RUFINAMIDE EISAI

Treatment with rufinamide should be initiated by a physician specialised in paediatrics or neurology with experience in the treatment of epilepsy. Rufinamide Eisai oral suspension and Rufinamide Eisai film-coated tablets may be interchanged at equal doses.

Patients should be monitored during the switch over period. 25 ml/kg/day) administered in two equally divided doses separated by approximately 12 hours. 125 ml/kg/day) administered in two equally divided doses separated by approximately 12 hours.

125 ml/kg/day).

Patients receiving valproate:

As valproate significantly decreases clearance of rufinamide, a lower maximum dose of rufinamide is recommended for patients being co-administered valproate. 25 ml/kg/day) administered in two equally divided doses separated by approximately 12 hours.

75 ml/kg/day) administered in two equally divided doses separated by approximately 12 hours. 75 ml/kg/day). 5 ml of rufinamide. 5 ml doses, one in the morning and one in the evening). According to clinical response and tolerability, the dose may be increased by 200 mg/day increments, as frequently as every third day, up to a maximum recommended dose of 1,000 mg/day (25 ml/day).

Doses of up to 3,600 mg/day (90 ml/day) have been studied in a limited number of patients.

Patients < 30 kg also receiving valproate:

As valproate significantly decreases clearance of rufinamide, a lower maximum dose of rufinamide is recommended for patients < 30 kg being co-administered valproate. Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, after a minimum of 2 days the dose may be increased by 200 mg/day, to the maximum recommended dose of 600 mg/day (15 ml/day).

Use in adults, adolescents and children 4 years of age or older of 30 kg or over Patients > 30 kg not receiving valproate: Treatment should be initiated at a daily dose of 400 mg (10 ml dosing suspension given as two 5 ml doses). According to clinical response and tolerability, the dose may be increased by 400 mg/day increments, as frequently as every other day, up to a maximum recommended dose as indicated in the table below.

Summary of the safety profile The clinical development program has included over 1,900 patients, with different types of epilepsy, exposed to rufinamide. The most commonly reported adverse reactions overall were headache, dizziness, fatigue, and somnolence.

The most common adverse reactions observed at a higher incidence than placebo in patients with Lennox-Gastaut syndrome were somnolence and vomiting. Adverse reactions were usually mild to moderate in severity. 2% for patients receiving rufinamide and 0% for patients receiving placebo.

The most common adverse reactions resulting in discontinuation from the rufinamide treatment group were rash and vomiting. Tabulated list of adverse reactions Adverse reactions reported with an incidence greater than placebo, during the Lennox-Gastaut syndrome double-blind studies or in the overall rufinamide-exposed population, are listed in the table below by MedDRA preferred term, system organ class and by frequency.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000). 4. Additional information on special populations System Organ Class Very Common Common Uncommon Rare Pneumonia Influenza Nasopharyngitis Ear infection Sinusitis Infections and infestations Rhinitis Immune system disorders Hypersensitivity* AnorexiaMetabolism and nutrition disorders Eating disorder Decreased appetite Anxiety Insomnia Psychiatric disorders Somnolence* Status epilepticus* Headache Convulsion Dizziness* Coordination Abnormal* Nystagmus Psychomotor hyperactivity Nervous system disorders Tremor Diplopia Vision blurred Eye Disorders Ear and Labyrinth disorders Vertigo Respiratory, thoracic and mediastinal disorders Epistaxis Nausea Abdominal pain upper Vomiting Constipation Gastrointestinal disorders Dyspepsia Diarrhoea Hepatobiliary disorders Hepatic enzyme increase Skin and subcutaneous tissue disorders Rash* Acne Musculoskeletal and connective tissue and bone disorders Back pain Reproductive system and breast disorders Oligomenorrhoea General disorders and administration site conditions Fatigue Gait disturbance* Investigations Weight decrease Head injuryInjury, poisoning and procedural complications Contusion Paediatric Population (age 1 to less than 4 years) In a multicentre, open-label study comparing the addition of rufinamide to any other AED of the investigator’s choice to the existing regimen of 1 to 3 AEDs in paediatric patients, 1 to less than 4 years of age with inadequately controlled LGS, 25 patients, of which 10 subjects were aged 1 to 2 years, were exposed to rufinamide as adjunctive therapy for 24 weeks at a dose of up to 45 mg/kg/day, in 2 divided doses.

Status epilepticus Status epilepticus cases have been observed during treatment with rufinamide in clinical development studies, whereas no such cases were observed with placebo. These events led to rufinamide discontinuation in 20% of the cases.

If patients develop new seizure types and/or experience an increased frequency of status epilepticus that is different from the patient’s baseline condition, then the benefit-risk ratio of the therapy should be reassessed. Withdrawal of rufinamide Rufinamide should be withdrawn gradually to reduce the possibility of seizures on withdrawal.

In clinical studies discontinuation was achieved by reducing the dose by approximately 25% every two days. There are insufficient data on the withdrawal of concomitant antiepileptic medicinal products once seizure control has been achieved with the addition of rufinamide.

8). Patients and carers should exercise caution until they are familiar with the potential effects of this medicinal product. Hypersensitivity reactions Serious antiepileptic medicinal product hypersensitivity syndrome including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and Stevens-Johnson syndrome have occurred in association with rufinamide therapy.

Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations included lymphadenopathy, liver function tests abnormalities, and haematuria.

As the disorder is variable in its expression, other organ system signs and symptoms not noted here may occur. The antiepileptic drug (AED) hypersensitivity syndrome occurred in close temporal association to the initiation of rufinamide therapy and in the paediatric population.

If this reaction is suspected, rufinamide should be discontinued and alternative treatment started. All patients who develop a rash while taking rufinamide must be closely monitored. QT shortening In a thorough QT study, rufinamide produced a decrease in QTc interval proportional to concentration.

1.