Topiramate Dosing
Topiramate dosing varies significantly by indication: for epilepsy monotherapy, target 400 mg/day in divided doses; for epilepsy adjunctive therapy, use 200-400 mg/day; for migraine prevention, use 100 mg/day; for obesity management as phentermine-topiramate ER (Qsymia), titrate from 3.75/23 mg to a maximum of 15/92 mg daily; and for neuropathic pain, consider 400 mg/day, though evidence is limited. 1, 2, 3, 2
Epilepsy Dosing
Monotherapy
- Target dose: 400 mg/day in two divided doses for adults and children ≥10 years 1
- Titration schedule over 6 weeks: 1
- Week 1: 25 mg twice daily
- Week 2: 50 mg twice daily
- Week 3: 75 mg twice daily
- Week 4: 100 mg twice daily
- Week 5: 150 mg twice daily
- Week 6: 200 mg twice daily (target)
- In clinical trials, only 58% of patients achieved the full 400 mg/day dose, with mean achieved dose of 275 mg/day 1
Adjunctive Therapy
- Adults: 200-400 mg/day in two divided doses for partial seizures; 400 mg/day for primary generalized tonic-clonic seizures 1
- Start at 25-50 mg/day, increase by 25-50 mg/week 1
- Pediatric patients (ages 2-16): 5-9 mg/kg/day in two divided doses 1
- Begin at 25 mg (or 1-3 mg/kg/day) nightly for first week, then increase by 1-3 mg/kg/day at 1-2 week intervals 1
- Doses above 1,600 mg/day have not been studied and are not recommended 1
Migraine Prevention
- Target dose: 100 mg/day provides optimal efficacy 3
- Titrate by 25 mg/week for 8 weeks 3
- Lower doses (50 mg/day) show some efficacy with better tolerability 4, 3
- Approximately 25% of patients respond to 50 mg/day, while 51% require 100 mg/day in clinical practice 4
- Significant reduction in migraine frequency occurs within the first month of treatment at 100-200 mg/day 3
- The 200 mg/day dose does not provide substantially greater benefit than 100 mg/day but increases adverse effects 3
Obesity Management (Phentermine-Topiramate ER/Qsymia)
- Mandatory titration schedule: 5, 2
- Days 1-14: 3.75 mg/23 mg daily (morning)
- Day 15 onward: 7.5 mg/46 mg daily
- Evaluate at 12 weeks: if <3% weight loss, increase to 11.25 mg/69 mg daily for 14 days, then 15 mg/92 mg daily
- Discontinue if <5% weight loss after 12 weeks at maximum dose (15/92 mg) 2
- Take once daily in the morning; do not split doses 5
- Maximum dose: 15 mg phentermine/92 mg topiramate daily 2, 5
Neuropathic Pain
- Suggested dose: 400 mg/day, though evidence is limited 6
- Doses studied range from 25-800 mg/day 6
- Listed as an option at 25-100 mg/day for painful diabetic peripheral neuropathy, but not a first-line agent 2
- First-line agents for neuropathic pain include duloxetine, pregabalin, and tricyclic antidepressants 2
Special Populations
Renal Impairment
- Use half the usual adult dose if creatinine clearance <70 mL/min/1.73m² 1
- Longer time required to reach steady-state at each dose 1
Hemodialysis
- Topiramate is cleared 4-6 times faster during hemodialysis than in normal individuals 1
- Supplemental dosing may be needed on dialysis days 1
Geriatric Patients
- Dosage adjustment indicated when creatinine clearance ≤70 mL/min/1.73m² 1
Critical Monitoring and Precautions
- Monitor serum bicarbonate regularly due to risk of metabolic acidosis 2, 7
- Taper gradually if discontinuing to avoid increased seizure risk 7
- Contraindicated in pregnancy due to risk of cleft lip/palate; women of childbearing potential require effective contraception 5, 2
- Do not break tablets due to bitter taste 1
- Can be taken without regard to meals 1
- Discontinue phentermine-topiramate ER at least 4 days before procedures requiring general anesthesia due to risk of perioperative complications 2
Common Pitfalls
- Titrating too rapidly increases adverse effects (paresthesia, cognitive impairment, fatigue) 2, 3
- Most dose-limiting adverse events occur during titration phase 8, 9
- Slower titration (25 mg/week) improves tolerability 4, 9
- May require phenytoin dose adjustment when adding topiramate 1
- Combination with other carbonic anhydrase inhibitors increases metabolic acidosis risk 7