Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiagabine (TGB), a recently approved antiepileptic drug (AED), has a specific mechanism of action that is unique among AEDs. A potent AED with linear, predictable pharmacokineties, it inhibits gamma-aminobutyric acid (GABA) reuptake into neurons and glia. Tiagabine does not have any clinically relevant effects on hepatic metabolism or on serum concentrations of other AEDs, nor does it interact with commonly used non-AEDs. The most common side effects of TGB in controlled studies are dizziness, asthenia, somnolence, accidental injury, infection, headache, nausea, and nervousness. These events are usually mild to moderate in severity and generally do not require medical intervention. At dosages of 30-56 mg daily, TGB is an effective add-on treatment for partial seizures. Although patients who have medically refractory epilepsy can be converted to TGB monotherapy, more controlled studies are necessary to confirm the efficacy of TGB as monotherapy and to determine the effective dosage range.
 ...
PMID:A review of the antiepileptic drug tiagabine. 1062 90

The aim of this study was to determine the tolerability and efficacy of two oral regimens of levetiracetam, 1000 mg and 2000 mg twice daily, as add-on treatment without titration in patients with refractory epilepsy. After a 1- to 4-week baseline, 119 patients were randomized to receive levetiracetam 2000 mg daily, 4000 mg daily, or placebo for a 24-week double-blind period, then levetiracetam 4000 mg daily in a 24-week open-label phase. Somnolence was the most common reason for discontinuation, and along with asthenia, occurred more frequently with levetiracetam than placebo. Responder rates were higher with levetiracetam 2000 mg and 4000 mg daily (48.1% [P < 0.05] and 28.6% [NS], respectively) than placebo (16.1%). In the open-label phase, the overall responder rate was 43.0%. Switching from placebo to levetiracetam increased the overall responder rate from 16.7% to 44.0%. No such increase was observed with patients initiated on levetiracetam 2000 mg daily. Levetiracetam initiated at doses of 2000 mg or 4000 mg daily without titration is well-tolerated and effective as add-on therapy in patients with partial and/or generalized seizures. The higher dose may be related to an increased incidence of somnolence and is not necessarily more effective than the lower dose.
Seizure 2000 Mar
PMID:A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy. 1084 30

A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.
 ...
PMID:An assessment of levetiracetam as an anti-epileptic drug. 1106 Jul 65

The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.
 ...
PMID:Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy. 1107 81

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.
 ...
PMID:Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study. 1107 88

Tiagabine (TGB), a recently approved anti-epileptic drug (AED), has a specific and unique mechanism of action involving the inhibition of gamma-aminobutyric acid (GABA) re-uptake into neurones and glia. TGB is potent and has linear and predictable pharmacokinetics. It does not induce or inhibit hepatic metabolism and has no clinically significant effects on the serum concentrations of other AEDs or commonly used non-AEDs. Double-blind, placebo-controlled studies in primarily hepatic enzyme-induced patients showed that TGB 30 - 56 mg/day is an effective add-on treatment for all subtypes of partial seizures. The most common adverse effects in the trials were dizziness, asthenia (weakness), somnolence, accidental injury, infection, headache, nausea and nervousness. These side effects were usually mild to moderate in severity and generally did not require medical intervention. Long-term safety studies show continued efficacy of TGB over time and no evidence of tolerance for efficacy. Open studies confirm that patients with medically refractory partial epilepsy can be successfully converted to TGB monotherapy and that TGB may be effective for other seizure types, such as infantile spasms.
 ...
PMID:Pharmacology and clinical experience with tiagabine. 1133 78

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of levetiracetam are reviewed. Levetiracetam is an adjunctive treatment for partial-onset epileptic seizures. This drug inhibits seizure activity via a mechanism that does not involve excitatory or inhibitory neuronal pathways. Oral bioavailability is about 100%, and food does not alter absorption. Levetiracetam is minimally plasma protein bound (10%). Peak time to absorption after oral administration is one hour, and steady state is achieved in two days with twice-daily administration. Three clinical studies have demonstrated levetiracetam's ability to reduce seizure frequency in patients with partial-onset epilepsy. The most commonly reported adverse effects in clinical trials were somnolence, dizziness, infection, and asthenia. The potential for interactions with medications that are hepatically metabolized is minimal. The starting dosage is 500 mg twice a day; the maximum dosage is 3000 mg/day within four weeks. Levetiracetam is effective as an adjunctive treatment of partial-onset epilepsy with or without secondary generalization.
 ...
PMID:Levetiracetam. 1144 76

Tiagabine (TGB) is indicated as adjunctive therapy for partial seizures in adults and children aged 12 years and older. Double-blind, placebo-controlled studies of TGB treatment are under way in younger children with various forms of epilepsy. The results of pediatric pharmacokinetic trials indicate patterns similar to those seen in adults. An open-label study was conducted in the United States in 31 children with refractory complex partial seizures, with doses escalated every 2 weeks by 0.25 mg/kg up to a maximal daily dose of 1 mg/kg. Twenty-nine patients were treated with TGB for >1 year; 26 completed the study, of whom 18 were receiving monotherapy at study completion. A European dose-escalation study evaluated TGB (0.25-1.5 mg/kg/day) as add-on therapy in 52 children aged 2-15 years. TGB appeared to be more effective in localization-related epilepsy syndromes, with 17 of 23 patients with localization-related epilepsy having a 33% median reduction of seizure rate compared with baseline in the fourth month of treatment, and six patients having > or =50% seizure rate reduction. In this study, myoclonic seizures and spasms showed a poor response as opposed to encouraging findings reported by other groups with these seizure types. The adverse effect profile of TGB in children with epilepsy is similar to that in adults. In the U.S. study, most common adverse events were related to the central nervous system (CNS) and decreased over time. In the European study, mostly mild to moderate adverse events, including asthenia (19%), nervousness (19%), dizziness (17%), and somnolence (17%), were reported by 83% of TGB-treated children (39% of children reported adverse events during the single-blind placebo period). In summary, preliminary pediatric data with TGB suggest particular efficacy against epilepsy characterized by partial seizures or other syndromes, and further investigation is warranted.
 ...
PMID:Tiagabine (gabitril) experience in children. 1152 Mar 24

Levetiracetam is a new antiepileptic drug, structurally and mechanistically dissimilar to other marketed antiepileptic drugs. It is effective in reducing partial seizures in patients with epilepsy, both as adjunctive treatment and as monotherapy. Levetiracetam has many therapeutic advantages for patients with epilepsy. It has favorable pharmacokinetic characteristics (good bioavailability, linear pharmacokinetics, insignificant protein binding, lack of hepatic metabolism, and rapid achievement of steady-state concentrations) and a low potential for drug interactions. Recommended starting dosages are considered to be clinically effective; therefore, patients can have some protection from seizures soon after they begin levetiracetam. The most common adverse effects observed with levetiracetam are mild and include somnolence, asthenia, and dizziness. Clinical experience and data from meta-analyses indicate that levetiracetam is well tolerated, with efficacy comparable or slightly better than that observed with other new antiepileptic drugs. Levetiracetam may be particularly useful in patients who are unresponsive to other antiepileptic drugs, patients receiving drugs with increased potential for drug interactions, or those with hepatic impairment.
 ...
PMID:Levetiracetam: a novel antiepileptic drug. 1171 11

Second generation antiepileptics lamotrigine (LTG) and tiagabine (TGB) were primarily licensed for adjunctive treatment of simple and complex partial seizures with/without secondary generalisation as similarly effective drugs. Reduction of seizures frequency is the most important index of drug efficacy, but overall therapeutic benefit estimated as a quality of life is nowadays the target goal of management. In this study efficacy and tolerability of LTG or TGB as short-term add-on treatment in patients with refractory complex partial seizures were assessed by the use of both physician-rated measures (mean monthly seizure frequency, responders rate, adverse events, clinical biochemistry) and patients perceived change in their own quality of life estimation (descriptive scale and visual analogue scale-VAS). Comparable efficacy of LTG (n-22, 378 mg/day) and TGB (n-26, 43 mg/g) was assessed as 41 and 35% of responders and above half of patients with noticeable improvement. 25% of patients in both groups reported reduction of seizures severity in 4-points descriptive scale. Biochemistry values did not show clinically significant changes after treatment. 13% of patients on LTG reported adverse events (headache, asthenia, irritability, insomnia). This coefficient was greater for TGB-35% (asthenia, headache, sleepiness, vertigo). However, no case of discontinuation as a result of adverse events was reported for either of the tested drugs. Even if efficacy of LTG and TGB was comparable in objective measurements, only patients on LTG reported a significant quality of life improvement in VAS. This might be the consequence of more frequent adverse events and treatment schedule of TGB (triple dosing/day). This trial confirmed that VAS might be used as an easy additional test in evaluation of antiepileptic drug for individual patient in everyday clinical practice.
 ...
PMID:Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults. 1197 39


<< Previous 1 2 3 4 5 6 7 Next >>