LEVERIUOL

What it is

Leveriuol is a medicine containing levetiracetam, available as film-coated tablets in strengths of 250 mg, 500 mg, 1000 mg and 750 mg. The tablets are intended for oral administration and must be swallowed with liquid.

Approved indications —

Treatment of partial onset seizures with or without secondary generalisation in epileptic patients aged 4 years and older, initially as add-on therapy. — Monotherapy in the treatment of partial onset seizures, with or without secondary generalisation, in patients from 16 years of age with newly diagnosed epilepsy. — Add-on therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy. — Add-on therapy in the treatment of primary generalised tonic-clonic seizures in adults and children from 4 years of age with idiopathic generalised epilepsy.

Dosing overview

The daily dose is administered in two equally divided doses. Dosing varies by indication and patient characteristics. For monotherapy in adults: the recommended starting dose is 250 mg twice daily, increased to 500 mg twice daily after two weeks, with further increases possible by 250 mg twice daily every two weeks depending on clinical response; the maximum dose is 1,500 mg twice daily. For add-on therapy in adults and adolescents aged 12 to 17 years weighing 50 kg or more: the therapeutic dose is 500 mg twice daily, which can be started on the first day of treatment; depending on clinical response and tolerance, the daily dose can be increased up to 1,500 mg twice daily, with dose changes made in 500 mg twice daily increments or decrements every two to four weeks. For children aged 4 to 11 years and adolescents aged 12 to 17 years weighing less than 50 kg in add-on therapy: the initial therapeutic dose is 10 mg/kg twice daily; depending on clinical response and tolerance, the daily dose can be increased up to 60 mg/kg daily in two 30 mg/kg doses, with dose changes made in 10 mg/kg twice daily increments or decrements every two weeks. In patients with renal impairment, the daily dose must be individualised according to renal function using creatinine clearance estimation; dosing adjustments apply based on severity of renal impairment.

Key safety warnings

Antiepileptic drugs, including levetiracetam, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication; patients treated with any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour and any unusual changes in mood or behaviour. Pooled analyses of clinical trials showed that patients randomised to antiepileptic drugs had approximately twice the risk of suicidal thinking or behaviour compared to patients randomised to placebo, representing an increase of approximately one case of suicidal thinking or behaviour for every 530 patients treated. Patients, their caregivers, and families should be informed that antiepileptic drugs increase the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about self-harm, with behaviours of concern reported immediately to the treating doctor. Levetiracetam may cause changes in behaviour including aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability, and psychotic symptoms; patients treated with levetiracetam should be monitored for psychiatric signs and symptoms. A paradoxical reaction of worsening of seizure may be observed especially when starting treatment or at increase in dose. Cases of decreased blood cell counts including neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia have been described in association with levetiracetam administration; complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.

Contraindications

Leveriuol is contraindicated in patients with hypersensitivity to levetiracetam or other pyrrolidone derivatives, and in patients with hypersensitivity to any excipients in the tablets.

Regulatory history

Leveriuol was first listed on the Australian Register of Therapeutic Goods on 7 December 2018, with four registered strengths: 250 mg, 500 mg, 750 mg and 1000 mg film-coated tablets.