INOVELON

What it is

Inovelon is a film-coated tablet containing rufinamide in strengths of 100 mg, 200 mg, or 400 mg. Rufinamide modulates the activity of sodium channels, prolonging their inactive state. Inovelon is for oral use and should be taken twice daily in the morning and in the evening, in two equally divided doses.

Approved indications

— Adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome in patients 4 years of age and older.

Dosing overview

Inovelon should be taken twice daily in two equally divided doses, one in the morning and one in the evening. Inovelon should be administered with food. Dosing depends on body weight and concomitant use of valproate. For children under 30 kg not receiving valproate, treatment should be initiated at a total daily dose of 200 mg, with increases of 200 mg/day every third day up to a maximum recommended total daily dose of 1000 mg/day. For children under 30 kg receiving valproate, treatment should be initiated at 200 mg daily, with increases of 200 mg/day after a minimum of two days to a maximum recommended total daily dose of 600 mg/day. For patients 30 kg or over not receiving valproate, treatment should be initiated at 400 mg daily, with increases of 400 mg/day every other day. Maximum recommended daily doses are 1800 mg for 30.0–50.0 kg, 2400 mg for 50.1–70.0 kg, and 3200 mg for 70.1 kg or more. For patients 30 kg or over receiving valproate, treatment should be initiated at 400 mg daily, with increases of 400 mg/day every other day to maximum recommended daily doses of 1200 mg, 1600 mg, or 2200 mg depending on weight.

Key safety warnings

Status epilepticus cases have been observed during treatment with Inovelon in clinical development studies. If patients develop new seizure types and/or experience an increased frequency of status epilepticus that is different from baseline, the benefit-risk ratio of therapy should be reassessed. Serious antiepileptic medicinal product hypersensitivity syndrome including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and Stevens-Johnson syndrome have occurred with Inovelon therapy. Signs typically presented with fever and rash associated with other organ system involvement, including lymphadenopathy, liver function test abnormalities, and haematuria. All patients who develop a rash while taking Inovelon must be closely monitored. Inovelon produced a decrease in QTc interval proportional to concentration. Clinicians should use clinical judgment when assessing whether to prescribe Inovelon to patients at risk from further shortening their QTc duration, such as those with Congenital Short QT Syndrome or a family history of such a syndrome. Inovelon treatment has been associated with dizziness, somnolence, ataxia and gait disturbances, which could increase the occurrence of accidental falls. Patients and carers should exercise caution until they are familiar with the potential effects of this medicinal product. Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents. A meta-analysis has shown a small increased risk of suicidal ideation and behaviour, and the available data do not exclude the possibility of an increased risk for Inovelon. Patients should be monitored for signs of suicidal ideation and behaviours.

Contraindications

Hypersensitivity to the active substance, triazole derivatives or to any of the excipients is a contraindication. Inovelon should not be used in patients with severe hepatic impairment.

Regulatory history

Inovelon rufinamide was first registered on the ARTG on 2018-06-27 in three strengths: 100 mg, 200 mg, and 400 mg film-coated tablets. The TGA approved Inovelon on 2018-06-22 as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome in patients 4 years of age and older. The approval followed the resolution of minor quality issues and positive nonclinical findings, reflecting the drug's demonstrated anticonvulsant effect in addressing a severe childhood epilepsy syndrome.