Proven Safety & Efficacy

Consider TOPAMAX

  • Indicated for initial monotherapy in adults and children for partial-onset and primary generalized tonic-clonic seizures1
  • The AAN/AES guidelines support TOPAMAX, with the broadest class I evidence, as an effective treatment for a broad range of seizure types in adults and children2
  • Lower potential for drug-drug interactions3,4
    • Low protein binding1,3
    • Low potential for P450 enzyme induction1,5
  • Not associated with drug-induced weight gain1
  • More than 4 million patients worldwide have been treated with topiramate*6
  • Indicated as adjunctive therapy in adults and children for primary generalized tonic-clonic seizures, partial-onset seizures or seizures associated with Lennox-Gastaut Syndrome1

*Since 1995, regardless of condition.

TOPAMAX: Documented Broad Coverage of Seizure Types

TOPAMAX is 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.

TOPAMAX is indicated as adjunctive therapy in patients 2 years of age and older with primary generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome.

Compare FDA-Approved Indications9

Broad Spectrum Efficacy Chart
  • * Comparative product information obtained from the 2006 Physicians’ Desk Reference® and individual product Web sites as of February 5, 2007.9
  • † Divalproex sodium is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Divalproex sodium is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.
  • ‡ Indicated for conversion to monotherapy in adults with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single AED.

Proven efficacy across seizure types in adults and children

Monotherapy: proven efficacy in partial-onset and primary generalized
tonic-clonic seizures

Study design10

  • Multinational, randomized, double-blind, parallel-group dose-comparison trial:
    • 487 adults and children (6 to 83 years of age) diagnosed with epilepsy
    • Patients could have only 1 or 2 partial-onset or generalized tonic-clonic seizures within a
      3-month retrospective baseline period
    • 49% of patients had no prior AED treatment
  • 470 were titrated to TOPAMAX 50 mg/day or 400 mg/day:
    • Instead of placebo, the low-dose arm received 50 mg/day
  • In the 400 mg/day group (higher-dose arm):
    • Minimum study inclusion dose was 150 mg/day
    • Dosage was adjusted for tolerability
  • Primary efficacy endpoint was the comparison of time to first seizure between 400 mg/day and 50 mg/day

Study results10

  • Kaplan-Meier survival analyses for time to first seizure (n=470) favored the 400 mg/day arm over the 50 mg/day arm (P=0.0002)
  • First statistically significant difference in terms of seizure protection was seen at day 14 when patients were receiving either 100 mg/day or 25 mg/day
  • Seizure-free rates at 12 months were 76% and 59%, respectively 
  • Differences favoring the higher-dose arm were significant in patients with partial-onset seizures (P=0.009) and in those with primary generalized tonic-clonic seizures (P=0.005)
  • 58% of patients were maintained on the target dose of 400 mg/day
  • The mean dose achieved in the 400 mg/day arm was 275 mg/day1

Kaplan-Meier estimates of cumulative rates for time to first seizure10

First Seizure Chart
  • *At day 14, P=0.05
Lgs Chart

Adjunctive therapy: proven efficacy in partial-onset and primary generalized tonic-clonic seizures

In controlled clinical trials, TOPAMAX has been effective in reducing monthly seizure rates by at least 50% in approximately 57% of patients with primary generalized tonic-clonic seizures.6,11,12

6,14 Pgts Chart

An analysis of a study in adults with partial-onset seizures indicates that patients may notice a beneficial effect on seizures early—as early as 2 weeks. After 16 weeks of TOPAMAX therapy, 44% of adults with partial-onset seizures had their monthly seizure rate reduced by at least 50%.6,14

6, 14 Posa Chart

After 16 weeks of TOPAMAX therapy, 39% of children with partial-onset seizures achieved a
≥ 50% reduction in their monthly seizure rate.13

13 Posc Chart

In their monthly rate of drop attack seizures, 28% of patients with Lennox-Gastaut syndrome achieved a 50% or greater reduction in seizure frequency from baseline with TOPAMAX.6,15

6,15 Lgs Chart

Please see full US Prescribing Information.

AAn/AES Guidelines

Topiramate is recommended for use by the AAN/AES for initial monotherapy in partial-onset and primary generalized tonic-clonic seizures.

  • The guidelines support TOPAMAX, with the broadest class l evidence, as an effective treatment for a broad range of seizure types in adults and children2
2 AAN 1 Chart
  • *Received US Food and Drug Administration (FDA) approval for this indication after publication of this study.
  • †Not FDA-approved for this indication at the time of publication.

Level A
Established as effective, ineffective, or harmful for the given condition in the specified population. Requires at least one convincing class I study or at least two consistent class II studies.

Level B
Probably effective, ineffective, or harmful for the given condition in the specified population. Requires at least one convincing class II study or at least three consistent class III studies.

TOPAMAX Is Generally Well Tolerated In Adults And Children as Initial Monotherapy

TOPAMAX has extensive clinical experience in treating different seizure types and patient populations.

  • More than 4 million patients worldwide have been treated with topiramate6*
  • TOPAMAX has a linear dose-plasma concentration relationship, minimal enzymatic autoinduction, and lower potential for drug interaction. It is not necessary to monitor topiramate plasma concentrations to optimize TOPAMAX therapy
  • TOPAMAX has low protein binding and is primarily renally cleared5
  • TOPAMAX and combination oral contraceptives†
    • No significant effect on either progestin or ethinyl estradiol (EE) levels for TOPAMAX doses of 50 mg/day to 200 mg/day
    • TOPAMAX doses of 200 mg/day to 800 mg/day were associated with a decrease in EE levels
    • The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptives with TOPAMAX. Patients should report any change in bleeding patterns.
  • TOPAMAX is not associated with drug-induced weight gain.

* Since 1995, regardless of condition.
† Based on pharmacokinetic data with an oral contraceptive product containing norethindrone 1mg and ethinyl estradiol 35 μg.

TOPAMAX Is Generally Well Tolerated In Adults And Children as Initial Monotherapy

The most frequently reported adverse events in adults taking TOPAMAX as initial monotherapy at a dosage of 400 mg/day were paresthesia, weight decrease, somnolence, anorexia, dizziness, and difficulty with memory (not otherwise specified).1

The majority of cognitive-related events were mild to moderate in severity.1

TOPAMAX is also generally well tolerated in children. The most commonly reported adverse events observed in the higher-dose arm in clinical trials with TOPAMAX monotherapy are shown below.1

GWT 1 1 Chart
GWT 1 2 Chart
  • *Cumulative incidence of treatment-emergent adverse events where rate was ≥ 10%
  • The incidence of cognitive-related events in children was generally lower than those observed in adults1
  • The rate of withdrawal due to adverse events in the higher-dose arm was 21% in adults and 12% in children1
  • More than 4 million patients worldwide have been treated with topiramate6†

†Since 1995, regardless of condition.

TOPAMAX Is Generally Well-Tolerated at 200 mg/day as Add-On Therapy

A double-blind, placebo-controlled study evaluated a low dose of TOPAMAX as add-on therapy at 200 mg/day in adults with treatment resistant partial-onset seizures. The results proved that TOPAMAX 200 mg/day is an appropriate initial target dose. There was a low incidence of adverse events and only 8% of TOPAMAX-treated patients discontinued therapy due to adverse events.12

12‡ GWT2 Chart
  • ‡ Adverse events more frequent in TOPAMAX-treated patients with reported incidence >5%. Patients in these add-on trials were receiving 1 to 2 concomitant AEDs in addition to TOPAMAX or placebo.
  • TOPAMAX [Prescribing Information]. Titusville, NJ: Ortho-McNeil Neurologics®; 2006.
  • French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new onset epilepsy patients. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62:1252-1260.
  • Bourgeois BFD. Pharmacokinetics and pharmacodynamics of antiepileptic drugs. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:655-664.
  • Kyllonen KC, Gupta A. Selected drug interactions between antiepileptic drugs and other types of medications. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 4th ed. Philadelphia: Lippincott Williams & Wilkins;2006:665-669.
  • Nallani SC, Glauser TA, Hariparsad N, et al. Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia. 2003;44:1521-1528.
  • Data on file, Ortho-McNeil Neurologics®
  • Baram TZ, Hartman AL, Vining EPG, et al. Seizures. In: Johnson RT, Griffin JW, McArthur JC, eds. Current Therapy in Neurologic Disease. 7th ed. Philadelphia: Mosby;2006:23-53.
  • Tomson T. Drug selection for the newly diagnosed patient: when is a new generation antiepileptic drug indicated? J Neurol. 2004 Sep;251:1043-1049.
  • Physician's Desk Reference Web site.  Available at: www.pdr.net.  Accessed February 5, 2007.
  • Arroyo S, Dodson WE, Privitera MD, et al, for the EPMN-106/INT-28 Investigators. Randomized dose-controlled study of topiramate as first-line therapy in epilepsy. Acta Neurol Scand. 2005;112:214-222.
  • Biton V, Montouris GD, Ritter F, et al, and the Topiramate YTC Study Group. A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Neurology. 1999;52:1330-1337.
  • Guberman A, Neto W, Gassmann-Mayer C, and the EPAJ-119 Study Group. Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurol Scand. 2002;106:183-189.
  • Elterman RD, Glauser TA, Wyllie E, et al, and the Topirmate YP Study Group. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Neurology. 1999;52:1338-1344.
  • Faught E, Wilder BJ, Ramsay RE, et al, and the Topiramate YD Study Group. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Neurology. 1996;46:1684-1690.
  • Sachdeo RC, Glauser TA, Ritter F, et al, and the Topiramate YL Study Group. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology. 1999;52:1882-1887.
  • Doose DR, Wang S-S, Padmanabhan M, Schwabe S, Jacobs D, Bialer M. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia. 2003;44:540-549.
  • Rogawski MA, Loscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004;5:553-5647.