Tiagabine

Mechanism :

Tiagabine is a nipecotic acid derivative that is used as an adjunct in the treatment of partial seizures. The exact mechanism not known but in vitro experiments show that it increases the activity of gamma aminobutyric acid (GABA) by binding to the GABA uptake carrier, thus inhibiting the uptake of GABA into presynaptic neurons, resulting in an increased amount of GABA to be available to postsynaptic neurons.

Indication :

• Adjunct in refractory partial seizures.

Contraindications :

Discontinue treatment if there is sign of hypersensitivity. Hepatic impairment. Safety and efficacy have not been established in children <12 yr. Avoid abrupt withdrawal. Monitor for any sign/symptom (e.g. behaviour changes, anxiety, depression) of suicidal tendency or ideation. Pregnancy and lactation.

Dosing :

Adverse Effect :

CNS depression, dizziness, nervousness, somnolence. nausea, diarrhoea, abdominal pain, asthenia, tremor, weakness, chest pain, oedema, hypertension, palpitation, peripheral oedema, syncope, tachycardia, vasodilation.

Severe reactions: Toxic epidermal necrolysis and Stevens-Johnson syndrome.

Interaction :

Sedative Drugs or Ethanol: Increased sedation when used with other sedative drugs or ethanol.

Valproate: May increase free tiagabine levels.

CYP3A4 inhibitors: Concurrent use with CYP3A4 inhibitors (e.g. azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin and verapamil) may increase levels of tiagabine. CYP3A4 inducers (e.g. aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin and rifamycin) may decrease levels of tiagabine.

Renal Dose :

Hepatic Dose :