Skip to main content

Topiramate (Monograph)

Brand names: Eprontia, Qudexy XR, Topamax, Trokendi XR
Drug class: Anticonvulsants, Miscellaneous
VA class: CN400
Chemical name: 2,3:4,5-bis-O-(1-Methylethylidene)-β-d-fructopyranose sulfamate
Molecular formula: C12H21NO8S
CAS number: 97240-79-4

Medically reviewed by Drugs.com on Apr 26, 2023. Written by ASHP.

Introduction

Anticonvulsant and antimigraine agent; sulfamate-substituted derivative of d-fructose; differs structurally from other currently available anticonvulsant agents.

Uses for Topiramate

Seizure Disorders

Initial monotherapy of partial-onset seizures or primary generalized tonic-clonic seizures in adults and children ≥2 years of age (≥6 years of age for Trokendi XR only).

Adjunctive therapy (i.e., in combination with other anticonvulsants) of partial-onset seizures in adults and children ≥2 years of age (≥6 years of age for Trokendi XR only).

Adjunctive therapy (i.e., in combination with other anticonvulsants) of primary generalized tonic-clonic seizures in adults and children ≥2 years of age (≥6 years of age for Trokendi XR only).

Adjunctive therapy (i.e., in combination with other anticonvulsants) of seizures associated with Lennox-Gastaut syndrome in adults and children ≥2 years of age (≥6 years of age for Trokendi XR only).

Has been used as adjunctive therapy in the treatment of seizures associated with Dravet syndrome [off-label]. Generally used as a second-line anticonvulsant option after clobazam [off-label] and valproic acid [off-label].

Guidelines generally include topiramate among treatment options for adult patients with new-onset focal or generalized epilepsy; however, topiramate has a lower level of recommendation for this indication compared to other therapies (e.g., carbamazepine) due to a lower level of evidence. Topiramate is recommended as monotherapy or adjunctive therapy for management of treatment-resistant epilepsy based on high-quality evidence. The place in therapy for topiramate in the treatment of pediatric epilepsy is not well-defined due to a lack of high-quality evidence.

Migraine Prophylaxis

Prevention of migraine headaches in adults and adolescents ≥12 years of age.

Topiramate is included in guidelines as one of several drugs with established efficacy for migraine prevention in adults. The existing evidence is not sufficient to support superiority of one agent over another; therefore, selection of an appropriate drug should be individualized based on drug efficacy, tolerability, cost, patient comorbidities, and other patient-specific factors. Combining preventive drugs from different classes may be useful when there is a suboptimal response or dose-limiting adverse effects of a particular agent.

Topiramate may also be considered for preventive treatment of migraines in pediatric patients with frequent headaches, disability related to migraine, or medication overuse; however, the evidence supporting topiramate use in this population is of lower quality.

Alcohol Dependence

Has been used in adults for management of alcohol dependence [off-label].

One of several drugs suggested by the American Psychiatric Association for this use. However, additional studies needed to more clearly establish role.

Has been effective in the management of alcohol withdrawal [off-label] in a limited number of patients in uncontrolled studies.

Antipsychotic-induced Weight Gain

Has been used for weight loss and prevention of weight gain from second-generation antipsychotics in patients with schizophrenia.

Binge Eating Disorder

Has been used for the treatment of binge eating disorder,

Essential Tremor

Has been used for the treatment of essential tremor.

Topiramate Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Dispensing and Administration Precautions

Administration

Oral Administration

Administer orally as immediate-release tablets, sprinkle capsules, extended-release capsules, or oral solution without regard to meals.

Sprinkle capsule formulation is bioequivalent to immediate-release tablet and may be substituted as a therapeutic equivalent. Extended-release capsule administered once daily is bioequivalent to immediate-release tablet administered twice daily.

Tablets

Tablets should be swallowed intact and not broken or chewed because of the bitter taste.

Sprinkle Capsules

Swallow capsules whole.

Alternatively, open capsule and sprinkle entire contents on soft food (e.g., applesauce, custard, ice cream, oatmeal, yogurt, pudding); swallow immediately without chewing.

Drinking fluids immediately after administration may help to ensure that all of the mixture is swallowed.

Do not store sprinkle/food mixture for use at a later time.

Extended-release Capsules

Qudexy XR: Swallow capsules whole or, alternatively, open capsule and sprinkle contents on a small amount of soft food; must swallow sprinkle/food mixture immediately without chewing, crushing, or storing for later use.

Trokendi XR: Must swallow capsules whole; do not open and sprinkle on food, crush, or chew; because of these limitations, Trokendi XR is not recommended for use in children <6 years of age.

Oral Solution

Measure the dose using a calibrated measuring device to ensure accuracy; do not measure the dose using a household tablespoon or teaspoon. Discard any unused portion within 30 days after opening.

Standardize 4 Safety (S4S)

A standardized oral liquid concentration for topiramate has been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web]

The topiramate concentration is copyright protected by USP and can be used for internal purposes only.

Standardize 4 Safety Oral Liquid Standard for Topiramate252

Concentration standard

20 mg/mL

Dosage

Pediatric Patients

Seizure Disorders
Monotherapy of Partial-onset Seizures or Primary Generalized Tonic-Clonic Seizures
Oral

Children 2–9 years of age (or 6–9 years of age if using Trokendi XR): Initially, 25 mg daily (administered nightly) for first week. Increase to 50 mg daily (administered in 2 divided doses as immediate-release tablets, or sprinkle capsules, or oral solution, or once daily as extended-release capsules) during second week if tolerated. Subsequently increase by 25–50 mg daily each week as tolerated. Attempt titration to minimum recommended maintenance dosage (see Table 1) over 5–7 weeks. May attempt additional increases (in increments of 25–50 mg daily at weekly intervals) up to maximum recommended dosage (see Table 1) based on tolerability and seizure control.

Table 1. Target Maintenance Topiramate Dosage for Monotherapy of Partial Seizures or Primary Generalized Tonic-Clonic Seizures in Pediatric Patients 2–9 Years of Age1878890

Weight (kg)

Minimum Total Daily Dosage (mg/day)

Maximum Total Daily Dosage (mg/day)

Up to 11

150

250

12–22

200

300

23–31

200

350

32–38

250

350

>38

250

400

Children ≥10 years of age: Initially, 50 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules). Titrate up to recommended dosage of 400 mg daily as tolerated according to schedule in Table 2 or 3. In clinical studies, approximately 58% of patients achieved the maximum dosage of 400 mg daily.

Table 2. Topiramate (Immediate-release Tablets, Sprinkle Capsules, and Oral Solution) Dosage Titration Schedule for Monotherapy of Partial Seizures or Primary Generalized Tonic-Clonic Seizures in Pediatric Patients ≥10 Years of Age190

Week

Morning Dose

Evening Dose

1

25 mg

25 mg

2

50 mg

50 mg

3

75 mg

75 mg

4

100 mg

100 mg

5

150 mg

150 mg

6

200 mg

200 mg

Table 3. Topiramate (Extended-release Capsules) Dosage Titration Schedule for Monotherapy of Partial Seizures or Primary Generalized Tonic-Clonic Seizures in Pediatric Patients ≥10 Years of Age8788

Week

Dosage

1

50 mg once daily

2

100 mg once daily

3

150 mg once daily

4

200 mg once daily

5

300 mg once daily

6

400 mg once daily

Adjunctive Therapy of Partial-onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Seizures Associated with Lennox-Gastaut Syndrome
Oral

Children 2–16 years of age (or 6–16 years of age if using Trokendi XR): Initially, 25 mg (or less based on a range of 1–3 mg/kg daily) given nightly for the first week. Increase dosage at 1- or 2-week intervals in increments of 1–3 mg/kg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules) to achieve optimal clinical response.

Recommended maintenance dosage is approximately 5–9 mg/kg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules).

Alternatively, some clinicians recommend an initial dosage of 0.5–1 mg/kg daily, with slow titration (in increments of 1–3 mg/kg every other week or in increments of 0.5–1 mg/kg per week) to obtain optimal efficacy with minimal adverse effects.

Adjunctive Therapy of Seizures Associated with Dravet Syndrome†
Oral

Initial dosage usually 0.5 to 2 mg/kg daily (in divided doses), increasing to a target dosage of 5–12 mg/kg daily.

Migraine Prophylaxis
Oral

Adolescents ≥12 years of age: Recommended dosage is 100 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules). Titrate therapy using the schedule in Table 4 or 5.

Table 4. Topiramate (Immediate-release Tablets, Sprinkle Capsules, and Oral Solution) Dosage Titration Schedule for Migraine Prophylaxis in Adolescents

Week

Morning Dose

Evening Dose

1

None

25 mg

2

25 mg

25 mg

3

25 mg

50 mg

4

50 mg

50 mg

Table 5. Topiramate (Extended-release Capsules) Dosage Titration Schedule for Migraine Prophylaxis in Adolescents

Week

Dosage

1

25 mg once daily

2

50 mg once daily

3

75 mg once daily

4

100 mg once daily

Titrate dosage based on clinical outcome. Use longer intervals between dose adjustments if required.

Adults

Seizure Disorders
Monotherapy of Partial-onset Seizures or Primary Generalized Tonic-Clonic Seizures
Oral

Initially, 50 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules). Titrate up to recommended dosage of 400 mg daily as tolerated according to schedule in Table 6 or 7, depending on the dosage form used. In clinical studies, approximately 58% of patients achieved the maximum dosage of 400 mg daily.

Table 6. Topiramate (Immediate-release Tablets, Sprinkle Capsules, and Oral Solution) Dosage Titration Schedule for Monotherapy of Partial Seizures or Primary Generalized Tonic-Clonic Seizures in Adults190

Week

Morning Dose

Evening Dose

1

25 mg

25 mg

2

50 mg

50 mg

3

75 mg

75 mg

4

100 mg

100 mg

5

150 mg

150 mg

6

200 mg

200 mg

Table 7. Topiramate (Extended-release Capsules) Dosage Titration Schedule for Monotherapy of Partial Seizures or Primary Generalized Tonic-Clonic Seizures in Adults.8788

Week

Dosage

1

50 mg once daily

2

100 mg once daily

3

150 mg once daily

4

200 mg once daily

5

300 mg once daily

6

400 mg once daily

Adjunctive Therapy of Partial-onset Seizures
Oral

Initially, 25–50 mg daily. Increase dosage at weekly intervals in increments of 25–50 mg to achieve optimal clinical response.

Recommended maintenance dosage is 200–400 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules).

Limited data indicate that titration in increments of 25 mg/week is associated with a lower incidence of cognitive and psychiatric adverse effects and lower discontinuance rates but may delay the time to reach an effective dosage.

Dosages >400 mg daily have not been shown to improve response.

Adjunctive Therapy of Primary Generalized Tonic-Clonic Seizures
Oral

Initially, 25–50 mg daily. Increase dosage at weekly intervals in increments of 25–50 mg to achieve optimal clinical response.

Recommended maintenance dosage is 400 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules).

Limited data indicate that titration in increments of 25 mg/week is associated with a lower incidence of cognitive and psychiatric adverse effects and lower discontinuance rates but may delay the time to reach an effective dosage.

Adjunctive Therapy of Seizures Associated with Lennox-Gastaut Syndrome
Oral

Initially, 25–50 mg daily. Increase dosage at weekly intervals in increments of 25–50 mg to achieve optimal clinical response.

Recommended maintenance dosage is 200–400 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules).

Limited data indicate that titration in increments of 25 mg/week is associated with a lower incidence of cognitive and psychiatric adverse effects and lower discontinuance rates but may delay the time to reach an effective dosage.

Migraine Prophylaxis
Oral

Recommended dosage is 100 mg daily (administered in 2 divided doses as immediate-release tablets, sprinkle capsules, or oral solution, or once daily as extended-release capsules). Titrate therapy using the schedule in Table 8 or 9, depending on the dosage form used.

Table 8. Topiramate (Immediate-release Tablets, Sprinkle Capsules, and Oral Solution) Dosage Titration Schedule for Migraine Prophylaxis in Adults

Week

Morning Dose

Evening Dose

1

None

25 mg

2

25 mg

25 mg

3

25 mg

50 mg

4

50 mg

50 mg

Table 9. Topiramate (Extended-release Capsules) Dosage Titration Schedule for Migraine Prophylaxis in Adults

Week

Dosage

1

25 mg once daily

2

50 mg once daily

3

75 mg once daily

4

100 mg once daily

Titrate dosage based on clinical outcome. Increase intervals between dose adjustments if required.

Alcohol Dependence†

Optimum dosage regimen not established; initial dosage of 25 mg daily followed by gradual titration to maintenance dosage of 200–300 mg daily found to be effective in clinical studies.

Clinical studies suggest that a more gradual titration (e.g., over 8 weeks) may be better tolerated than more rapid titration (e.g., over 6 weeks).

A period of abstinence from alcohol prior to initiating topiramate therapy does not appear to be necessary.

Prescribing Limits

Pediatric Patients

Monotherapy of Partial-onset Seizures or Primary Generalized Tonic-Clonic Seizures
Oral

Pediatric patients 2–9 years of age: Total daily dose should not exceed maximum recommended maintenance dosage for each range of body weight. (See Table 1.)

Adjunctive Therapy of Seizure Disorders
Oral

Pediatric patients 2–16 years of age: Total daily dose should not exceed 400 mg.

Special Populations

Hepatic Impairment

Clearance may be decreased; however, manufacturer makes no specific recommendations regarding dosage adjustment.

Renal Impairment

In patients with renal impairment (Clcr <70 mL/minute per 1.73 m2), decrease daily adult dosage by 50%.

Patients undergoing hemodialysis may require a supplemental dose following dialysis session; determine amount based on duration of dialysis, clearance rate of dialysis system, and the patient’s effective renal clearance of topiramate.

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients.

Cautions for Topiramate

Contraindications

Warnings/Precautions

Acute Myopia and Secondary Closure Glaucoma Syndrome

Acute myopia with secondary angle-closure glaucoma reported. Symptoms (e.g., acute onset of decreased visual acuity and/or ocular pain) typically occur within 1 month of initiating therapy. Discontinue treatment with topiramate as rapidly as possible based on clinical judgment if visual problems occur; additional supportive measures may be indicated.

Visual Field Defects

Visual field defects not associated with elevated intraocular pressure also reported.

If adverse ocular effects or visual problems occur, consider discontinuance of therapy. Manifestations generally resolve after drug is discontinued.

Oligohidrosis and Hyperthermia

Possible oligohidrosis and hyperthermia, particularly in pediatric patients; rarely may require hospitalization.

Monitor patients, particularly pediatric patients, closely for decreased sweating and increased body temperature, particularly in hot weather.

Consider risk of hyperthermia when used concomitantly with other drugs that predispose to heat-related disorders (e.g., carbonic anhydrase inhibitors, drugs with anticholinergic activity).

Metabolic Acidosis

Hyperchloremic, non-anion gap, metabolic acidosis reported. Manifestations may include hyperventilation, nonspecific symptoms (e.g., fatigue, anorexia), cardiac arrhythmias, or stupor. Can occur at any time during therapy.

Potential for serious sequelae (e.g., nephrolithiasis, nephrocalcinosis, osteomalacia and/or osteoporosis with increased risk for fractures, reduced growth rates in pediatric patients) from chronic, untreated metabolic acidosis.

Measure serum bicarbonate concentrations at baseline and periodically during therapy.

If metabolic acidosis develops and persists, consider reducing dosage or discontinuing therapy (by gradually tapering dose). If therapy is continued in patient with persistent acidosis, consider alkali treatment.

Interaction with Alcohol

Trokendi XR contraindicated in patients with recent alcohol use (i.e., within 6 hours prior to or 6 hours after topiramate use); marked elevations in plasma concentrations of Trokendi XR can occur in the presence of alcohol and concentrations may become subtherapeutic later in the day.

Suicidal Behavior and Ideation

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%). Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks. Relative risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.

Balance risk of suicidality with risk of untreated illness. Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality. If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.

Cognitive/Neuropsychiatric Effects

Immediate-release formulations of topiramate have been associated with cognitive and neuropsychiatric adverse events; these effects are thus also expected with extended-release preparations. CNS-related adverse effects are common.

CNS effects are generally classified into 3 categories: cognitive-related dysfunction (confusion, psychomotor slowing, difficulty with concentration/attention, difficulty with memory, speech or language problems), psychiatric/behavioral disturbances (e.g., depression, mood problems), and somnolence and fatigue.

Risk is increased with rapid titration and higher initial dosages.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. (See Pregnancy under Cautions.) In utero exposure to topiramate associated with increased risk of oral cleft birth defects (cleft lip and/or palate) and risk of neonates being small for gestational age.

Developmental toxicity, including teratogenicity and embryotoxicity, structural malformations, and maternal toxicity demonstrated in animals.

Inform all females of reproductive potential of the potential risks to the fetus from exposure to topiramate.

Withdrawal of Antiepileptic Drugs

Discontinue therapy gradually to minimize the potential for increased seizure frequency. Appropriate monitoring recommended if more rapid withdrawal required.

Decrease in Bone Mineral Density

Reductions in bone mineral density in the lumbar spine and total body less head reported among pediatric patients treated with topiramate. Potential impact on fracture risk cannot be determined due to trial limitations.

Negative Effects on Growth (Height and Weight)

Reductions in growth (height and weight) observed in pediatric patients treated with topiramate. Carefully monitor height and weight in pediatric patients receiving long-term treatment with topiramate.

Serious Skin Reactions

Serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred. Discontinue therapy at first sign of drug-related rash; do not resume if symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur.

Hyperammonemia and Encephalopathy (without and with Concomitant Valproic Acid Use)

Dose-related hyperammonemia, with or without encephalopathy, reported. In some cases, ammonia concentrations were markedly increased in patients receiving a topiramate dosage of 100 mg daily.

During postmarketing experience, hyperammonemia with or without encephalopathy reported in patients receiving concomitant topiramate and valproic acid who previously tolerated either drug alone.

Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at increased risk.

Although patients may be asymptomatic, manifestations usually include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. In most cases, manifestations abated following discontinuance of therapy.

If unexplained lethargy, vomiting, or changes in mental status occur, consider possibility of hyperammonemic encephalopathy and measure ammonia concentration.

Kidney Stones

Increased incidence of kidney stone formation in clinical trials in adults; incidence higher in men than women. Kidney stones also reported in pediatric patients.

Avoid use in patients receiving other drugs that produce metabolic acidosis and in those on a ketogenic diet.

Maintain adequate fluid intake to decrease stone formation.

Hypothermia with Concomitant Valproic Acid Use

Hypothermia, with or without hyperammonemia, reported in patients receiving concurrent topiramate and valproic acid therapy. Can occur after initiating topiramate therapy or following dosage increase. Manifestations may include lethargy, confusion, coma, or substantial alterations in other major organ systems (e.g., cardiovascular, respiratory).

If hypothermia occurs, consider discontinuance of topiramate or valproic acid. Since hypothermia also may be a manifestation of hyperammonemia, monitor plasma ammonia concentrations as part of clinical management.

Specific Populations

Pregnancy

Risk of fetal harm.

Carefully consider benefits versus risks in females of reproductive potential, particularly when topiramate is used for conditions not usually associated with permanent injury or death. If use is necessary in a female of reproductive potential, advise patient to use effective contraception; consider alternative therapies in patients who are planning a pregnancy.

Effect of topiramate-induced metabolic acidosis not specifically studied during pregnancy; however, metabolic acidosis during pregnancy is known to cause decreased fetal growth, decreased fetal oxygenation, and fetal death. Monitor pregnant patients for metabolic acidosis in the same manner as nonpregnant patients. In addition, monitor neonates since possible drug transfer and transient metabolic acidosis may occur following birth.

North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or [Web].

Lactation

Distributed into human milk at concentrations similar to those in maternal plasma. Effects of the drug on milk production not known. Diarrhea and somnolence reported in breast-fed infants whose mothers were receiving topiramate.

Consider known benefits of breast-feeding along with the woman’s clinical need for topiramate and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Females and Males of Reproductive Potential

Inform all females of reproductive potential of the potential risks to the fetus from exposure to topiramate. Consider alternative options in patients who are planning a pregnancy. If topiramate is used in a female of reproductive potential who is not planning a pregnancy, recommend use of effective contraception. Consider the potential for decreased efficacy of estrogen-containing oral contraceptives.

Pediatric Use

Safety and efficacy for management of seizure disorders not established in children <2 years of age. Safety and efficacy for migraine prophylaxis not established in pediatric patients <12 years of age.

Although other preparations of topiramate may be used in children as young as 2 years of age for management of seizure disorders, use of Trokendi XR is recommended only in children ≥6 years of age because the capsule formulation must be swallowed whole and cannot be sprinkled on food, crushed, or chewed.

Hyperchloremic, non-anion gap, metabolic acidosis reported.

Metabolic acidosis in patients <2 years of age (not an FDA-labeled population) notably greater in magnitude than that observed in older children and adults. Potential for serious sequelae (e.g., osteomalacia [rickets], reduced growth rates, decrease in maximal height achieved) resulting from chronic, untreated metabolic acidosis.

Measure serum bicarbonate concentrations at baseline and periodically during therapy. Reductions in bone mineral density and growth reported in pediatric patients treated with topiramate.

Incidence of adverse CNS effects appears to be lower in children than adults.

Oligohidrosis and hyperthermia typically reported in children.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.

Clearance may be decreased in patients with reduced renal function. Monitor renal function.

Dosage adjustment may be necessary in geriatric patients with impaired renal function.

Hepatic Impairment

Clearance may be decreased.

Renal Impairment

Clearance decreased; dosage adjustment recommended in patients with moderate or severe renal impairment.

Common Adverse Effects

Adults and pediatric patients in seizure studies (≥10%): Paresthesia, anorexia, weight loss, speech disorders or other related speech problems, fatigue, dizziness, somnolence, nervousness, psychomotor slowing, abnormal vision, fever.

Adults and adolescents in migraine studies (≥5%): Paresthesia, anorexia, weight loss, difficulty with memory, taste perversion, diarrhea, hypoesthesia, nausea, abdominal pain, upper respiratory tract infection.

Adults receiving dosages ≤300 mg daily for alcohol dependence: Paresthesia, taste perversion, fatigue, anorexia, insomnia, concentration and attention difficulties, memory impairment, nervousness, somnolence, diarrhea, dizziness, pruritus.

Drug Interactions

Mild inhibitor of CYP2C19 and mild inducer of CYP3A4.

Does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, or 3A4/5.

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions with drugs metabolized by CYP2C19 or CYP3A4 are possible.

Drugs Predisposing to Heat-related Disorders

Potential pharmacologic interaction (increased risk of hyperthermia) with drugs that predispose to heat-related disorders; use with caution.

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potential for additive CNS effects

Trokendi XR extended-release capsules: In vitro data indicate that topiramate plasma concentrations may be markedly increased soon after dosing and become subtherapeutic later in the day

Use caution

Use of Trokendi XR contraindicated in patients with recent alcohol use (i.e., within 6 hours prior to or 6 hours after topiramate use)

Amitriptyline

Increased plasma amitriptyline concentrations

Adjust amitriptyline dosage based on clinical response

Anticholinergic agents

Possible increased risk of hyperthermia

Carbamazepine

Clinically important decreases in plasma concentrations of topiramate observed; plasma concentrations of carbamazepine or its active metabolite not substantially altered

Dosage adjustment may be required

Carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide, zonisamide)

Possible increased risk or severity of metabolic acidosis and kidney stone formation; possible increased risk of hyperthermia

Monitor for onset or worsening of metabolic acidosis

CNS depressants

Potential for enhanced CNS depression

Use with extreme caution

Digoxin

Possible decrease in serum digoxin concentrations

Clinical importance unknown

Dihydroergotamine

Pharmacokinetic interaction unlikely

Diltiazem

Possible decreased plasma diltiazem concentrations and increased topiramate concentrations

Glyburide

Possible decrease in plasma glyburide concentrations

Haloperidol

No effect on pharmacokinetics of haloperidol

Hydrochlorothiazide

Possible increased plasma topiramate concentrations; pharmacokinetics of hydrochlorothiazide not substantially altered

Enhanced risk of hypokalemia

Although clinical importance of this interaction not known, topiramate dosage adjustment may be necessary when hydrochlorothiazide is initiated

Lamotrigine

Decreased plasma topiramate concentrations; lamotrigine concentrations not likely to be affected by concurrent administration of up to 400 mg daily of topiramate

Lithium

Possible increased exposure to lithium with concurrent administration of high-dose (up to 600 mg daily) topiramate

Monitor serum lithium concentrations in patients receiving concurrent lithium and high-dose topiramate therapy

Metformin

Possible increase in plasma metformin concentrations; possible decrease in topiramate clearance

Clinical importance of these pharmacokinetic effects unknown; however, topiramate can cause metabolic acidosis, a condition for which the use of metformin is contraindicated

Oral contraceptives

Substantial decrease in ethinyl estradiol exposure reported in patients receiving an oral contraceptive containing ethinyl estradiol and norethindrone in conjunction with topiramate and valproic acid

Consider possibility of decreased oral contraceptive efficacy and breakthrough bleeding

Phenobarbital

<10% change in plasma concentrations of phenobarbital

Phenytoin

Clinically important decreases in plasma topiramate concentrations observed; possible increase in serum phenytoin concentrations (generally in those receiving twice-daily phenytoin regimen)

Dosage adjustment may be required

Pioglitazone

Decreased systemic exposure to active metabolites of pioglitazone; however, clinical importance not known

When topiramate therapy is initiated in patients receiving pioglitazone or vice versa, monitor blood glucose control carefully

Primidone

<10% change in plasma concentrations of primidone

Propranolol

Pharmacokinetic interaction unlikely

Risperidone

Decreased plasma risperidone concentrations; increased plasma topiramate concentrations

No clinically important changes observed

Sumatriptan

No effect on pharmacokinetics of sumatriptan

Valproic acid

Possible decrease in plasma concentrations of valproic acid and topiramate

Concomitant use associated with hyperammonemia with or without encephalopathy; also associated with hypothermia (with or without hyperammonemia)

Consider discontinuance of topiramate or valproic acid if hypothermia occurs

Venlafaxine

Pharmacokinetics of venlafaxine or topiramate not affected

Warfarin

Decreased INR and PT observed with concomitant use

Topiramate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations achieved in about 2 hours (following administration of tablets or sprinkle capsules), 30 minutes (following administration of the oral solution) or 20–24 hours (following administration of extended-release formulations).

Sprinkle capsule formulation is bioequivalent to immediate-release tablet. At steady state, extended-release capsules administered once daily are bioequivalent to immediate-release tablets administered twice daily.

Food

Food may affect time to peak concentrations (depending on formulation), but does not appear to affect systemic exposure.

Distribution

Extent

Appears to cross the placenta.

Distributes into breast milk.

Plasma Protein Binding

Approximately 15–41%. Fraction bound decreases with increasing plasma topiramate concentrations.

Elimination

Metabolism

Not extensively metabolized. Six minor metabolites identified; none constitutes more than 5% of administered dose.

Elimination Route

Eliminated principally in urine as unchanged drug (approximately 70%).

Half-life

Immediate-release tablets, sprinkle capsules, oral solution: Approximately 21 hours.

Extended-release capsules (Trokendi XR): Approximately 31 hours.

Extended-release capsules (Qudexy XR): Approximately 56 hours.

Special Populations

In pediatric patients, clearance is 50% higher, resulting in a shorter elimination half-life and lower plasma concentrations, relative to adults.

In geriatric patients with reduced renal function (Clcr reduced by 20% compared with younger adults), clearance was decreased.

In patients with hepatic impairment, clearance may be decreased; mechanism not fully understood.

In patients with moderate or severe renal impairment, clearance is reduced by 42 or 54%, respectively. In patients undergoing hemodialysis, clearance is 4–6 times more rapid than in healthy individuals.

Stability

Storage

Oral

Extended-release Capsules

Qudexy XR: Tight containers at 20–25°C (excursions permitted to 15–30°C). Protect from moisture.

Trokendi XR: Tight containers at 25°C (excursions permitted to 15–30°C). Protect from moisture and light.

Sprinkle Capsules

Tight containers at ≤25°C. Protect from moisture.

Tablets

Tight containers at 15–30°C. Protect from moisture.

Oral Solution

20–25°C (excursions permitted to 15–30°C). Discard unused portion 30 days after first opening.

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Topiramate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules (containing coated particles)

15 mg*

Topamax Sprinkle Capsules

Janssen

Topiramate Sprinkle Capsules

25 mg*

Topamax Sprinkle Capsules

Janssen

Topiramate Sprinkle Capsules

Capsules, extended-release

25 mg*

Qudexy XR

Upsher-Smith

Topiramate Extended-release Capsules

Trokendi XR

Supernus

50 mg*

Qudexy XR

Upsher-Smith

Topiramate Extended-release Capsules

Trokendi XR

Supernus

100 mg*

Qudexy XR

Upsher-Smith

Topiramate Extended-release Capsules

Trokendi XR

Supernus

150 mg*

Qudexy XR

Upsher-Smith

Topiramate Extended-release Capsules

200 mg*

Qudexy XR

Upsher-Smith

Topiramate Extended-release Capsules

Trokendi XR

Supernus

Solution

25 mg/mL

Eprontia

Azurity

Tablets, film-coated

25 mg*

Topamax

Janssen

Topiramate Tablets

50 mg*

Topamax

Janssen

Topiramate Tablets

100 mg*

Topamax

Janssen

Topiramate Tablets

200 mg*

Topamax

Janssen

Topiramate Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 26, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

Reload page with references included

Frequently asked questions

View more FAQ