LEVETIRACETAM-AFT

What it is

LEVETIRACETAM-AFT is available as a 100 mg/mL oral solution and a 500 mg/5 mL concentrate solution for intravenous infusion. The oral solution is a clear, colourless solution. The concentrate solution for infusion is a clear, colourless, sterile solution. The concentrate solution for IV infusion is an alternative for patients when oral administration is temporarily not feasible.

Approved indications —

Use in epileptic patients aged 4 years and older, initially as add-on therapy, in the treatment of partial onset seizures with or without secondary generalisation. — 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 (JME). — 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 (IGE).

Dosing overview

For monotherapy, the recommended starting dose is 250 mg twice daily, increased to 500 mg twice daily after 2 weeks, with further increases of 250 mg twice daily possible every two weeks depending on response, up to a maximum dose of 1500 mg twice daily. For add-on therapy in adults and adolescents aged 12–17 years weighing 50 kg or more, the therapeutic dose is 500 mg twice daily, which can be started on the first day of treatment, with dose increases up to 1500 mg twice daily possible depending on clinical response and tolerance, with dose changes in 500 mg twice daily increments every 2 to 4 weeks. For children aged 4–11 years and adolescents aged 12–17 years weighing less than 50 kg, the initial therapeutic dose is 10 mg/kg twice daily, with increases up to 60 mg/kg daily possible depending on response, in 10 mg/kg twice daily increments every two weeks. For patients with renal impairment, the daily dose must be individualised according to renal function based on creatinine clearance, with normal renal function receiving 500–1500 mg twice daily, mild impairment receiving 500–1000 mg twice daily, moderate impairment receiving 250–750 mg twice daily, and severe impairment receiving 250–500 mg twice daily.

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 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 199 placebo-controlled clinical trials showed that patients randomised to an antiepileptic drug had approximately twice the risk of suicidal thinking or behaviour compared to placebo, with an estimated incidence rate of 0.43% among antiepileptic drug-treated patients compared to 0.24% among placebo-treated patients. If levetiracetam has to be discontinued, it is recommended to withdraw it gradually. Levetiracetam concentrate solution for IV infusion should not be administered by rapid infusion or direct IV injection. Due to possible different individual sensitivity, some patients might experience somnolence or other central nervous system-related symptoms at the beginning of treatment or following a dosage increase, and caution is recommended when performing skilled tasks such as driving vehicles or operating machinery. The oral solution includes methylhydroxybenzoate and propylhydroxybenzoate which may cause allergic reactions (possibly delayed) and maltitol which may have a mild laxative effect. Patients with rare hereditary problems of fructose intolerance should not take the oral solution.

Contraindications

Hypersensitivity to levetiracetam or other pyrrolidone derivatives or any of the excipients.

PBS listing

The oral solution 100 mg per mL, 300 mL is listed on the PBS with 2 items under a restricted authority required restriction, at an ex-manufacturer price of A$60.12.

Regulatory history

LEVETIRACETAM-AFT was first registered on the ARTG on 7 November 2014, with registration of both the 100 mg/mL oral solution (ARTG 218279) and the 500 mg/5 mL concentrate solution for infusion (ARTG 218280).