability is improved by low initial doses and slow titration to effect. 6

Do not break tablets due to bitter taste; topiramate can be taken without regard to meals. 1

No need to monitor topiramate plasma concentrations to optimize therapy. 1

Addition of topiramate to phenytoin may require phenytoin dose adjustment; addition or withdrawal of phenytoin and/or carbamazepine may require topiramate dose adjustment. 1