Trade Names:Gabitril- Tablets 2 mg- Tablets 4 mg- Tablets 12 mg- Tablets 16 mg
Mechanism unknown; may block GABA uptake into presynaptic neurons, allowing more GABA to be available for binding with the GABA receptor of postsynaptic cells.
Tiagabine is rapidly and well absorbed, with food slowing absorption rate but not altering the extent of absorption. T max is 45 min following oral dosing in the fasting state. Bioavailability is 90%. Steady state is achieved within 2 days following multiple dosing.
Tiagabine is 96% bound to plasma proteins.
At least 2 metabolic pathways have been identified in humans: 1) thiophene ring oxidation leading to the formation of 5-oxo-tiagabine and 2) glucuronidation. Tiagabine is metabolized primarily by the 3A isoform subfamily of hepatic CYP-450 (CYP3A4), although contributions to the metabolism from CYP1A2, 2D6, or 2C19 have not been excluded.
The t ½ is 7 to 9 h in healthy volunteers, and 2 to 5 h in patients receiving hepatic enzyme-inducing drugs (eg, carbamazepine, phenytoin, primidone, phenobarbital). Approximately 2% of oral dose is excreted unchanged, with 25% and 63% of remaining dose excreted into the urine and feces, respectively.
Mean steady-state values were 40% lower in the evening than in the morning. Steady-state AUC values were 15% lower following the evening dose compared with AUC following the morning dose.
Moderate hepatic impairment (Child-Pugh class B) is caused by a 60% decrease in the Cl of unbound tiagabine. Patients with impaired liver function may require reduced initial and maintenance doses or longer dosing intervals.
Adjunctive therapy in treatment of partial seizures.
PO Initial dose: 4 mg once daily. Increase by 4 to 8 mg at wk intervals until clinical response achieved (max, 56 mg/day).Induced adolescents 12 to 18 yr of age
PO Initial dose: 4 mg once daily. Increase dose by 4 mg/day at beginning of wk 2. Thereafter, total daily dose may be increased by 4 to 8 mg at wk intervals until clinical response achieved (max, 32 mg/day).Non-induced adults and adolescents 12 to 18 yr of age
PO Following a given dose of tiagabine, the estimated plasma concentration is more than twice that in patients receiving enzyme-inducing agents. Tiagabine use in non-induced patients requires lower doses and slower titration.
Store at controlled room temperature (68° to 77°F). Protect from light and moisture.
Increased tiagabine Cl.Highly protein bound drugs
Because tiagabine is 96% protein bound, higher concentrations of tiagabine or the competing drug may occur.Valproate
Slight increases (about 10%) in valproate concentrations may occur.
None well documented.
Hypertension, palpitation, syncope, tachycardia, vasodilation (at least 1%).
Abnormal gait, asthenia, ataxia, attention/concentration difficulty, depression, dizziness, hostility, insomnia, nervousness, somnolence, tremor (at least 5%); agitation, confusion, decreased reflexes, depersonalization, dysarthria, emotional lability, euphoria, hallucinations, hyperkinesias, hypertonia, hypesthesia, hypotonia, language problems, malaise, memory difficulty, migraine, myoclonus, nystagmus, paranoid reaction, paresthesia, personality disorder, speech disorder, stupor, twitching, vertigo (at least 1%).
Alopecia, dry skin, pruritus, rash, sweating (at least 1%).
Amblyopia, pharyngitis, (at least 5%); abnormal vision, ear pain, epistaxis, otitis media, tinnitus (at least 1%).
Abdominal pain, diarrhea (at least 5%); increased appetite, gingivitis, mouth ulceration, nausea, stomatitis, vomiting (at least 1%).
UTI (at least 5%); dysmenorrhea, dysuria, metrorrhagia, urinary incontinence, vaginitis (at least 1%).
Ecchymosis (at least 5%); lymphadenopathy (at least 1%).
Myalgia (at least 5%); edema, peripheral edema, weight gain or loss (at least 1%).
Arthralgia, myasthenia, neck pain (at least 1%).
Bronchitis, dyspnea, increased cough, pneumonia (at least 1%).
Accidental injury, flu syndrome, infection, pain (at least 5%); allergic reactions, chest pain, chills, cyst (at least 1%).
Therapeutic tiagabine plasma levels have not been established. Because of potential for pharmacokinetic interactions between tiagabine and drugs that induce or inhibit hepatic metabolizing enzymes, it may be useful to obtain plasma levels of tiagabine before and after changes are made in the therapeutic regimen.
Category C .
Safety and efficacy in children younger than 12 yr of age not established.
Dosage reduction or longer dosing interval may be necessary.
May cause dizziness, somnolence, and other symptoms and signs of CNS depression.
Impaired concentration, speech or language problems, confusion, somnolence, and fatigue can occur. Some of these reactions were dose related and usually began during initial titration. In addition, some patients with a history of spike and wave discharges on EEG may have exacerbations of EEG abnormalities associated with cognitive/neuropsychiatric reactions, which may be a manifestation of underlying seizure activity. Dosage reduction of tiagabine may be necessary.
Moderately severe to incapacitating generalized weakness has been reported following administration of tiagabine. Weakness resolved in all cases after the dose was reduced or therapy was discontinued.
Tiagabine may bind to melanin-containing tissues. Long-term use may cause toxicity and ophthalmologic changes.
Tiagabine use has been associated with new onset seizures and status epilepticus in patients without epilepsy. Discontinue use in nonepileptic patient who develops seizures and evaluate patient for underlying seizure disorder.
During clinical trials, some patients experienced status epilepticus, and 10 sudden unexpected deaths occurred. Evidence suggested that this reflected population rates and was not caused by tiagabine.
Use of tiagabine in non-induced patients requires lower doses and slower dosage titration.
Do not discontinue anti-epileptic drugs abruptly because of possible increased seizure frequency upon drug withdrawal.
Agitation, ataxia, confusion, depression, drowsiness, hostility, impaired consciousness, lethargy, myoclonus, somnolence, speech difficulty, weakness.
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