GABITRIL

What it is

GABITRIL is an antiepileptic drug. The active ingredient is tiagabine, present as tiagabine hydrochloride monohydrate. Tiagabine is a potent and selective inhibitor of both neuronal and glial GABA (γ-amino-butyric acid) uptake, resulting in an increase in GABAergic mediated inhibition in the brain. GABITRIL is available as 5 mg, 10 mg and 15 mg white film-coated tablets.

Approved indications

— Treatment of partial seizures, as add-on therapy in patients who are not controlled satisfactorily with other antiepileptic drug(s).

Dosing overview

GABITRIL should be taken with meals in three daily doses. The initial dosage is 7.5–15 mg daily, followed by weekly increments of 5–15 mg daily. The usual maintenance dose is in the range of 30–50 mg daily. Doses up to 70 mg daily have been well tolerated. In patients who are not taking enzyme-inducing drugs, the maintenance dose should initially be 15–30 mg/day. Safety and effectiveness in children below the age of 12 years have not been established. Therefore, the drug should not be used in children under 12 years.

Key safety warnings

It is important to follow the recommended rate of dosage titration with GABITRIL in order to minimise the potential for adverse events. The dose should be carefully titrated to reduce the risk of paradoxical seizure-like activity. Non-convulsive status epilepticus (paradoxical) has been reported with tiagabine in a relatively-resistant population requiring add-on therapy, particularly during dose titration. In patients with a history of serious behavioural problems including generalised anxiety and depression, there is a risk of recurrence of these symptoms during GABITRIL treatment. Treatment with GABITRIL should therefore be initiated with low doses and patients observed carefully. Rare cases of visual field defects have been reported with tiagabine. If visual symptoms develop, or if a field defect is suspected, the patient should be referred to an ophthalmologist for further evaluation including perimetry. Spontaneous bruising has been reported. If such bruising is observed, full blood count, including platelets, should be performed. Serious rash, including vesiculobullous rash has occurred in patients receiving GABITRIL. Post-marketing reports have shown that GABITRIL has been associated with new onset seizures and status epilepticus in patients without epilepsy. Dose may be an important predisposing factor in the development of seizures, although seizures have been reported in patients taking doses as low as 4 mg/day. In most cases, patients were using concomitant medications (antidepressants, antipsychotics, stimulants, opioids) that are thought to lower the seizure threshold. Antiepileptic drugs, including tiagabine hydrochloride monohydrate, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour.

Contraindications

GABITRIL should not be used in case of known hypersensitivity to tiagabine or any of the tablet components, severely impaired liver function, or combination with St John Wort (hypericum perforatum).

PBS listing

GABITRIL tablets are listed on the PBS as 5 mg, 10 mg and 15 mg strengths with streamlined restriction. Ex-manufacturer prices are A$22.73 (5 mg), A$45.47 (10 mg) and A$65.40 (15 mg).

Regulatory history

GABITRIL was first listed on the ARTG on 14 September 2006, with registrations for 5 mg, 10 mg and 15 mg tablets.