indication

For the treatment of partial seizures

pharmacology

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.

toxicity

mptoms most often accompanying tiagabine overdose, alone or in combination with other drugs, have included: seizures including status epilepticus in patients with and without underlying seizure disorders, nonconvulsive status epilepticus, coma, ataxia, confusion, somnolence, drowsiness, impaired speech, agitation, lethargy, myoclonus, spike wave stupor, tremors, disorientation, vomiting, hostility, and temporary paralysis. Respiratory depression was seen in a number of patients, including children, in the context of seizures.

biotransformation

Tiagabine is likely metabolized primarily by the 3A isoform subfamily of hepatic cytochrome P450.

absorption

Tiagabine is nearly completely absorbed (>95%).

half life

7-9 hours

route of elimination

Approximately 2% of an oral dose of tiagabine is excreted unchanged, with 25% and 63% of the remaining dose excreted into the urine and feces, respectively, primarily as metabolites.

drug interactions

Amprenavir: The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Amprenavir is initiated, discontinued or dose changed.

Atazanavir: The strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Atazanavir is initiated, discontinued or dose changed.

Clarithromycin: The strong CYP3A4 inhibitor, Clarithromycin, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Clarithromycin is initiated, discontinued or dose changed.

Conivaptan: The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Conivaptan is initiated, discontinued or dose changed.

Darunavir: The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Darunavir is initiated, discontinued or dose changed.

Delavirdine: The strong CYP3A4 inhibitor, Delavirdine, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Delavirdine is initiated, discontinued or dose changed.

Fosamprenavir: The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Fosamprenavir is initiated, discontinued or dose changed.

Imatinib: The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Imatinib is initiated, discontinued or dose changed.

Indinavir: The strong CYP3A4 inhibitor, Indinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Indinavir is initiated, discontinued or dose changed.

Isoniazid: The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Isoniazid is initiated, discontinued or dose changed.

Itraconazole: The strong CYP3A4 inhibitor, Itraconazole, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Itraconazole is initiated, discontinued or dose changed.

Ketoconazole: The strong CYP3A4 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Ketoconazole is initiated, discontinued or dose changed.

Lopinavir: The strong CYP3A4 inhibitor, Lopinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Lopinavir is initiated, discontinued or dose changed.

Mefloquine: Mefloquine increases the risk of seizure and is contraindicated in persons with a history of convulsions. Possible reduction in the therapeutic effect of Tiagabine when used for other indications may also occur.

Miconazole: The strong CYP3A4 inhibitor, Miconazole, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Miconazole is initiated, discontinued or dose changed.

Nefazodone: The strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nefazodone is initiated, discontinued or dose changed.

Nelfinavir: The strong CYP3A4 inhibitor, Nelfinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nelfinavir is initiated, discontinued or dose changed.

Nicardipine: The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Nicardipine is initiated, discontinued or dose changed.

Posaconazole: The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Posaconazole is initiated, discontinued or dose changed.

Quinidine: The strong CYP3A4 inhibitor, Quinidine, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Quinidine is initiated, discontinued or dose changed.

Ritonavir: The strong CYP3A4 inhibitor, Ritonavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Ritonavir is initiated, discontinued or dose changed.

Saquinavir: The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Saquinavir is initiated, discontinued or dose changed.

Telithromycin: The strong CYP3A4 inhibitor, Telithromycin, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Telithromycin is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Tiagabine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tiagabine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tiagabine if voriconazole is initiated, discontinued or dose changed.