Brands, Medical Use, Clinical Data
- Neuroprotective Agents
Brands / Synonyms
Gabitril; Tiagabina [Inn-Spanish]; Tiagabine [Inn]; Tiagabinum [Inn-Latin]
For the treatment of partial seizures
Tiagabine is used primarily as an anticonvulsant for the adjunctive treatment of epilepsy. The precise mechanism by which Tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells.
Mechanism of Action
Though the exact mechanism by which Tiagabine exerts its effect on the human body is unknown, it does appear to operate as a selective GABA reuptake inhibitor.
Tiagabine is nearly completely absorbed (>95%).
Biotrnasformation / Drug Metabolism
Tiagabine is likely metabolized primarily by the 3A isoform subfamily of hepatic cytochrome P450..
GABITRIL is contraindicated in patients who have demonstrated hypersensitivity to the drug or its
In evaluating the potential for interactions among co-administered antiepilepsy drugs (AEDs), whether
or not an AED induces or does not induce metabolic enzymes is an important consideration. Phenytoin, phenobarbital
and carbamazepine are ge nerally classified as enzyme inducers; valproate and gabapentin are not. GABITRIL is
considered to be a non-enzyme inducing AED.
The drug interaction data described in this section were obtained from studies involving either
healthy subjects or patients with epilepsy.
Effects of GABITRIL on other Antiepilepsy Drugs (AEDs) :
Phenytoin: Tiagabine had no effect on the steady-state plasma concentrations of phenytoin in patients
Carbamazepine: Tiagabine had no effect on the steady-state plasma concentrations of
carbamazepine or its epoxide metabolite in patients with epilepsy.
Valproate: Tiagabine causes a slight decrease (about 10%) in steady-state valproate
Phenobarbital or Primidone : No formal pharmacokinetic studies have been performed
examining the addition of tiagabine to regimens containing phenobarbital or primidone. The addition of tiagabine in a
limited number of patients in three well-controlled studies caused no systematic changes in phenobarbital or
primidone concentrations when compared to placebo.
Effects of other Antiepilepsy Drugs (AEDs) on GABITRIL :
Carbamazepine: Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in
patients taking carbamazepine with or without other enzyme- inducing AEDs.
Phenytoin: Population pharmacokinetic analyses indicate that tiagabine clearance is 60%
greater in patients taking phenytoin with or without other enzyme- inducing AEDs.
Phenobarbital (Primidone): Population pharmacokinetic analyses indicate that tiagabine
clearance is 60% greater in patients taking phenobarbital (primidone) with or without other enzyme-inducing AEDs.
Valproate: The addition of tiagabine to patients taking valproate chronically had no
effect on tiagabine pharmacokinetics, but valproate significantly decreased tiagabine binding in vitro from
96.3 to 94.8%, which resulted in an increase of approximately 40% in the free tiagabine concentration. The clinical
relevance of this in vitro finding is unknown.
Interaction of GABITRIL with Other Drugs :
Cimetidine : Co-administration of cimetidine (800 mg/day) to patients taking tiagabine chronically had
no effect on tiagabine pharmacokinetics.
Theophylline: A single 10 mg dose of tiagabine did not affect the pharmacokinetics of
theophylline at steady state.
Warfarin: No significant differences were observed in the steady-state pharmacokinetics
of R-warfarin or S-warfarin with the addition of tiagabine given as a single dose. Prothrombin times were not
affected by tiagabine.
Digoxin: Concomitant administration of tiagabine did not affect the steady-state
pharmacokinetics of digoxin or the mean daily trough serum level of digoxin.
Ethanol or Triazolam: No significant differences were observed in the pharmacokinetics
of triazolam (0.125 mg) and tiagabine (10 mg) when given together as a single dose. The pharmacokinetics of ethanol
were not affected by multiple-dose administration of tiagabine. Tiagabine has shown no clinically important
potentiation of the pharmacodynamic effects of triazo lam or alcohol. Because of the possible additive effects of
drugs that may depress the nervous system, ethanol or triazolam should be used cautiously in combination with
Oral Contraceptives: Multiple dose administration of tiagabine (8 mg/day monotherapy)
did not alter the pharmacokinetics of oral contraceptives in healthy women of childbearing age.
Antipyrine : Antipyrine pharmacokinetics were not significantly different before and
after tiagabine multiple-dose regimens. This indicates that tiagabine does not cause induction or inhibition of the
hepatic microsomal enzyme systems responsible for the metabolism of antipyrine.
Interaction of GABITRIL with Highly Protein Bound Drugs:
In vitro data showed that tiagabine is 96% bound to human plasma protein and therefore has the potential to
interact with other highly protein bound compounds. Such an interaction can potentially lead to higher free fractions
of either tiagabine or the competing drug.