Short-term efficacy and safety of valproate sustained-release formulation in newly diagnosed partial epilepsy VIPe-study. A multicenter observational open-label study (original) (raw)
Related papers
2007
Objective: To evaluate the efficacy and safety of valproate (VPA) sustainedreleased in monotherapy across all ages in newly-diagnosed epileptic patients with partial seizures (PS) with or without secondary generalization. Methods: This was a multicenter, prospective, observational, open-label, noncomparative study involving the Gulf Cooperation Council (GCC) countries except the Kingdom of Saudi Arabia, and was performed between November 2004 and May 2006. Adults and children (6 years or older with newly diagnosed partial epilepsy [PE]) with or without secondary generalization were enrolled. The primary efficacy parameter was 6 month-remission rate (proportion of seizure-free patients in relation to total number of retained patients). Secondary efficacy parameters included: 6 month-retention rate, investigator’s clinical global impression rating, maximal effective dose and safety profile. Results: Seventy-seven patients were enrolled; 56% adults and 44% children, with average durati...
Journal of National Institute of Neurosciences Bangladesh, 2015
Background: Management of partial epilepsy is an important issue in the field of neurology. Objective: The purpose of the present study was to collect additional clinical data on efficacy and safety of sustained release sodium valproate chrono formulation as first-line monotherapy in patients newly or recently diagnosed with partial epilepsy in Bangladesh under daily practice condition. Methodology: This open-label, multicenter, non-controlled, prospective, observational study enrolled adults and children ? 6 years newly diagnosed with partial epilepsy with or without secondary generalization between March 2010 and February 2011. Patients were treated with sustained release sodium valproate. Primary evaluation criterion was the remission rate i.e. proportion of seizure-free patients at 6 months. Secondary evaluation criteria included retention rate at 6 months, remission rate at 1 and 3 months, investigator's global clinical impression rating, safety profile assessment. Results: A total of 185 adults and 115 children with mean 4.4 months duration of epilepsy were included. At inclusion the mean daily valproate dose in children was 329 mg and 568 mg in adults. The mean treatment duration in both children and adults was 5.5 months. At the end of 6 months 74.7% of the patients were seizure-free (children and adults; 79.1% vs 71.9%). The number of seizure free patients at 1 month was 109 (36.3%) and 175 (58.3%) at month 3. The treatment retention rate at 6 months was 87.3% with small higher trend in adults than children (88.6% vs. 85.2%). Among the patients 9.3% experienced side effects like drowsiness and weight gain. No severe adverse event was reported. Conclusion: Sodium valproate sustained release formulation is effective for the first-line treatment of partial epilepsy in both adults and children with acceptable tolerability. [
European Journal of Clinical Pharmacology, 2006
Conventional and sustained-release valproate in children with newly diagnosed epilepsy: a randomized and crossover study comparing clinical effects, patient preference and pharmacokinetics Abstract Objective: It has been suggested that sustainedrelease valproate (VPA) formulations may be more effective and better tolerated than conventional VPA due to better compliance and lower fluctuations in VPA serum concentrations, but comparative trials with conventional VPA in children are scarce. This randomized and crossover trial compared the efficacy (complete control of seizures), the tolerability, and the patient (or parents) preference of conventional VPA twice daily (CVbid) with those of sustained-release chrono VPA twice daily (ChVbid), once daily in the morning (ChVom) or once daily in the evening (ChVoe) in monotherapy. Methods: The study was carried out in 48 children (29 girls), aged 5-14 years, with newly diagnosed partial epilepsy (n=26), or idiopathic generalized epilepsy (n=22). The study duration was 16 months (four phases of 4 months each). VPA pharmacokinetics data were also compared in the different regimens. Mean VPA dosage was of approximately 870 mg/day (approximately 22 mg/kg/day) and mean VPA concentration was of approximately 89 mg/l at 12 h post-dose and of 54 mg/l at 24 h post-dose. Results: By intention in treatment there were no significant differences in efficacy (73%, 83%, 77% and 75%, respectively) or in adverse reaction frequency (56%, 58%, 67% and 46%, respectively). There were significant differences, however, in patient (or parents) preference, the order being ChVoe (31%) > ChVom (25%) > CVbid (17%) > ChVbid (8%). The mean VPA serum concentration fluctuation between 4 h and 0 h post-morning-dose was nonsignificantly lower after CVbid than after ChVbid. Fluctuation was significantly higher after ChVom than after CVbid or ChVbid. The mean VPA serum concentration difference between 12 h and 24 h post-dose was approximately 40 mg/l. Conclusion: Although our results should be confirmed by a larger study, they suggest that the efficacy and tolerability of chrono valproate is similar to that of conventional valproate, and that the main advantage is the once-daily administration.
Valproate in children with newly diagnosed idiopathic generalized epilepsy
Acta Neurologica Scandinavica, 2010
Objectives-Sparse information on dose-response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE.
Efficacy and safety of intravenous valproate for status epilepticus: a systematic review
2014
Introduction The effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE). Aim Our aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and safety of intravenous VPA for the treatment of SE. Methods Data sources included MEDLINE, back tracing of references in pertinent studies, and contact with the manufacturer of VPA (Sanofi-Aventis).
Epilepsy Research, 1992
We studied plasma levels and behavioural effects of a newly developed controlkxi release formulation of valproate (VPA-CR) in chitdren with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monothe~py of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher C,,,/C min ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.
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Amaç: Çok merkezli, çapraz geçiþli çalýþmanýn amacý parsiyel epilepsili hastalarda valproate etkinliðini ve kontrollü salýným formülasyonuyla (valproate-CR) uyumunun deðerlendirilmesidir. Hastalar ve Yöntemler: On merkezden 94 hasta çalýþmaya katýlmýþ ve %81,9u çalýþmayý tamamlamýþtýr. Klinik ve demografik özellikler baþlangýçta belirtilmiþtir, tedavi uyumu ve memnuniyeti, etkinlik ve advers olaylar dört vizitte deðerlendirilmiþtir. Nöbet sýklýðý, advers olaylarýn insidansý, tedavi uyumu ve hasta memnuniyeti, valproate-CRa geçiþi takiben tüm ölçümlerdeki anlamlý iyileþme ile iki tedavi süresi arasýnda anlamlý olarak fark mevcuttu. Bulgular: Ýlk vizitte hastalarýn %30,5inde ve beþinci vizitte %62,5inde ya nöbet olmadý ya da nöbetler seyrekleþti (p<0.001). Advers olaylar ikinci vizitte 35 (37.6%) iken, beþinci vizitte 19 (25%) hastada gözlenmiþtir. Tedavi uyumu ikinci vizitte %82,2 idi ve beþinci vizitte uzun etkili valproat forma geçiþten sonra oran %97,4e yükselmiþtir (p=0.001). Çalýþmanýn sonunda hastalarýn %84,9u tedaviden memnundu ve hastalarýn %74,4ü iyileþmiþti. Sonuç: Sonuç olarak valproate-CR kullanýmý yan etkilerin insidansýnýn düþüklüðü, hasta uyumu ve memnuniyetindeki iyileþme ile iliþkilidir.
Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children
Brain and Development, 2011
Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/ kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy.
Epilepsia, 2015
This document provides guidance on the use of valproate in women and girls from a joint task force of the Commission of European Affairs of the International League Against Epilepsy (CEA-ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in babies who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use valproate and treatment alternatives, the importance of seizure control and of patient and foetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: Where possible, valproate should be avoided in women of childbearing potential. The choi...