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FDA Approves New Indication for Topamax (Topiramate) as Initial Monotherapy for Adults and Children with Epilepsy

TITUSVILLE, NJ -- June 30, 2005 -- The U.S. Food and Drug Administration (FDA) yesterday approved a new use for Topamax® (topiramate) Tablets and Sprinkle Capsules 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 two seizures in the three 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.

"Anti-epilepsy medications, or neuromodulators, are selected based on seizure type; however, the specific seizure type may not always be obvious at the time of diagnosis," said Tracy Glauser, MD, director of the Comprehensive Epilepsy Center at the Cincinnati Children's Hospital. "A treatment like Topamax, which provides coverage for both partial-onset and primarily generalized tonic-clonic seizures, offers doctors an option in situations where differentiating between these seizure types is difficult."

Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain that temporarily disrupt normal brain function. Seizures are classified as "generalized," originating in both sides of the brain simultaneously, or "partial-onset," starting in one area of the brain.

In a double-blind clinical trial, 470 patients with partial-onset or primary generalized tonic-clonic seizures were randomized to treatment with 50 mg or 400 mg/day of Topamax. The primary efficacy assessment was a group comparison of time to first seizure during the double-blind phase of the study. Comparison of the Kaplan-Meier survival curves of time to first seizure favored the 400 mg/day group over the 50 mg/day group.

The recommended dose for monotherapy in patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58 percent 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.

"We are extremely pleased with the monotherapy approval for Topamax," said Gregory L. Barkley, MD, chair of the Epilepsy Foundation's professional advisory board. "This approval provides doctors with another important treatment option for their patients with epilepsy."

Epilepsy is one of the most common neurological disorders, occurring in an estimated 2.7 million Americans. Each year in the United States, approximately 200,000 people are diagnosed with epilepsy for the first time.

Important Safety Information
As monotherapy, the most common side effects of Topamax (in the 400 mg/day group and at a rate higher than the 50 mg/day group) in adults were: paresthesia, weight decrease, somnolence, anorexia, dizziness, and difficulty with memory; and in children: weight decrease, upper respiratory tract infection, paresthesia, anorexia, diarrhea, and mood problems.

In addition, Topamax has been associated with serious adverse events including: hyperchloremic, non-anion gap metabolic acidosis (lowering of serum bicarbonate levels) -- measurement of baseline and periodic serum bicarbonate levels is recommended; acute myopia and secondary angle closure glaucoma -- patients should seek medical attention if they experience blurred vision or ocular pain; oligohidrosis and hyperthermia -- occurs most often in hot weather and in children; cognitive/psychiatric side effects, including somnolence and fatigue, cognitive dysfunction, and psychiatric/behavioral disturbances; hyperammonemia with or without encephalopathy -- associated with the concomitant use of valproic acid; and kidney stones-patients should maintain an adequate fluid intake to minimize the risk of renal stone formation.

In women taking combination oral contraceptives with Topamax, a significant decrease in estrogen exposure has been shown at Topamax doses greater than or equal to 200 mg/day. The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered.

To date, Topamax has been used to treat more than 4 million patients worldwide. Currently, Topamax is approved for use as a first-line treatment for epilepsy in more than 65 countries around the world.


SOURCE: Ortho-McNeil Neurologics, Inc.

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