Tiagabine.

Abstract

Tiagabine inhibits gamma-aminobutyric acid uptake into neurons and glia. This mechanism of action is specific and unique among the antiepileptic drugs (AEDs). Tiagabine is efficacious in animal seizure models at subtoxic doses. There is no evidence of clinically important teratogenicity, carcinogenicity or mutagenicity in animals treated acutely or chronically with tiagabine. Tiagabine has no clinically relevant effect on hepatic metabolism or serum levels of other AEDs, has no clinically significant effects on laboratory values and has not been shown to have any clinically important interactions with common non-AEDs. Tiagabine has linear, predictable pharmacokinetics that do not vary significantly with age. Adverse effects are usually mild to moderate in severity and almost always resolve without medical intervention. The most common adverse events in controlled studies are dizziness, asthenia, somnolence, accidental injury, infection, headache, nausea and nervousness. Tiagabine is effective as add-on therapy for partial seizures in patients with medically refractory epilepsy in doses ranging from 32-56 mg daily. Despite its short half-life of 2-3 hours in patients on enzyme-inducing AEDs, tiagabine is effective when dosed 2-3 times a day. Conversion to tiagabine monotherapy can be achieved in patients with medically refractory epilepsy, though additional studies are needed to establish the effective dosage range. The introduction of drugs like tiagabine that have known mechanisms of action which differ from existing treatments further increases the range of options for patients with epilepsy.