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Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy).

Kluger G, Bauer B - Neuropsychiatr Dis Treat (2007)

Bottom Line: Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults.The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%).Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.

View Article: PubMed Central - PubMed

Affiliation: Klinik für Neuropädiatrie und Neurologische Rehabilitation, Epilepsiezentrum für Kinder und Jugendliche, Vogtareuth, Germany. gkluger@schoen-kliniken.de

ABSTRACT
Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change -42.5% vs +1.4% with placebo) and total seizures (-32.1% vs -11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.

No MeSH data available.


Related in: MedlinePlus

Median percentage reduction from baseline in total seizure frequency during 12-week double-blind and subsequent open-label rufinamide treatment (Glauser 2005a, 2005b; Eisai, data on file). Data shown separately for patients receiving rufinamide (n=74) or placebo (n=64) during double-blind treatment (Glauser 2005a), and combined for patients continuing in the extension study and receiving open-label rufinamide treatment (n=124) (Glauser 2005b).
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f1-ndt-3-3: Median percentage reduction from baseline in total seizure frequency during 12-week double-blind and subsequent open-label rufinamide treatment (Glauser 2005a, 2005b; Eisai, data on file). Data shown separately for patients receiving rufinamide (n=74) or placebo (n=64) during double-blind treatment (Glauser 2005a), and combined for patients continuing in the extension study and receiving open-label rufinamide treatment (n=124) (Glauser 2005b).

Mentions: Following completion of the double-blind study, 123 patients continued to receive open-label treatment in the extension phase, at a median dose of 1800 mg/day (range 103–4865 mg/day) for a median duration of 432 days (range 10–1149 days) (Glauser et al 2005b). The reduction in median total seizure frequency observed at 12 weeks was maintained, with some further improvement noted with continued treatment for up to 3 years (see Figure 1). Similarly, the responder rate for total seizures was maintained, with 36.9% of patients achieving a reduction in total seizures of at least 50% overall during the extension study. Furthermore, 21.3% of patients achieved a ≥75% reduction in total seizures overall during the extension study. There was no evidence for tolerance to rufinamide treatment.


Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy).

Kluger G, Bauer B - Neuropsychiatr Dis Treat (2007)

Median percentage reduction from baseline in total seizure frequency during 12-week double-blind and subsequent open-label rufinamide treatment (Glauser 2005a, 2005b; Eisai, data on file). Data shown separately for patients receiving rufinamide (n=74) or placebo (n=64) during double-blind treatment (Glauser 2005a), and combined for patients continuing in the extension study and receiving open-label rufinamide treatment (n=124) (Glauser 2005b).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654531&req=5

f1-ndt-3-3: Median percentage reduction from baseline in total seizure frequency during 12-week double-blind and subsequent open-label rufinamide treatment (Glauser 2005a, 2005b; Eisai, data on file). Data shown separately for patients receiving rufinamide (n=74) or placebo (n=64) during double-blind treatment (Glauser 2005a), and combined for patients continuing in the extension study and receiving open-label rufinamide treatment (n=124) (Glauser 2005b).
Mentions: Following completion of the double-blind study, 123 patients continued to receive open-label treatment in the extension phase, at a median dose of 1800 mg/day (range 103–4865 mg/day) for a median duration of 432 days (range 10–1149 days) (Glauser et al 2005b). The reduction in median total seizure frequency observed at 12 weeks was maintained, with some further improvement noted with continued treatment for up to 3 years (see Figure 1). Similarly, the responder rate for total seizures was maintained, with 36.9% of patients achieving a reduction in total seizures of at least 50% overall during the extension study. Furthermore, 21.3% of patients achieved a ≥75% reduction in total seizures overall during the extension study. There was no evidence for tolerance to rufinamide treatment.

Bottom Line: Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults.The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%).Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.

View Article: PubMed Central - PubMed

Affiliation: Klinik für Neuropädiatrie und Neurologische Rehabilitation, Epilepsiezentrum für Kinder und Jugendliche, Vogtareuth, Germany. gkluger@schoen-kliniken.de

ABSTRACT
Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change -42.5% vs +1.4% with placebo) and total seizures (-32.1% vs -11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.

No MeSH data available.


Related in: MedlinePlus