For doctors

What is it?

Inovelon is a medicine containing the active substance rufinamide. It is available as oval pink tablets containing 100 mg, 200 mg or 400 mg rufinamide.

What is it used for?

Inovelon is used to treat patients aged 4 years or older who have Lennox-Gastaut syndrome, a rare type of epilepsy that usually affects children but which can continue into adulthood. Lennox-Gastaut syndrome is one of the most severe forms of epilepsy in children. Its symptoms include multiple types of seizure (fit), abnormal electrical activity in the brain, learning disability and behavioural problems. Inovelon is used as an add-on to other anti-epileptic medicines.
Because the number of patients with Lennox-Gastaut syndrome is low, the disease is rare, and Inovelon was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 20 October 2004. The medicine can only be obtained with a prescription.

How is it used?

Treatment with Inovelon should be initiated by a paediatrician (a doctor specialised in treating children) or a neurologist (a doctor who treats brain disorders). The doctor should be experienced in the treatment of epilepsy.
The dose of Inovelon depends on the patient’s age and weight and whether the patient is also taking valproate (another anti-epileptic medicine). Treatment generally starts with a daily dose of 200 or 400 mg. This is then adjusted every other day according to the patient’s response to treatment.Inovelon should be taken with water and food twice a day, once in the morning and once in the evening. If the patient cannot swallow the tablets, they can be crushed and mixed in a glass of water. Inovelon should be used with caution by patients who have problems with their liver. For more information, see the Package Leaflet.

How does it work?

The active substance in Inovelon, rufinamide, is an anti-epileptic medicine. It acts by attaching to special channels on the surface of brain cells (sodium channels), which control the electrical activity of the cells. By attaching to the channels, rufinamide prevents them switching from an inactive state to an active state. This dampens down the activity of the brain cells and prevents abnormal electrical activity from spreading through the brain. This reduces the likelihood of a seizure occurring.

How has it been studied?

The effects of Inovelon were first tested in experimental models before being studied in humans. The main study of Inovelon involved 139 patients aged between 4 and 30 years, of whom three quarters were below 17 years old. All of the patients had Lennox-Gastaut syndrome that was not controlled despite continuous treatment for at least 4 weeks with up to 3 other anti-epileptic medicines. The study compared the effects of adding Inovelon or adding a placebo (a dummy treatment) to the other medicines the patients were taking. The main measures of effectiveness were the change in the number of seizures in the 4 weeks after Inovelon or placebo was added, compared with the 4 weeks before it was added, as well as the change in severity of seizures assessed on a 7-point scale by the patient’s parent or guardian.

What benefits has it shown during the studies?

Inovelon caused a reduction in the number and severity of seizures. Patients taking Inovelon had a 35.8% reduction in the total number of seizures, falling from an average of 290 seizures in the 4-week period before Inovelon was started. There was a 1.6% reduction in the patients who added placebo to their existing treatment.
Patients adding Inovelon also had a 42.5% reduction in the number of ‘tonic-atonic’ seizures (a common type of fit in patients with Lennox-Gastaut syndrome that often involves the patient dropping to the floor), compared to a 1.9% increase in those adding placebo.
An improvement in the severity of seizures was reported for about half of the patients adding Inovelon, compared to a third of those adding placebo.

What is the risk associated?

The most common side effects with Inovelon (seen in more than 1 in 10 patients) were somnolence (sleepiness), headache, dizziness, nausea (feeling sick), vomiting, and fatigue (tiredness). For the full list of all side effects reported with Inovelon, see the Package Leaflet.
Inovelon should not be used in patients who may be hypersensitive (allergic) to rufinamide, triazole derivatives (such as some medicines used to treat fungal infections) or any of the other ingredients.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Inovelon’s benefits are greater that its risks for use as adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome in patients 4 years and older. They recommended that Inovelon be given marketing authorisation.

How has it been studied?

The company that makes Inovelon will closely monitor the safety of the medicine. This will include monitoring of cases of ‘status epilepticus’, a dangerous condition where the brain is in a persistent state of seizure. This follows cases of this condition being seen in patients taking Inovelon during its development.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Inovelon to Eisai Limited on 16 January 2007.

The summary of opinion of the Committee for Orphan Medicinal Products for Inovelon is available here.

Name

Inovelon 400 mg film-coated tablets

Composition

400 mg
Each film-coated tablet contains 400 mg rufinamide.
Excipient: 80 mg lactose monohydrate/film coated tablet.

For a full list of excipients, see Section 6.1.

Pharmaceutical Form

Film-coated tablet.

400 mg
Pink, ‘ovaloid’, slightly convex, scored on both sides, embossed ‘-263’ on one side and blank on the other side.

The tablet can be divided into equal halves.