Monotherapy Epilepsy

TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate capsules) Sprinkle Capsules are indicated as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures.

Effectiveness was demonstrated in a controlled trial in patients with epilepsy who had no more than 2 seizures in the 3 months prior to enrollment. 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.

Adjunctive Therapy Epilepsy

TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate capsules) Sprinkle Capsules are indicated as adjunctive therapy for adults and pediatric patients ages 2-16 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.

Migraine

TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate capsules) Sprinkle Capsules are indicated for adults for the prophylaxis of migraine headache. The usefulness of TOPAMAX® in the acute treatment of migraine headache has not been studied.

Epilepsy

In the controlled add-on trials, no correlation has been demonstrated between trough plasma concentrations of topiramate and clinical efficacy. No evidence of tolerance has been demonstrated in humans. 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.

It is not necessary to monitor topiramate plasma concentrations to optimize TOPAMAX® 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

The recommended dose for topiramate monotherapy in adults and children 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 titrating according to the following schedule:

Adjunctive Therapy Use

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

The recommended total daily dose of TOPAMAX® as adjunctive therapy in adults with partial seizures is 200-400 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 - 50 mg/day followed by titration to an effective dose in increments of 25 - 50 mg/week. Titrating in increments of 25 mg/week may delay the time to reach an effective dose. Daily doses above 1,600mg have not beenstudied.

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, Adjunctive Therapy Controlled Trials in Patients With Primary Generalized Tonic-Clonic Seizures).

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

The recommended total daily dose of TOPAMAX® (topiramate) as adjunctive therapy for patients with partial 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 (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, Adjunctive Therapy Controlled Trials in Patients With Primary Generalized Tonic-Clonic Seizures).

Migraine

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

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

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/1.73m² ), 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 DOSAGE AND ADMINISTRATION: Patients with Renal Impairment and CLINICAL PHARMACOLOGY: Special Populations: Age, Gender, and Race).

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.

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

25 mg white (coded “TOP” on one side; “25” on the other)
50 mg light-yellow (coded “TOPAMAX” on one side; “50” on the other)
100 mg yellow (coded “TOPAMAX” on one side; “100” on the other)
200 mg salmon (coded “TOPAMAX” on one side; “200” on the other)

They are supplied as follows:

25 mg tablets - bottles of 60 count with desiccant (NDC 0045-0639-65)
50 mg tablets – bottles of 60 count with desiccant (NDC 0045-0640-65)
100 mg tablets – bottles of 60 count with desiccant (NDC 0045-0641-65)
200 mg tablets – bottles of 60 count with desiccant (NDC 0045-0642-65)

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

The capsules are supplied as follows:

15 mg capsules – bottles of 60 (NDC 0045-0647-65)
25 mg capsules – bottles of 60 (NDC 0045-0645-65)

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

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

TOPAMAX® (topiramate) and TOPAMAX® (topiramate capsules) are trademarks of Ortho-McNeil Neurologics, Inc.

ORTHO-McNEILNEUROLOGICS, INC.
Titusville, NJ 08560
10016700 © OMN 2005
Revised June 2005
FDA rev date: 10/19/2006

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