RESEARCH TRIANGLE PARK, NC, September 25, 2006 -- The Food and Drug Administration today approved a new use of the anti-seizure medicine Lamictal® (lamotrigine) Tablets for the treatment of one of the most serious forms of epilepsy -- Primary Generalized Tonic-Clonic (PGTC) seizures, also known as "grand mal" seizures. With this new indication, Lamictal can now be used as add-on therapy to treat PGTC seizures in children aged 2 and older as well as adults.
This new use marks the fifth FDA approval for Lamictal in epilepsy, making it one of the few antiepileptic drugs with established efficacy in a broad spectrum of seizure types, including partial and generalized seizures. Lamictal is also approved as maintenance therapy for adults with bipolar I disorder.
"Primary generalized tonic-clonic seizures represent one of the most serious forms of epilepsy and one in which additional effective treatments are needed," said Victor Biton, M.D., Director of the Arkansas Epilepsy Program, Little Rock, AR, a key investigator for the clinical study supporting this indication. "There are few treatments approved for generalized seizures and fewer approved for both PGTC and partial seizures. The approval of lamotrigine as add-on therapy for patients with PGTC seizures is a testament to the drug's broad spectrum of activity in the treatment of epilepsy."
PGTC seizures are the most common type of generalized seizures, occurring in approximately 20 percent of patients with epilepsy. These seizures usually occur without warning and are associated with wide-ranging physical and behavioral changes with potentially life-threatening complications. People who experience PGTC seizures become stiff, lose consciousness, and jerk repetitively. Patients may fall to the ground, bite their tongue, and lose bladder control. Serious injury, including broken bones, can occur. The seizure will typically last for a few minutes and then be followed by a period of drowsiness, confusion, headache, and sleep. For some people who have this type of seizure, it can take many hours to fully recover.
"PGTC seizures can be a scary and dangerous experience, especially for young children and their parents," said Edwin Trevathan, M.D., M.P.H., Director of the Division of Pediatric and Developmental Neurology at Washington University School of Medicine and Neurologist-in-Chief, St. Louis Children's Hospital, St. Louis, MO, another key investigator of the clinical study. "Since generalized seizures are more common in children than in adults, and since there have been very few new medications approved for use in primary generalized tonic-clonic seizures, this approval is particularly important."
ABOUT THE STUDY
FDA approval of Lamictal as add-on therapy in patients with PGTC seizures was based on a multicenter, placebo-controlled trial in pediatric (? age 2) and adult patients (n=117). Patients with partial seizures were excluded from this rigorous assessment of Lamictal. In the study, Lamictal was given to patients whose seizures were not well controlled, even while taking one or two other anti-seizure medications.
In this study, Lamictal was highly effective in reducing the frequency of PGTC seizures. Over the entire treatment period, Lamictal significantly reduced PGTC seizures by 66 percent compared to 34 percent for the placebo group (p=0.006). Similar effects were seen during the titration and maintenance phases of the study. Significantly more patients receiving Lamictal as maintenance therapy experienced at least a 50% reduction compared to placebo (72 % versus 49 %, p<0.05). Efficacy was similar across age groups.
Overall, Lamictal was associated with a favorable tolerability profile. The most common drug-related side effects observed in this clinical trial were dizziness (5% Lamictal, 2% placebo), drowsiness (5% Lamictal, 2% placebo), and nausea (5% Lamictal, 3% placebo). This study supports other findings establishing the efficacy and tolerability of Lamictal for a broad range of seizure types and patient ages.
Epilepsy is defined by recurrent unprovoked seizures characterized by a change in sensation, awareness, or behavior brought about by an electrical disturbance in the brain. The kind of seizure a person has depends on which part and how much of the brain is affected by the disturbance that produces seizures. Generalized seizures are seizures that involve the entire brain from the outset. In most cases, the cause of epilepsy is unknown. According to the Epilepsy Foundation, epilepsy affects about 2.7 million people in the United States of all ages.
Lamictal is indicated 1) as adjunctive therapy for partial seizures, primary generalized tonic-clonic seizures, and the generalized seizures of Lennox-Gastaut syndrome in adults and pediatric patients as young as 2 years and 2) for conversion to monotherapy in adults with partial seizures taking carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single AED.
Safety and effectiveness of Lamictal have not been established 1) as initial monotherapy, 2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate, 3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.
Lamictal is also approved for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adult patients treated for acute mood episodes with standard therapy. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established.
Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens Johnson syndrome, is approximately 0.8 percent (8 per 1000) in pediatric patients under the age of 16 years receiving Lamictal as adjunctive therapy for epilepsy, and 0.3 percent (3 per 1000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08 percent of adult patients who received Lamictal as initial monotherapy and 0.13 percent of adult patients who received Lamictal as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death.
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