Tiagabine dosing

Clearance of tiagabine may be reduced and thus plasma levels increased if taken with a non-enzyme inducing antiepileptic drug (e.g., valproate, gabapentin, lamotrigine), so tiagabine dose may need to be reduced... 

The efficacy and safety of tiagabine have been assessed in a study with an open screening phase (in which patients were titrated to the optimal tiagabine dose), followed by a double-blind, placebo-controlled, crossover phase (6). 

After an increase in tiagabine dose to 32 mg/day, a 28-year-old woman with partial epilepsy developed a prolonged and disoriented state associated with generalized spike-and-wave discharges on the electroencephalogram. Tiagabine was withdrawn and the status did not recur. 

All patients The following dosing recommendations apply to all patients taking tiagabine ... 

Dose titration Rapid escalation and/or large dose increments of tiagabine should not be used. 

Children (12 to 18 years of age) - Initiate tiagabine at 4 mg once/day. The total daily dose of tiagabine may be increased by 4 mg at the beginning of week 2. Thereafter, the total daily dose of may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or up to 32 mg/day. Give the total daily dose in 2 to 4 divided doses. Doses greater than 32 mg/day have been tolerated in a small number of adolescent patients for a relatively short... 

Typical Dosing Titration Regimen of Tiagabine for Patients Taking ElAEDs ... 

Absorption/Distribution - Tiagabine is nearly completely absorbed (more than 95%), with an absolute oral bioavailability of about 90%. Food slows the absorption rate but does not altering the extent of absorption. Absorption is rapid, with peak plasma concentrations occurring at approximately 45 minutes after an oral dose. Steady state is achieved within 2 days. 

Blood levels of tiagabine obtained depend on whether the patient also is receiving a drug that induces the metabolism of tiagabine. The presence of an inducer means that the attained blood level will be substantially reduced. Dosing should take the presence of concomitant medications into account. 

Generalized weakness Moderately severe to incapacitating generalized weakness has been reported following administration of tiagabine in approximately 1% of patients with epilepsy. The weakness resolved in all cases after a reduction in dose or discontinuation of tiagabine. 

Tiagabine is 90-100% bioavailable, has linear kinetics, and is highly protein-bound. The half-life is 5-8 hours and decreases in the presence of enzyme-inducing drugs. Food decreases the peak plasma concentration but not the area under the concentration curve (see Chapter 3). Hepatic impairment causes a slight decrease in clearance (and may necessitate a lower dose), but the drug does not cause inhibition or induction of hepatic... 

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. 

Clearance of tiagabine is increased if taken with an enzyme-inducing antiepileptic drug (e.g., carbamazepine, phenobarbital, phenytoin, primidone) and thus plasma levels are reduced however, no dose adjustments are necessary for treatment ot epilepsy as the dosing recommendations for epilepsy are based on adjunctive treatment with an enzyme-inducing antiepileptic drug... 

Although tiagabine is renally excreted, the pharmacokinetics of tiagabine in healthy patients and in those with impaired renal function are similar and no dose adjustment is recommended... 

Uldall P, Bulteau C, Pedersen SA, Dulac O, Lyby K. Tiagabine adjunctive therapy in children with refractory epilepsy a single-blind dose escalating study. Epilepsy Res 2000 42(2-3) 159-68. 

Uthman BM, Rowan AJ, Ahmann PA, Leppik IE, Schachter SC, SommerviUe KW, Shu V. Tiagabine for complex partial seizures a randomized, add-on, dose-response trial. Arch Neurol 1998 55(l) 56-62. 

Piccinelli P, Borgatti R, Perucca E, Tofani A, Donati G, Balottin U. Frontal nonconvulsive status epilepticus associated with high-dose tiagabine therapy in a child with familial bilateral perisylvian polymicrogyria. Epilepsia 2000 41(ll) 1485-8. 

Fitzek S, Hegemann S, Sauner D, Bonsch D, Fitzek C. Drug-induced nonconvulsive status epilepticus with low dose of tiagabine. Epileptic Disord 2001 3(3) 147-50. 

Tiagabine reaches peak serum concentration approximately 45 minutes following an oral dose in the fasting state. Pediatric patients reach peak concentration at approximately... 

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. " ... 

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