Gabitril (tiagabine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tiagabine, a nipecotic acid derivative, is an anticonvulsant.
Tiagabine, a nipecotic acid derivative, is an anticonvulsant agent. The drug is commercially available as the hydrochloride salt and differs structurally from other currently available anticonvulsant agents.
Although the precise mechanism of action of tiagabine is unknown, the drug enhances inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA). Tiagabine increases the amount of GABA available in extracellular spaces of the globus pallidus, ventral pallidum, and substantia nigra, suggesting a GABA-mediated anticonvulsant mechanism of action (i.e., inhibition of neural impulse propagations that contribute to seizures). Tiagabine inhibits presynaptic neuronal and glial GABA reuptake, and increases the amount of GABA available for postsynaptic receptor binding.
The drug does not stimulate GABA release, and does not have activity at other receptor binding and uptake sites at concentrations that inhibit the uptake of GABA. Tiagabine selectively blocks presynaptic GABA uptake by binding reversibly and saturably to recognition sites associated with GABA transporter protein in neuronal and glial membranes.
Tiagabine exhibits anticonvulsant activity in several animal seizure models. Although the drug is effective against tonic seizures induced in some animals by subcutaneous administration of pentylenetetrazole (PTZ), tiagabine is only partially effective against PTZ-induced clonic seizures in some animals, indicating that it may not have substantial activity against absence seizures in humans. Tiagabine decreases seizure severity and aftercharge duration in animals with amygdala-kindled seizures, indicating potential anticonvulsant activity against partial seizures in humans.
Tiagabine exhibits a dose-dependent effect against clonic seizures induced by proconvulsant methyl-6,7-dimethyoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), with diminished effectiveness at higher dosages, and is effective against audiogenic seizures in genetically epilepsy-prone animals. Tiagabine is partially effective against picrotoxin-induced seizures, bicuculline-induced seizures, and photic seizures, and is minimally effective against maximal electroshock seizures (MES) in animals.
Although tiagabine reduces the frequency of seizures in patients with epilepsy, use of the drug has been associated with a paradoxical occurrence of seizures in patients without a history of epilepsy.
In vitro binding studies indicate that tiagabine does not inhibit substantially the uptake of dopamine, norepinephrine, serotonin, glutamate, or choline, and does not bind substantially to dopamine D1 or D2; cholinergic muscarinic; serotonergic type 1A, type 2, or type 3 (5HT1A, 5HT2, or 5HT3, respectively); alpha1- or alpha2-adrenergic; beta1- or beta2-adrenergic; histamine H2 or H3; adenosine A1 or A2; opiate micro or kappa1; glutamate N-methyl-d-aspartate (NMDA); or GABAA receptors. Also, tiagabine has little or no affinity for sodium or calcium channels. Tiagabine binds to histamine H1, serotonergic type 1B (5HT1B), benzodiazepine, and chloride channel receptors at concentrations 20-400 times those that inhibit the uptake of GABA.
USES: Tiagabine is used to treat certain types of seizures (focal seizures). When tiagabine has been used for conditions other than seizures, serious reactions (including seizures in people who have never had them) have occurred. Talk to your doctor for more details.
Generic name: tiagabine HCl
Pronunciation: (tye-AG-a-been)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Gabitril
Indications
The following indications are listed for Gabitril:
- Partial Epilepsy Treatment Adjunct
Also known as: Partial Onset Seizures Treatment Adjunct, Partial Seizures Treatment Adjunct.
Dosing
No dosing information is available for this tab.
Tiagabine hydrochloride is administered orally with food. Food delays, but does not decrease the extent of tiagabine absorption. The initial tiagabine dosage is given once daily; following dosage increases after the initial period, the dosage should be administered in 2-4 divided doses daily.
Patients currently receiving or beginning therapy with tiagabine and/or any other anticonvulsant should be closely monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression. (See Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
The manufacturer states that a therapeutic range of plasma tiagabine concentrations has not been established; however, because of the potential for altered tiagabine clearance during concurrent administration of hepatic microsomal enzyme-inducing or -inhibiting drugs, it may be useful to determine plasma tiagabine concentrations before and after changes are made to the patient's drug regimen.
Because of the possibility of increasing seizure frequency, anticonvulsant drugs, including tiagabine, should not be discontinued abruptly. (See Discontinuance of Therapy under Warnings/Precautions: Warnings, in Cautions.)
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to tiagabine or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 5% or more of patients receiving tiagabine in combination with other anticonvulsant drugs and more frequently than with placebo in clinical trials include dizziness/lightheadedness, asthenia/lack of energy, somnolence, nausea, vomiting, diarrhea, nervousness/irritability, tremor, abdominal pain, generalized pain, insomnia, ataxia, confusion, rash, pharyngitis, and difficulty with concentration or attention.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of tiagabine in children younger than 12 years of age have not been established.
Pharmacokinetic analysis indicates that clearance and volume of distribution of tiagabine are similar in pediatric patients (3-10 years of age) and adults receiving concomitant enzyme-inducing anticonvulsant drugs; however, in the non-induced population (e.g., those receiving non-inducing anticonvulsants such as valproate), clearance is increased in pediatric patients compared with adults.
There are no adequate and well-controlled studies of tiagabine in pregnant women; adverse effects on embryofetal development, including teratogenic effects, have been observed in animals. Tiagabine should be used during pregnancy only if clearly indicated.
Women who are pregnant while receiving tiagabine should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 (for patients); registry information also is available on the website http://www.aedpregnancyregistry.org.
Tiagabine and/or its metabolites are distributed into milk in rats; it is not known whether the drug is distributed into human milk. The effects of tiagabine on the nursing infant also are unknown. Tiagabine should be used in nursing women only if the benefits clearly outweigh the risks.
Clinical trials have not included sufficient numbers of patients older than 65 years of age to determine whether they respond differently than younger patients; safety and efficacy of tiagabine in geriatric patients have not been established. However, the pharmacokinetic profile of tiagabine in healthy geriatric adults was similar to that in younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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