Inovelon^® (Tablets) Instructions for Use

Marketing Authorization Holder

Eisai Europe, Limited (United Kingdom)

Manufactured By

Bushu Pharmaceuticals, Ltd. (Japan)

Packaging and Quality Control Release

EISAI MANUFACTURING, LTD. (United Kingdom)

ATC Code

N03AF03 (Rufinamide)

Active Substance

Rufinamide (Rec.INN registered WHO)

Dosage Forms

	Inovelon®	Tablets, film-coated, 100 mg: 10 pcs.
		Tablets, film-coated, 200 mg: 50 or 60 pcs.
		Tablets, film-coated, 400 mg: 50, 60 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets, film-coated, pale pink oval biconvex with scores on both sides and engraving “Є 261” on one side.

Auxiliary substances : sodium lauryl sulfate, corn starch, hypromellose, lactose monohydrate – 20 mg, microcrystalline cellulose PH-102, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate.

Composition of the film coating opadry 00F44042 (hypromellose, macrogol-8000, titanium dioxide, talc, iron oxide red).

10 pcs. – blisters (1) – carton packs.

The pack opening areas are sealed with two transparent protective stickers.

Tablets, film-coated, pale pink oval biconvex with scores on both sides and engraving “Є 262” on one side.

Auxiliary substances : sodium lauryl sulfate, corn starch, hypromellose, lactose monohydrate – 40 mg, microcrystalline cellulose PH-102, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate.

Composition of the film coating opadry 00F44042 (hypromellose, macrogol-8000, titanium dioxide, talc, iron oxide red).

10 pcs. – blisters (5) – carton packs.
10 pcs. – blisters (6) – carton packs.

The pack opening areas are sealed with two transparent protective stickers.

Tablets, film-coated, pale pink oval biconvex with scores on both sides and engraving “Є 263” on one side.

Auxiliary substances : sodium lauryl sulfate, corn starch, hypromellose, lactose monohydrate – 80 mg, microcrystalline cellulose PH-102, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate.

Composition of the film coating opadry 00F44042 (hypromellose, macrogol-8000, titanium dioxide, talc, iron oxide red).

10 pcs. – blisters (5) – carton packs.
10 pcs. – blisters (6) – carton packs.
10 pcs. – blisters (10) – carton packs.

The pack opening areas are sealed with two transparent protective stickers.

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic drug, carboxamide derivative

Indications

• Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients 1 year of age and older.
• Treatment of focal (partial) onset seizures with or without secondary generalization in adults and adolescents from 12 years of age.

The initiation of treatment should be supervised by a physician experienced in the management of epilepsy. Rufinamide is indicated as an adjunctive therapy and is used in combination with other antiepileptic drugs. The decision to prescribe Inovelon should be based on an individual assessment of the patient’s condition and treatment response.

Efficacy was established in placebo-controlled clinical trials in patients with Lennox-Gastaut syndrome and in patients with focal seizures. The demonstrated efficacy in LGS was primarily in the reduction of tonic-atonic seizures (drop attacks).

Contraindications

• Hypersensitivity to the active substance (rufinamide), to any of the excipients listed in the “Dosage Form, Packaging, and Composition” section, or to other carboxamide derivatives (e.g., carbamazepine, oxcarbazepine).
• Patients with familial short QT syndrome or with a known history of this condition. Rufinamide has been shown to shorten the QT interval, and its use is contraindicated in individuals with this specific cardiac conduction abnormality.
• Severe hepatic impairment (Child-Pugh class C). The pharmacokinetics and safety of rufinamide have not been studied in this patient population, and use is therefore contraindicated.
• Pregnancy unless clearly necessary and after careful consideration of the benefits and risks by a specialist. Adequate contraception is required in women of childbearing potential.

Prior to initiating treatment, a thorough patient history should be taken to rule out any contraindications. If a hypersensitivity reaction occurs during therapy, the drug must be discontinued immediately and appropriate medical management instituted.

Dosage Regimen

Dosage for Lennox-Gastaut Syndrome (Patients 1 year of age and older): Treatment should be initiated at a daily dose of approximately 10 mg/kg body weight, administered in two equally divided doses. The dose should be titrated upward by approximately 10 mg/kg increments every other day to a target maintenance dose of 45 mg/kg/day, administered in two equally divided doses. The maximum recommended daily dose is 45 mg/kg. The effective dose in clinical trials ranged from 20 mg/kg/day to 45 mg/kg/day. Doses above 45 mg/kg/day have not been shown to confer additional benefit and are associated with an increased incidence of adverse reactions.

Dosage for Focal Seizures (Adults and Adolescents from 12 years of age): Treatment should be initiated at a dose of 400 mg to 800 mg per day, administered in two equally divided doses. The dose should be increased by 400 mg to 800 mg every two days until a maximum daily dose of 3200 mg to 3600 mg, administered in two equally divided doses, is reached. The recommended maintenance dose is 3200 mg/day. The dose should be individualized based on clinical response and tolerability.

Administration: Inovelon tablets should be administered with food. The tablets can be swallowed whole with water or, for patients who have difficulty swallowing, the tablets may be halved at the score line or crushed and administered in a small amount of liquid or soft food (e.g., applesauce) immediately prior to administration. The film coating is intended to make the tablet easier to swallow and does not affect the release of the active ingredient.

Special Populations: In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), caution is advised and a dose reduction may be necessary. Rufinamide is not recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min) as there is no clinical experience in this population. No dose adjustment is required for the elderly based on age alone, but caution should be exercised due to the greater frequency of decreased hepatic, renal, or cardiac function. Dose adjustments should be considered when co-administered with strong CYP450 enzyme inducers (e.g., carbamazepine, phenytoin, phenobarbital, primidone) as they may decrease rufinamide plasma concentrations.

Adverse Reactions

Very common (≥1/10) adverse reactions include headache, dizziness, fatigue, somnolence, nausea, and vomiting. These events are often dose-related and may be more frequent during the initial phase of treatment or following a dose increase. They often diminish with continued therapy.

Common (≥1/100 to <1/10) adverse reactions include influenza, nasopharyngitis, otitis media, decreased appetite, aggression, agitation, anxiety, insomnia, status epilepticus, ataxia, tremor, nystagmus, psychomotor hyperactivity, blurred vision, diplopia, constipation, dyspepsia, abdominal pain, rash, pruritus, back pain, gait disturbance, and elevated liver enzymes (transaminases).

Uncommon (≥1/1,000 to <1/100) adverse reactions include leukopenia, neutropenia, suicidal ideation, urticaria, alopecia, and nephrolithiasis. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Serious skin reactions, including Stevens-Johnson Syndrome (SJS), have been reported very rarely. Therapy should be discontinued if a serious skin reaction is suspected.

QT Shortening: Rufinamide causes a dose-dependent shortening of the QT interval. The clinical significance of this effect is unknown, but it is contraindicated in patients with familial short QT syndrome. Caution should be exercised in patients with known cardiac conduction abnormalities or those taking other medications that shorten the QT interval.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in association with rufinamide therapy. This potentially life-threatening condition is characterized by fever, rash, lymphadenopathy, and involvement of various organs. If DRESS is suspected, Inovelon should be discontinued immediately.

Drug Interactions

Effects of Other Drugs on Rufinamide: Strong cytochrome P450 (CYP) enzyme inducers such as carbamazepine, phenytoin, phenobarbital, and primidone can significantly increase the clearance of rufinamide, leading to reduced rufinamide plasma concentrations. Dose adjustment of rufinamide may be necessary when initiating or discontinuing therapy with these agents. Valproate may decrease the clearance of rufinamide, potentially increasing its plasma levels; however, no dose adjustment is routinely recommended.

Effects of Rufinamide on Other Drugs: Rufinamide is a weak inducer of CYP 3A4 enzymes and may therefore reduce the plasma concentrations of substrates of this enzyme. This can lead to decreased efficacy of drugs such as oral contraceptives (ethinylestradiol, norethindrone), triazolam, midazolam, simvastatin, and atorvastatin. Women using hormonal contraception should be advised to use additional non-hormonal methods of birth control. Rufinamide may decrease the plasma concentrations of carbamazepine while increasing the concentrations of its active metabolite. Rufinamide can significantly increase plasma concentrations of phenytoin; it is recommended to monitor phenytoin levels and consider a dose reduction of phenytoin when rufinamide is initiated.

Other Interactions: Caution is advised when co-administering rufinamide with other central nervous system (CNS) depressants, including alcohol, barbiturates, and benzodiazepines, due to the potential for additive sedative effects. The tablets contain lactose; patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Overdose

Symptoms: Overdose with rufinamide has been reported. The symptoms are primarily related to the central nervous system and the gastrointestinal tract. Observed signs and symptoms of overdose include headache, dizziness, somnolence, nausea, and vomiting. More severe cases may involve ataxia, diplopia, and QT interval shortening on the electrocardiogram (ECG). Status epilepticus has also been reported in the context of overdose.

Management: There is no specific antidote for rufinamide overdose. General supportive measures should be instituted, including gastric lavage if performed soon after ingestion or the administration of activated charcoal to reduce further absorption. Close monitoring of vital signs and cardiac function (including ECG) is recommended. Hemodialysis is unlikely to be effective due to the high protein binding of rufinamide (>95%). The patient should be managed in a setting equipped for supportive care and seizure control. In case of massive overdose, the possibility of multiple drug involvement should be considered.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.