Drug Monograph
Topiramate
Topamax
Pharmacokinetic Profile
Half-Life
19–25 h (monotherapy); 9–12 h with enzyme inducers
Metabolism
Minimal hepatic (~15–20%); hydroxylation, hydrolysis, glucuronidation
Protein Binding
13–17% (low)
Bioavailability
80–95% (oral; unaffected by food)
Volume of Distribution
0.6–0.8 L/kg
Clinical Information
Drug Class
Sulfamate-substituted monosaccharide anticonvulsant; carbonic anhydrase inhibitor
Available Doses
Tablets: 25, 50, 100, 200 mg; Sprinkle Capsules: 15, 25 mg
Route
Oral
Renal Adjustment
CrCl <70: reduce dose by 50%
Hepatic Adjustment
Levels may increase; mechanism unclear; use with caution
Pregnancy
Teratogenic — oral clefts, SGA risk
Lactation
Excreted in breast milk; use with caution
Schedule / Legal Status
Rx only (not scheduled)
Generic Available
Yes
Topiramate Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Partial-onset seizures | ≥2 years | Monotherapy or adjunctive | FDA Approved |
| Primary generalized tonic-clonic seizures | ≥2 years | Monotherapy or adjunctive | FDA Approved |
| Lennox-Gastaut syndrome | ≥2 years | Adjunctive | FDA Approved |
| Migraine prevention | ≥12 years | Preventive monotherapy | FDA Approved |
Topiramate is a second-generation broad-spectrum anticonvulsant approved by the FDA in 1996. Its multiple mechanisms of action make it effective across several seizure types. The migraine prevention indication was expanded in 2025 to include patients 12 years and older (previously adults only). Topiramate is also a component of the combination product Qsymia (phentermine/topiramate ER) for chronic weight management, though this indication falls under a separate product label.
Off-Label Uses
Alcohol use disorder: Reduces heavy drinking days and promotes abstinence; supported by RCTs. Evidence quality: Moderate (APA guidelines mention topiramate as an option).
Binge eating disorder: Reduces binge frequency and promotes weight loss. Evidence quality: Moderate (placebo-controlled trials).
Essential tremor: Second-line option when beta-blockers and primidone are inadequate. Evidence quality: Moderate (RCTs available).
Neuropathic pain / diabetic neuropathy: Limited evidence for efficacy. Evidence quality: Low.
Cluster headache prophylaxis: Case series only. Evidence quality: Very Low.
Topiramate Dosing
Epilepsy — Monotherapy (Adults & ≥10 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Partial-onset or GTCS — new diagnosis, monotherapy | 25 mg BID (Week 1) | 200 mg BID (400 mg/day) | 400 mg/day | Titrate per FDA PI Table 1: increase by 50 mg/day weekly for weeks 1–4, then by 100 mg/day for weeks 5–6 Can be taken without regard to meals; do not break tablets (bitter taste) |
Epilepsy — Adjunctive Therapy
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Partial-onset seizures or LGS — adults (≥17 y) | 25–50 mg/day | 200–400 mg/day in 2 divided doses | 400 mg/day | Titrate by 25–50 mg/day weekly; doses >400 mg/day have not shown additional benefit for partial-onset seizures Slower titration (25 mg/week) reduces cognitive side effects |
| GTCS — adults (≥17 y), adjunctive | 25–50 mg/day | 400 mg/day in 2 divided doses | 400 mg/day | Same titration schedule as partial-onset seizures |
| Epilepsy — pediatric adjunctive (2–16 y) | 25 mg nightly (or 1–3 mg/kg/day) | 5–9 mg/kg/day in 2 divided doses | 400 mg/day | Titrate by 1–3 mg/kg/day at 1–2 week intervals Sprinkle capsule formulation available for younger children |
Migraine Prevention (≥12 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Migraine prophylaxis — episodic or chronic | 25 mg nightly (Week 1) | 50 mg BID (100 mg/day) | 100 mg/day | Titrate by 25 mg/day weekly over 4 weeks (FDA PI Table 3); not indicated for acute migraine treatment Some patients respond to 50 mg/day; higher doses increase side effects without added migraine benefit |
Special Populations
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Renal impairment (CrCl <70 mL/min) | 50% of usual dose | 50% of usual dose | 50% of usual max | Topiramate clearance reduced; accumulation risk Monitor for adverse effects; slower titration advisable |
| Hemodialysis supplement | Supplemental dose after dialysis | Topiramate is cleared by dialysis; supplement based on dialysis duration and clearance rate | ||
Clinical Pearl: Slow Titration Reduces Cognitive Side Effects
Cognitive adverse reactions (word-finding difficulty, psychomotor slowing, concentration problems) are the most functionally disabling effects of topiramate and are strongly correlated with titration speed and dose. In migraine trials, titrating by 25 mg/day weekly (the recommended schedule) produced substantially fewer cognitive complaints than faster titration used in older epilepsy trials (100–200 mg/day weekly increments). At the recommended migraine dose of 100 mg/day with standard titration, cognitive complaints affected approximately 22% of patients compared to 10% on placebo (FDA PI).
Topiramate Pharmacology
Mechanism of Action
Topiramate has multiple mechanisms that contribute to its broad-spectrum anticonvulsant and migraine-preventive effects. It blocks voltage-dependent sodium channels, reducing sustained high-frequency neuronal firing. It enhances GABA-A receptor activity at a non-benzodiazepine, non-barbiturate site, increasing chloride channel opening frequency. It antagonizes glutamate at AMPA/kainate receptors, reducing excitatory neurotransmission. Additionally, topiramate weakly inhibits carbonic anhydrase (isoenzymes II and IV), which contributes to its metabolic acidosis profile, kidney stone risk, and paresthesia side effects. The combination of these mechanisms — dampening excitatory pathways while enhancing inhibitory tone — underpins its efficacy across focal, generalized, and Lennox-Gastaut seizure types and in migraine prevention.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability 80–95%; Tmax 2–4 h; food delays but does not reduce absorption | Can be dosed without regard to meals; rapid and predictable onset of absorption |
| Distribution | Vd 0.6–0.8 L/kg; protein binding 13–17%; saturable binding to erythrocyte carbonic anhydrase | Low protein binding eliminates displacement-type interactions (unlike phenytoin/valproate); free drug monitoring rarely needed |
| Metabolism | Minimal hepatic metabolism (~15–20% of dose); six inactive metabolites via hydroxylation, hydrolysis, glucuronidation; fraction metabolized increases to ~50% with enzyme-inducing AEDs | Enzyme inducers (phenytoin, carbamazepine) increase topiramate clearance by up to 50%, potentially requiring higher doses; topiramate itself is a weak CYP2C19 inhibitor and mild CYP3A4 inducer |
| Elimination | t½ 19–25 h (monotherapy), 9–12 h (with enzyme inducers); 70–80% excreted unchanged in urine; renal clearance ~14 mL/min (tubular reabsorption) | Linear kinetics allow predictable dose-concentration relationship; twice-daily dosing adequate; reduce dose by 50% in renal impairment (CrCl <70); supplemental dosing required after hemodialysis |
Topiramate Side Effects
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Paresthesia (tingling in extremities) | 35–51% | Dose-dependent; related to carbonic anhydrase inhibition and metabolic acidosis; usually mild and may attenuate over weeks |
| Fatigue / asthenia | 14–19% | More common during titration; dose-related; may persist into maintenance phase |
| Anorexia / decreased appetite | 11–14% | Dose-dependent; contributes to weight loss effect; monitor nutritional status in pediatric patients |
| Dizziness | 10–15% | Usually transient; more frequent with rapid titration; advise caution with driving |
| Weight loss | 5–16% | Dose- and duration-dependent; mean 2–6 kg over 6 months at therapeutic doses; higher baseline weight predicts greater loss |
| Cognitive dysfunction (word-finding, psychomotor slowing) | 10–28% | Most disabling side effect; strongly dose- and titration-rate dependent; higher at >400 mg/day; verbal fluency most affected |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Somnolence | 7–10% | Dose-related; most common during titration |
| Nausea | 6–10% | May improve by taking with food; dose-related |
| Diarrhea | 9–11% | Generally self-limiting |
| Taste perversion (dysgeusia) | 7–19% | Carbonated beverages commonly taste altered; dose-dependent |
| Difficulty with memory | 7–11% | Part of the broader cognitive profile; dose-dependent; often attenuates but may persist |
| Difficulty with concentration / attention | 3–10% | Dose-dependent; worse during titration (3–9%) than maintenance (~1%) |
| Nervousness / anxiety | 3–8% | May contribute to discontinuation; dose-related |
| Depression / mood problems | 3–9% | Dose-related; monitor for suicidal ideation (AED class warning) |
| Speech disorders / language problems | 3–7% | Word-finding difficulty is the hallmark cognitive complaint of topiramate |
Serious
Serious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Metabolic acidosis (hyperchloremic, non-anion gap) | 23–67% (dose-dependent) | Any time during treatment | Measure baseline and periodic serum bicarbonate; if persistent, reduce dose or discontinue; consider alkali treatment if continuing. |
| Acute myopia / secondary angle-closure glaucoma | Rare | Typically within 1 month of initiation | Discontinue topiramate immediately; ophthalmology referral; standard glaucoma treatments (e.g., miotics) may worsen condition. |
| Oligohidrosis / hyperthermia | Uncommon (mainly pediatric) | Variable; hot weather exposure | Monitor body temperature and sweating in children; ensure adequate hydration; consider discontinuation if severe. |
| Kidney stones (nephrolithiasis) | 1.5% (2–4x untreated) | Months to years | Increase fluid intake; avoid combination with other carbonic anhydrase inhibitors or ketogenic diet; evaluate if renal colic symptoms appear. |
| Hyperammonemia / encephalopathy (especially with valproate) | 14–26% (dose-dependent; higher with VPA) | Variable | Measure ammonia level if lethargy, vomiting, or mental status changes; discontinue if encephalopathy occurs. |
| Hypothermia (with concomitant valproic acid) | Rare | Variable | Monitor core temperature when co-prescribed with valproate; can occur with or without hyperammonemia. |
| Decreased bone mineral density (pediatric) | Documented in pediatric trials | Months of chronic use | Correlated with metabolic acidosis severity; monitor growth and consider DEXA in long-term pediatric users. |
| Fetal toxicity (oral clefts, SGA) | Oral clefts ~1.4%; SGA dose-dependent | First trimester exposure | Counsel women of childbearing potential; effective contraception required; if pregnancy planned, consider alternative agent. |
Discontinuation
Discontinuation Rates
Adjunctive Epilepsy (200–400 mg/day)
~11%
Top reasons: Somnolence, dizziness, anxiety, concentration difficulty, fatigue, paresthesia; rate increases above 400 mg/day
Monotherapy Epilepsy (400 mg/day)
~21%
Top reasons: Memory difficulty, fatigue, insomnia, somnolence, paresthesia
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Cognitive effects (memory, concentration, word-finding) | 3–6% | Most common reason overall; strongly dose-related; often the deciding factor for patients |
| Fatigue / somnolence | 2–4% | More common during titration; may improve with dose stabilization |
| Paresthesia | 2–3% | Despite high incidence, most patients tolerate tingling; rarely the primary reason for stopping |
| Mood / psychiatric effects | 1–3% | Depression, anxiety, nervousness; dose-related |
Managing Cognitive Side Effects
Cognitive dysfunction — particularly word-finding difficulty, psychomotor slowing, and impaired verbal fluency — is the most functionally limiting adverse effect of topiramate. Risk is strongly dose-dependent and titration-rate-dependent. To minimize impact, titrate slowly (25 mg/day weekly increments), use the lowest effective dose, and educate patients that many cognitive effects improve during the maintenance phase. If cognitive complaints are persistent and disabling, dose reduction or switching to an alternative agent (e.g., valproate for epilepsy, propranolol for migraine) should be considered.
Topiramate Drug Interactions
Topiramate has a relatively modest interaction profile compared to older anticonvulsants due to its low protein binding and predominantly renal elimination. However, clinically important interactions exist: enzyme-inducing AEDs reduce topiramate levels by up to 50%, topiramate mildly induces CYP3A4 (reducing estrogen exposure from oral contraceptives), and it weakly inhibits CYP2C19. The combination with valproate warrants particular attention due to the risk of hyperammonemia.
MajorValproic Acid / Divalproex
MechanismBoth inhibit carbonic anhydrase; VPA inhibits topiramate clearance; topiramate may increase ammonia production via unclear mechanism
EffectHyperammonemia with or without encephalopathy; hypothermia; VPA levels may decrease ~11%
ManagementMonitor ammonia levels if altered mental status; monitor core temperature; consider topiramate alternatives if hyperammonemia recurs
FDA PIMajorCombined Oral Contraceptives
MechanismTopiramate induces CYP3A4 metabolism of ethinyl estradiol at doses >200 mg/day (18–30% decrease in EE exposure); minimal effect at ≤200 mg/day
EffectReduced contraceptive efficacy and increased breakthrough bleeding, especially at doses >200 mg/day
ManagementAt ≤200 mg/day topiramate: monitor for breakthrough bleeding. At >200 mg/day: use higher-estrogen OCP (≥50 mcg EE) or non-hormonal contraception
FDA PIModeratePhenytoin / Carbamazepine
MechanismEnzyme inducers increase hepatic metabolism of topiramate by up to 50%, reducing its half-life to 9–12 h; topiramate may modestly increase phenytoin levels
EffectReduced topiramate efficacy due to lower plasma levels
ManagementMay need higher topiramate doses (guided by clinical response); monitor phenytoin levels when adding or removing topiramate
FDA PIModerateLithium
MechanismTopiramate 100 mg every 12 hours (200 mg/day) decreased lithium AUC by ~20% in healthy volunteers
EffectPotential subtherapeutic lithium levels at high topiramate doses
ManagementMonitor lithium levels when co-administered with high-dose topiramate; adjust lithium dose as needed
FDA PIModerateOther Carbonic Anhydrase Inhibitors (e.g., acetazolamide, zonisamide)
MechanismAdditive carbonic anhydrase inhibition
EffectIncreased risk of metabolic acidosis, kidney stones, and oligohidrosis
ManagementAvoid combination when possible; if combined, monitor serum bicarbonate closely and ensure adequate hydration
FDA PIModerateHydrochlorothiazide (HCTZ)
MechanismHCTZ increases topiramate Cmax by 27% and AUC by 29%
EffectIncreased topiramate exposure and potential for dose-dependent adverse effects
ManagementMonitor for increased topiramate side effects when HCTZ is added; dose adjustment may be needed
FDA PIMinorCNS Depressants / Alcohol
MechanismAdditive CNS depression
EffectEnhanced sedation, cognitive impairment, and psychomotor slowing
ManagementCounsel patients to avoid or minimize alcohol; exercise caution with concurrent sedative medications
FDA PIMinorPioglitazone
MechanismTopiramate inhibits CYP2C19, reducing pioglitazone clearance; pioglitazone decreases topiramate AUC by ~15%
EffectModest bidirectional PK changes; generally not clinically significant at standard doses
ManagementMonitor glycemic control; dose adjustment rarely needed
FDA PITopiramate Monitoring
-
Serum Bicarbonate
Baseline, then periodically
Routine Topiramate causes hyperchloremic, non-anion gap metabolic acidosis via carbonic anhydrase inhibition. Average bicarbonate decrease is ~4 mEq/L at 400 mg/day. If persistent acidosis develops, reduce dose, discontinue, or consider alkali supplementation. -
Renal Function
Baseline, then periodically
Routine Topiramate is primarily renally eliminated. Dose reduction required if CrCl <70 mL/min. Monitor for nephrolithiasis symptoms (flank pain, haematuria). -
Cognitive Function
Each visit during titration, then periodically
Routine Screen actively for word-finding difficulty, psychomotor slowing, memory impairment, and concentration problems. These effects are dose-related and may not be spontaneously reported. Consider dose reduction if functionally limiting. -
Ammonia Level
If altered mental status or encephalopathic signs
Trigger-based Particularly important when co-prescribed with valproic acid. Hyperammonemia can be asymptomatic; measure ammonia if lethargy, vomiting, or confusion develop. -
Ophthalmologic Assessment
If visual symptoms arise
Trigger-based Acute myopia with secondary angle-closure glaucoma can occur within the first month. Any acute decrease in visual acuity or ocular pain requires urgent assessment. Visual field defects have also been reported. -
Body Temperature / Sweating (Pediatric)
Ongoing, especially in hot weather
Routine Oligohidrosis and hyperthermia risk is highest in children. Counsel parents to monitor sweating and core temperature in warm environments. -
Growth (Pediatric)
Every 3–6 months (long-term therapy)
Routine Topiramate can slow height and weight gain in children. Chronic metabolic acidosis may reduce growth rates and bone mineral density. Monitor height, weight, and consider DEXA scanning. -
Mood / Suicidality
Each visit, especially early in therapy
Routine AED class-wide suicidality risk; depression and mood problems are dose-related with topiramate. Screen for depression, anxiety, and behavioral changes at every visit.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to topiramate or any excipient in the formulation (standard clinical practice; the 2025 FDA PI Section 4 formally lists no contraindications, but hypersensitivity universally precludes use)
Relative Contraindications (Specialist Input Recommended)
- Pregnancy or planned pregnancy — increased risk of oral clefts (~1.4%) and SGA; effective contraception should be used; discuss risk-benefit if topiramate is medically necessary
- History of nephrolithiasis — topiramate increases kidney stone risk 2–4x via carbonic anhydrase inhibition; weigh benefits against stone recurrence risk
- Severe hepatic impairment — plasma concentrations may be unpredictably elevated
- Pre-existing metabolic acidosis — topiramate will worsen acidosis; closely monitor bicarbonate
- Concurrent valproic acid — increased risk of hyperammonemia, encephalopathy, and hypothermia
Use with Caution
- Renal impairment (CrCl <70 mL/min) — reduce dose by 50%; topiramate accumulation risk
- Elderly patients — more likely to have reduced renal function; may need dose adjustment
- Patients on ketogenic diet — combined acidosis and stone risk with topiramate
- Hot weather / vigorous exercise (children) — oligohidrosis risk; ensure hydration
- Abrupt withdrawal — may precipitate seizures even in patients without epilepsy; always taper gradually
FDA Fetal Toxicity Warning
Fetal Toxicity
Topiramate can cause fetal harm. Data from pregnancy registries show increased risk of major congenital malformations, including cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA). SGA appears dose-dependent and is greater in infants of women who continued topiramate into the third trimester. Animal studies confirm craniofacial defects at clinically relevant doses. Women of childbearing potential should use effective contraception. If pregnancy is planned, discuss switching to an alternative agent with lower teratogenic risk.
FDA Class-Wide Regulatory Warning
Suicidality with Antiepileptic Drugs
All AEDs, including topiramate, carry an increased risk of suicidal thoughts and behavior (approximately 2x placebo risk). Patients should be monitored for emergence of depression, suicidal ideation, or unusual behavioral changes, particularly during early months of therapy and after dose adjustments.
Patient Counselling
Purpose of Therapy
Topiramate is a medication that helps prevent seizures or reduce migraine frequency. It works by calming overactive electrical signals in the brain. It does not cure epilepsy or migraine but provides ongoing protection when taken regularly. The dose is started low and increased gradually to reduce side effects.
How to Take
Take topiramate at the same times each day (usually morning and evening), with or without food. Swallow tablets whole — do not break or chew them as the taste is very bitter. If using sprinkle capsules for a child, the capsule can be opened and the contents sprinkled onto a teaspoon of soft food, then swallowed immediately without chewing. Drink plenty of water throughout the day to reduce kidney stone risk.
Thinking & Memory Changes
Tell patientYou may notice difficulty finding the right words, slower thinking, or trouble concentrating. These effects are most noticeable when the dose is being increased and often improve once the dose is stable. They are worse at higher doses.
Call prescriberIf thinking problems are severe enough to interfere with work, school, or daily tasks, or if they do not improve after 4–6 weeks at a stable dose.
Tingling Sensations (Paresthesia)
Tell patientTingling in the hands, feet, or around the mouth is very common and is usually mild. It tends to be more noticeable at higher doses and often improves with time. Staying well hydrated may help.
Call prescriberIf tingling is severe, painful, or accompanied by numbness or weakness.
Weight Loss & Appetite Changes
Tell patientReduced appetite and weight loss are common effects. While some patients welcome this, unintended significant weight loss should be discussed. Ensure adequate nutrition, especially in children.
Call prescriberIf you lose more than 5–10% of your body weight unintentionally, or if a child is not growing or gaining weight as expected.
Eye Problems
Tell patientRarely, topiramate can cause sudden blurred vision or eye pain, usually within the first month. This is a medical emergency related to increased pressure inside the eye.
Call prescriberSeek immediate medical attention for any sudden decrease in vision or eye pain.
Pregnancy & Contraception
Tell patientTopiramate can cause birth defects, especially cleft lip and palate. Women who could become pregnant must use effective contraception. At higher doses, topiramate may reduce the effectiveness of hormonal contraceptives.
Call prescriberIf you become pregnant, plan to become pregnant, or miss a period. Do not stop topiramate on your own — discuss alternative medications with your prescriber first.
Kidney Stones & Hydration
Tell patientTopiramate increases the risk of kidney stones. Drink at least 6–8 glasses of water daily. Avoid dehydration, especially in hot weather or during exercise.
Call prescriberIf you experience severe flank pain, blood in the urine, or difficulty urinating.
Overheating in Children
Tell patientChildren taking topiramate may sweat less than normal, which can lead to dangerous overheating, especially in hot weather. Ensure your child stays cool and well-hydrated.
Call prescriberIf your child develops a high temperature, appears flushed, or stops sweating during hot weather or physical activity.
Sources
Regulatory (PI / SmPC)
- Janssen Pharmaceuticals, Inc. TOPAMAX (topiramate) Tablets and Sprinkle Capsules — Full Prescribing Information. Revised March 2025. FDA Label Primary source for all FDA-approved indications, dosing schedules, contraindications, warnings, and adverse reaction incidence data.
- Vivus Inc. QSYMIA (phentermine and topiramate extended-release) — Full Prescribing Information. Revised 2024. FDA Label Source for topiramate safety data in the weight management context and hyperammonemia incidence data in adolescents.
Key Clinical Trials
- Silberstein SD, Neto W, Schmitt J, Jacobs D. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61(4):490-495. doi:10.1001/archneur.61.4.490 Pivotal RCT establishing topiramate 100 mg/day as the optimal dose for migraine prevention, with dose-dependent adverse effects.
- Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790-799. doi:10.1056/NEJMoa0902014 Major pediatric epilepsy trial contextualizing topiramate among second-generation AEDs for childhood seizure disorders.
- Kramer CK, Leitao CB, Pinto LC, Canani LH, Azevedo MJ, Gross JL. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev. 2011;12(5):e338-347. doi:10.1111/j.1467-789X.2010.00846.x Meta-analysis of 10 RCTs (3,320 participants) quantifying topiramate-associated weight loss and adverse event rates.
Guidelines
- Silberstein SD. Topiramate in migraine prevention: a 2016 perspective. Headache. 2017;57(1):165-178. doi:10.1111/head.12997 Comprehensive clinical review positioning topiramate in migraine prevention algorithms with evidence synthesis and practical guidance.
- Oskoui M, Pringsheim T, Billinghurst L, et al. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention. Neurology. 2019;93(11):500-509. doi:10.1212/WNL.0000000000008105 AAN/AHS guideline for pediatric migraine prevention — Level B recommendation for topiramate in children and adolescents.
- Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I and II. Neurology. 2018;91(2):74-81. doi:10.1212/WNL.0000000000005756 AAN/AES guideline comparing newer AEDs — supports topiramate as effective for focal and generalized seizures.
Mechanistic / Basic Science
- Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41(Suppl 1):S3-S9. doi:10.1111/j.1528-1157.2000.tb02163.x Foundational review of topiramate’s multiple mechanisms of action: sodium channel blockade, GABA enhancement, glutamate antagonism, and carbonic anhydrase inhibition.
- Mula M. Topiramate and cognitive impairment: evidence and clinical implications. Ther Adv Drug Saf. 2012;3(6):279-289. doi:10.1177/2042098612455357 Review of topiramate cognitive side effects with discussion of risk factors, dose-response relationships, and management strategies.
Pharmacokinetics / Special Populations
- Perucca E. Pharmacokinetic profile of topiramate in comparison with other new antiepileptic drugs. Epilepsia. 2003;44(Suppl 4):8-17. doi:10.1046/j.1528-1157.44.s4.2.x Definitive PK review: bioavailability, protein binding, linear kinetics, renal elimination, and effect of enzyme-inducing co-medications on topiramate clearance.
- Doose DR, Walker SA, Gisclon LG, Nayak RK. Single-dose pharmacokinetics and effect of food on the bioavailability of topiramate. J Clin Pharmacol. 1996;36(10):884-891. doi:10.1002/j.1552-4604.1996.tb04756.x Primary PK study establishing topiramate’s dose-proportional kinetics, t½ of ~21 h, and lack of clinically significant food effect on bioavailability.
- Manitpisitkul P, Curtin CR, Shalayda K, et al. Pharmacokinetics of topiramate in patients with renal impairment, end-stage renal disease undergoing hemodialysis, or hepatic impairment. Epilepsy Res. 2014;108(5):891-901. doi:10.1016/j.eplepsyres.2014.03.001 PK study in special populations confirming 50% dose reduction in renal impairment and providing hemodialysis supplementation data.