Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiagabine (TGB) hydrochloride is a potential new antiepileptic drug (AED) undergoing clinical development. Experience in humans amounts to 1,810 patient-years of exposure. TGB was found to be tolerated in an integrated safety analysis of five double-blind, add-on therapy trials involving approximately 1,000 patients with epilepsy with difficult-to-control seizures with existing AEDs. Discontinuation resulting from adverse events were infrequent, occurring in 15% of patients receiving TGB compared to 5% receiving placebo. The most frequently reported adverse event was dizziness, which was usually transient and did not require medical intervention. Adverse events that were statistically significantly more common with TGB than placebo were dizziness, asthenia, nervousness, tremor, diarrhea, and depression (not major depression). Adverse events were usually mild to moderate in severity and transient, and most were associated with dose titration. The incidence, type, and severity of adverse events in long-term studies were comparable with those in short-term studies. Serious adverse events were uncommon and no idiosyncratic events were reported.
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PMID:Tiagabine: the safety landscape. 859 87

Tiagabine is a gamma-aminobutyric acid (GABA) uptake inhibitor which is structurally related to nipecotic acid but has an improved ability to cross the blood-brain barrier. Clinical trials have shown that tiagabine is effective as add-on therapy in the management of patients with refractory partial epilepsy. In short term studies of this indication, tiagabine < or = 64 mg/day for 7 to 12 weeks reduced the complex partial and simple partial seizure frequency by > or = 50% in 8 to 31 and 28.2 to 37% of patients, respectively. Tiagabine appeared to produce a sustained reduction in seizure frequency in studies of up to 12 months' duration. Data from preliminary studies are currently insufficient to confirm the usefulness of tiagabine when used as monotherapy or in the treatment of children with epilepsy. Further studies are, therefore, necessary to more fully elucidate the efficacy of the drug in these settings. Adverse events associated with tiagabine are primarily CNS-related and include dizziness, asthenia, nonspecific nervousness and tremor. Skin rash or psychosis occurred with similar frequencies among tiagabine- and placebo-treated patients. With long term administration (> or = 1 year for many patients), the profile and incidence of adverse events was similar to that for short term therapy. Tiagabine does not appear to affect the hepatic metabolism of other drugs such as carbamazepine and phenytoin. Possible disadvantages of tiagabine include its short plasma elimination half-life, necessitating 2 to 4 times daily administration, and its inducible hepatic metabolism. Thus, tiagabine is a new antiepileptic agent with a novel mechanism of action, which has demonstrated efficacy in the adjunctive treatment of patients with refractory partial epilepsy. Further investigation of the efficacy of tiagabine is expected to provide a clearer definition of its place in the treatment of epilepsy and its relative merits in relation to other antiepileptic drugs.
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PMID:Tiagabine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of epilepsy. 953 May 48

Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of gamma-aminobutyric acid (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain. The absorption and elimination of tiagabine follow linear pharmacokinetics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzyme-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral contraceptives. In the perforant pathway stimulation model of status epilepticus, tiagabine reduced the seizure number and severity, and also prevented the loss of pyramidal cells in the hippocampus as well as alleviated impairment of the spatial memory impairment associated with hippocampal damage. Tiagabine has both antiepileptogenic and anticonvulsant effects in the kindling model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has been also possible in substantial amount of patients with partial seizures in three trials. Tiagabine is generally well-tolerated. The most common adverse events in controlled studies involve the central nervous system; for example, dizziness, asthenia, nervousness, tremor, depressed mood and emotional lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagabine represents an important new therapeutic option for patients with treatment-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially emphasized since tiagabine has a low side-effect profile in the cognitive area.
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PMID:Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy. 1003 Apr 35

Tiagabine is a new antiepileptic drug which acts by blocking neuronal and glial GABA uptake and it is indicated in the treatment of partial epilepsies. Its pharmacokinetics is lineal, being extensively metabolized in the liver by means of CYP3A4 isoenzyme. Plasma elimination half life ranges between 5-8 hours in healthy volunteers, being markedly reduced when the drug is administered concomitantly with enzyme-inducing antinconvulsants. Tiagabine does not induce nor inhibit hepatic enzymes and, consequently, it does not modify the kinetics of simultaneously prescribed antiepileptic drugs. No relevant kinetic differences have been observed between adults and elderly subjects. Renal impairment does not alter the pharmacokinetic profile of tiagabine; hepatic disease, however, significantly reduces tiagabine elimination and lower daily doses of the drug are necessary in these patients. Although tiagabine elimination half life is short, it has been ascertained that therapeutic efficacy is similar when administered in 2 or 4 divided doses. Tiagabine is usually well tolerated; its most frequent side effects include dizziness, asthenia, nervousness, tremor, diarrhea and depressed mood.
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PMID:[Clinical implications of pharmacology and pharmacokinetics of tiagabine]. 1071 5

Tiagabine (TGB) is a novel antiepileptic drug efficacious for the treatment of partial epilepsies. The aim of that work is short presentation of current data concerning long-term safety of TGB. Tolerance to TGB does not develop with long-term therapy. Idiosyncratic reaction and changes in haematology and chemistry values have not been associated with TGB therapy. The most common adverse effects are dizziness, asthenia, nervousness, tremor, diarrhoea and depression. The current data do not show any evidence of relationship between visual field constriction and TGB treatment. No adverse effects on cognitive abilities have been found. There are contradictory data concerning tiagabine-induced nonconvulsive status epilepticus. Because of high safety and efficacy TBG is an important new antiepileptic drug for the treatment of intractable partial epilepsies.
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PMID:[Long-term safety of using tiagabine in epilepsy]. 1125 88

Tiagabine (TGB) is now registered in >20 countries, and the total number of treated patients approaches 90,000. Short-term safety data were derived mainly from five placebo-controlled, add-on studies in adults with therapy-resistant partial epilepsy, and two conversion to TGB monotherapy studies. Central nervous system (CNS)-related adverse effects, most frequently dizziness, were common with TGB treatment during the titration period; the risk became similar to placebo rates during fixed-dose periods. Other adverse events that were more frequent in TGB- than in placebo-treated patients were asthenia, nervousness, tremor, concentration difficulties, depressive mood, and language problems. TGB doses should be titrated slowly and taken with food to avoid rapid increases in plasma concentrations, thus minimizing the risks of adverse events. Overall, >2,500 patients have been exposed to TGB during clinical trials, with 1,274 patients treated >12 months, the majority of whom received TGB 24-60 mg/day. No idiosyncratic reactions have been linked to the use of TGB, and no abnormalities in hematology or common chemistry values were reported. In all the epilepsy studies combined, 21% of patients discontinued treatment because of adverse events, usually during the first 6 months of treatment. No adverse effects on cognitive abilities were detected when the neuropsychological effects of TGB add-on therapy and monotherapy were evaluated. TGB does not appear to cause an excess risk of psychosis or increase the incidence of status epilepticus or spike/wave discharges. No evidence of a relationship between visual field constriction and TGB treatment was found in a study of 15 patients converted to TGB monotherapy (mean dose, 22 mg/day; mean duration, 2.5 years) who had a full ophthalmologic evaluation. In conclusion, the characteristics of TGB in the management of partial epilepsy are enhanced by its favorable side-effect profile in the cognitive area.
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PMID:Long-term safety of tiagabine. 1152 Mar 23