DOSAGE AND ADMINISTRATION
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:
| Morning Dose | Evening Dose |
| Week 1 | 25
mg | 25 mg |
| Week 2 | 50 mg | 50
mg |
| Week 3 | 75 mg | 75
mg |
| Week 4 | 100 mg | 100
mg |
| Week 5 | 150 mg | 150
mg |
| Week 6 | 200 mg | 200
mg |
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 1,600 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,
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:
| | Morning
Dose | Evening Dose |
| Week 1 | None | 25
mg |
| Week 2 | 25 mg | 25
mg |
| Week 3 | 25 mg | 50
mg |
| Week 4 | 50 mg | 50
mg |
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/1.73 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 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.
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Нумерология
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