Tiagabine adverse effects

Tiagabine is indicated for the adjunctive treatment of partial seizures and is effective in doses ranging from 16 mg/d to 56 mg/d. Divided doses as often as four times per day are sometimes required. Some patients appear to do well with tiagabine monotherapy, which is generally well tolerated. Minor adverse events are dose-related and include nervousness, dizziness, tremor, difficulty in concentrating, and depression. Excessive confusion, somnolence, or ataxia may require discontinuation. Psychosis occurs rarely. Rash is an uncommon idiosyncratic adverse effect. Laboratory studies are usually normal. 

The rationale and use of modified-release formulations of antiepileptic drugs (carbamazepine, valproic acid, and tiagabine) have been reviewed (171). The authors concluded that modified-release formulations afford the advantages of better patient compliance, fewer adverse effects, and less fluctuation in plasma concentrations, making monitoring of drug concentrations easier. They concluded that these advantages should lead to better seizure control and improved quahty of life. 

Tiagabine is a nipecotic acid derivative which inhibits GABA re-uptake. It is highly bound to plasma proteins (96%) and is mainly eliminated by CYP3A-mediated oxidation, with a half-life of about 7 hours (1). It is used in add-on treatment of refractory partial seizures. Its adverse effects are mostly on the central nervous system. 

The use of tiagabine 4-16 mg/day in preventing migraine has been studied in 41 patients who had failed treatment with divalproex sodium because of adverse effects or lack of efficacy (4). There was at least a 50% reduction in the frequency of migraine headaches in 33 patients. There were adverse events in 12 patients, most commonly tiredness a few patients had weight gain or confusion. 

Hepatic dysfunction is associated with impaired tiagabine elimination and can result in greater susceptibility to adverse effects (SEDA-21, 75). Tiagabine should only be used cautiously and in reduced dosages in these patients. 

I Adverse Effects. The most frequently reported adverse effects of tiagabine are dizziness, asthenia, nervousness, tremor, diarrhea, and depression. Rash is uncommon with tiagabine. Adverse events usually are mild to moderate in severity and transient, and most were associated with dose titration. CNS side effects may be diminished by taking tiagabine with food, thus slowing the absorption rate. Serious adverse events were uncommon, and no idiosyncratic events, including visual field defects, were reported. " ... 

TOXICITY Adverse effects include dizziness, somnolence, and tremor, which are mild to moderate in severity and appear shortly after initiation of therapy. Tiagabine-enhanced effects of synapticaUy released GABA can facilitate spike-and-wave discharges in animal models of absence seizures, suggesting that tiagabine may be contraindicated in patients with generalized absence epilepsy patients with a history of spike-and-wave discharges have been reported to have exacerbations of their EEG abnormalities. 

Moderate social drinking does not appear to affect the serum levels of carbamazepine, ethosuximide or phenytoin. Some small changes are seen in the serum levels of phenobarbital and sodium valproate, but no changes in the control of epilepsy seem to occur. No pharmacokinetic interaction was detected between tiagabine and alcohol, and tiagabine did not alter the cognitive effect of alcohol. The adverse effects of both alcohol and antiepileptics, such as enhanced sedation, may be additive. 

Observational studies Almost 2000 patients have been recruited in an open prospective study in which tiagabine was added to a previous unsatisfactory antiepileptic treatment in patients with partial seizures [288 ]. At the second month of treatment, adverse effects were reported by 13% of patients and after 4 months by 8.6%. The most frequent were somno-lence/fatigue, headache/nausea, and anxiety/ mood disorders. No serious adverse events were reported. 

The effects of tiagabine have been studied in a 4-month, single-blind study in 52 children over the age of 2 years with different syndromes of refractory epilepsy (5). Adverse events, mostly mild to moderate, were reported by 39% of the children during the single-blind placebo period and by 83% of the children during tiagabine treatment. The events predominantly affected the nervous system weakness (19%), nervousness (19%), dizziness (17%), and somnolence (17%) were the most common. One child had hallucinations that responded to dosage reduction. Only three children withdrew because of adverse events. 

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