Monotherapy Epilepsy

TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate capsules) Sprinkle Capsules are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. Safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see Clinical Studies].

Adjunctive Therapy Epilepsy

TOPAMAX® Tablets and TOPAMAX® Sprinkle Capsules are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome [see Clinical Studies].

Migraine

TOPAMAX® Tablets and TOPAMAX® Sprinkle Capsules are indicated for adults for the prophylaxis of migraine headache [see Clinical Studies]. The usefulness of TOPAMAX® in the acute treatment of migraine headache has not been studied.

Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize TOPAMAX® (topiramate) therapy.

On occasion, the addition of TOPAMAX® to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with TOPAMAX® may require adjustment of the dose of TOPAMAX® .

Because of the bitter taste, tablets should not be broken.

TOPAMAX® can be taken without regard to meals.

Monotherapy Use

Adults and Pediatric Patients 10 Years and Older

The recommended dose for TOPAMAX® monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1):

Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older

Children Ages 2 to < 10 Years

Dosing of topiramate as initial monotherapy in children 2 to < 10 years of age with partial onset or primary generalized tonic-clonic seizures was based on a pharmacometric bridging approach [see Clinical Studies].

Dosing in patients 2 to < 10 years is based on weight. During the titration period, the initial dose of TOPAMAX® should be 25 mg/day administered nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. Dosage can be increased by 25-50 mg/day each subsequent week as tolerated. Titration to the minimum maintenance dose should be attempted over 5-7 weeks of the total titration period. Based upon tolerability and seizure control, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25-50 mg/day weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (Table 2).

Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to < 10 Years

Adjunctive Therapy Use

Adults 17 Years of Age and Over - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of TOPAMAX® as adjunctive therapy in adults with partial onset seizures is 200 to 400 mg/day in two divided doses, and 400 mg/day in two divided doses as adjunctive treatment in adults with primary generalized tonic-clonic seizures. It is recommended that therapy be initiated at 25 to 50 mg/day followed by titration to an effective dose in increments of 25 to 50 mg/day every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day (600, 800 or 1,000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose was reached at the end of 8 weeks [see Clinical Studies].

Pediatric Patients Ages 2 - 16 Years – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of TOPAMAX® as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose of 6 mg/kg/day was reached at the end of 8 weeks [see Clinical Studies].

Migraine

The recommended total daily dose of TOPAMAX® as treatment for adults for prophylaxis of migraine headache is 100 mg/day administered in two divided doses (Table 3). The recommended titration rate for topiramate for migraine prophylaxis to 100 mg/day is:

Table 3: Migraine Prophylaxis Titration Schedule for Adults

Dose and titration rate should be guided by clinical outcome. If required, longer intervals between dose adjustments can be used.

TOPAMAX® can be taken without regard to meals.

Administration of TOPAMAX® Sprinkle Capsules

TOPAMAX® (topiramate capsules) Sprinkle Capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoon) of soft food. This drug/food mixture should be swallowed immediately and not chewed. It should not be stored for future use.

Patients with Renal Impairment

In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m²), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

Geriatric Patients (Ages 65 Years and Over)

Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate < 70 mL/min/1.73 m²) is evident [see CLINICAL PHARMACOLOGY].

Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

Patients with Hepatic Disease

In hepatically impaired patients, topiramate plasma concentrations may be increased. The mechanism is not well understood.

Dosage Forms And Strengths

TOPAMAX® (topiramate) Tablets are available as debossed, coated, round tablets in the following strengths and colors:

25 mg cream (debossed “OMN” on one side; “25” on the other)
50 mg light-yellow (debossed “OMN” on one side; “50” on the other)
100 mg yellow (debossed “OMN” on one side; “100” on the other)
200 mg salmon (debossed “OMN” on one side; “200” on the other)

TOPAMAX® (topiramate capsules) Sprinkle Capsules contain small, white to off-white spheres. The gelatin capsules are white and clear.

They are marked as follows:

15 mg capsule with “TOP” and “15 mg” on the side
25 mg capsule with “TOP” and “25 mg” on the side

TOPAMAX® Tablets

TOPAMAX® (topiramate) Tablets are available as debossed, coated, round tablets in the following strengths and colors:

25 mg cream tablet (debossed “OMN” on one side; “25” on the other) and are available in bottles of 60 count with desiccant (NDC 50458-639-65)

50 mg light yellow tablet (debossed “OMN” on one side; “50” on the other) and are available in bottles of 60 count with desiccant (NDC 50458-640-65)

100 mg yellow tablet (debossed “OMN” on one side; “100” on the other) and are available in bottles of 60 count with desiccant (NDC 50458-641-65)

200 mg salmon tablet (debossed “OMN” on one side; “200” on the other) and are available in bottles of 60 count with desiccant (NDC 50458-642-65)

TOPAMAX® Sprinkle Capsules

TOPAMAX® (topiramate capsules) Sprinkle Capsules contain small, white to off-white spheres. The gelatin capsules are white and clear and are marked as follows:

15 mg capsule with “TOP” and “15 mg” on the side and are available in bottles of 60 (NDC 50458-647-65)

25 mg capsule with “TOP” and “25 mg” on the side and are available in bottles of 60 (NDC 50458-645-65)

Storage and Handling

TOPAMAX® Tablets should be stored in tightly-closed containers at controlled room temperature (59° to 86°F, 15° to 30°C). Protect from moisture.

TOPAMAX® Sprinkle Capsules should be stored in tightly-closed containers at or below 25°C (77°F). Protect from moisture.

Manufactured by: Janssen Ortho, LLC, Gurabo, Puerto Rico 00778. Manufactured for: Janssen Pharmaceuticals, Inc. Titusville, NJ 08560. Revised October 2012

Last reviewed on RxList: 11/9/2012
This monograph has been modified to include the generic and brand name in many instances.