Banzel: Indications, Dosage, Precautions, Adverse Effects
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Banzel - Product Information

Manufacture: Eisai Inc.
Country: Canada
Condition: Epilepsy, Lennox-Gastaut Syndrome, Seizures (Convulsions)
Class: Anticonvulsants
Form: Tablets
Ingredients: rufinamide, colloidal silicon dioxide, corn starch crosscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulphate, iron oxide red, polyethylene glycol, talc, and titanium dioxide.

Rufinamide Tablets

Summary Product Information

Route of
Administration
Dosage Form /
Strength
Non-medicinal Ingredients
Oral tablet

100 mg, 200 mg, 400 mg
colloidal silicon dioxide, corn starch, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulphate

Indications and Clinical Use

BANZEL (rufinamide) is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults.

In a placebo-controlled clinical trial of 12 weeks in duration in patients with Lennox-Gastaut syndrome, BANZEL decreased the frequency of total seizures, tonic-atonic seizures (drop attacks), and seizure severity.

BANZEL is not indicated for the treatment of any other type of seizure disorder.

Geriatrics (>65 years of age):There is limited information on the use of BANZEL in subjects over 65 years of age. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see WARNINGS AND PRECAUTIONS, Special Populations).

Pediatrics (<4 years of age):The safety and efficacy of BANZEL in children under 4 years of age with Lennox-Gastaut syndrome have not been studied. BANZEL is not indicated for use in this patient population (see WARNINGS AND PRECAUTIONS, Special Populations).

Contraindications

  • Patients with Familial Short QT syndrome, family history of short QT syndrome, presence, or history of short QT interval (see WARNINGS AND PRECAUTIONS, QT Shortening).
  • Patients who are hypersensitive to rufinamide, triazole derivatives or any of the excipients (e.g., Parabens; see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION). For a complete listing, see Dosage Forms, Composition and Packaging section.

Warnings and Precautions

Cardiovascular

QT Shortening

Formal cardiac ECG studies demonstrated shortening of the QT interval (mean = 20 msec, for doses ≥2400 mg twice daily) with BANZEL treatment. In a placebo-controlled study of the QT interval in 117 healthy subjects, a higher percentage of BANZEL-treated subjects (46% at 2400 mg, 46% at 3200 mg, and 65% at 4800 mg) had a QT shortening of greater than 20 msec at Tmax compared to placebo (5 - 10%). In this placebo-controlled study, a moderate rise in heart rate was induced by rufinamide in only the four subjects who received the maximum dose of 7200 mg/day. Reductions of the QT interval below 300 msec were not observed.

The degree of QT shortening induced by BANZEL is without any known clinical risk. Familial Short QT syndrome is associated with an increased risk of sudden death and ventricular arrhythmias, particularly ventricular fibrillation. Such events in this syndrome are believed to occur primarily when the corrected QT interval falls below 300 msec. Nonclinical data also indicate that QT shortening is associated with ventricular fibrillation.

The degree of QT shortening induced by BANZEL is without any known clinical risk. Familial Short QT syndrome is associated with an increased risk of sudden death and ventricular arrhythmias, particularly ventricular fibrillation. Such events in this syndrome are believed to occur primarily when the corrected QT interval falls below 300 msec. Nonclinical data also indicate that QT shortening is associated with ventricular fibrillation.

Patients with Familial Short QT syndrome, family history of short QT syndrome, and presence, or history of short QT interval should not be treated with BANZEL (see CONTRAINDICATIONS). Caution should be used when administering BANZEL with other drugs or products that may shorten the QT interval (e.g., digoxin, mexiletine, phenytoin, magnesium sulfate).

Dependence/Tolerance

The abuse and dependence potential of BANZEL has not been evaluated in humans. Studies in Cynomolgus monkeys have shown no potential for physical or psychological dependence.

Endocrine and Metabolism

BANZEL contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Neurologic

Withdrawal of AEDs

As with all antiepileptic drugs, BANZEL should be withdrawn gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. If abrupt discontinuation of the drug is medically necessary, the transition to another AED should be made under close medical supervision. In clinical trials, BANZEL discontinuation was achieved by reducing the dose by approximately 25% every two days.

Status Epilepticus

Cases of status epilepticus have been reported during various controlled clinical trials of BANZEL. In the controlled Lennox Gastaut syndrome (LGS) trial, 3 of 74 (4%) BANZEL-treated patients experienced status epilepticus compared to none of the 64 placebo-treated patients. In all controlled trials that included patients with different epilepsies, 11 of 1240 (1%) BANZEL-treated patients experienced status epilepticus compared to none of the 635 placebo-treated patients. In these trials, nearly 20% of the patients that had status epilepticus discontinued from study. In cases where the patient develops new seizure type(s) and/or experiences an increased frequency of status epilepticus, the risk-benefit ratio of continued rufinamide therapy should be reassessed. Status epilepticus has been reported post-market (see ADVERSE REACTIONS).

Dizziness and Ataxia

In the controlled LGS trial, 2 of 74 (3%) BANZEL-treated patients experienced dizziness compared to none of the 64 placebo-treated patients. Four BANZEL-treated patients (5%) experienced ataxia compared to none of the placebo-treated patients (see ADVERSE REACTIONS).

In all other controlled trials that included patients with different epilepsies, dizziness was experienced in 190 of 1166 (16%) BANZEL-treated patients compared to 60 of 571 (11%) placebo-treated patients. Thirty-nine BANZEL-treated patients (3%) experienced ataxia compared to 3 (1%) of the placebo-treated patients.

Patients should be advised about the potential for somnolence or dizziness and advised not to drive or operate machinery until they have gained sufficient experience on BANZEL to gauge whether it affects their mental and/or motor performance.

Somnolence and Fatigue

In the controlled LGS trial 18 BANZEL-treated patients (24%) experienced somnolence compared to 8 (13%) of the placebo-treated patients. Seven BANZEL-treated patients (10%) experienced fatigue compared to 5 (8%) of the placebo-treated patients.

In all other controlled trials that included patients with different epilepsies, somnolence was experienced by 128 (11%) of BANZEL-treated patients compared to 50 (9%) of the placebo-treated patients. Fatigue was experienced by 162 (14%) of the BANZEL-treated patients compared to 52 (9%) of the placebo-treated patients.

Ophthalmological Effects

In the controlled LGS trial, BANZEL treatment was associated with vision-related adverse events such as diplopia, dry eye, eye infection, eye irritation, eye pruritus, and blurred vision all at an incidence of 1% compared to 0% in the placebo-treated patients. Nystagmus occurred in 4% of the BANZEL-treated patients compared to 0% in the placebo-treated patients. None of the BANZEL-treated patients discontinued treatment due to vision-related adverse events (see ADVERSE REACTIONS).

In all other controlled trials that included patients with different epilepsies, BANZEL treatment was associated with vision-related adverse events such as diplopia (7%), blurred vision (4%) and nystagmus (4%) compared to 2%, 2% and 3%, respectively, for patients who received placebo.

Psychiatric

Suicidal Ideation and Behaviour

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications.

All patients treated with antiepileptic drugs, irrespective of indication, should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

An FDA meta-analysis of randomized placebo-controlled trials, in which antiepileptic drugs were used for various indications, has shown a small increased risk of suicidal ideation and behaviour in patients treated with these drugs. The mechanism of this risk is not known.

There were 43,892 patients treated in the placebo-controlled clinical trials that were included in the meta-analysis. Approximately 75% of patients in these clinical trials were treated for indications other than epilepsy and, for the majority of non-epilepsy indications the treatment (antiepileptic drug or placebo) was administered as monotherapy. Patients with epilepsy represented approximately 25% of the total number of patients treated in the placebo-controlled clinical trials and, for the majority of epilepsy patients, treatment (antiepileptic drug or placebo) was administered as adjunct to other antiepileptic agents (i.e., patients in both treatment arms were being treated with one or more antiepileptic drug). Therefore, the small increased risk of suicidal ideation and behaviour reported from the meta-analysis (0.43% for patients on antiepileptic drugs compared to 0.24% for patients on placebo) is based largely on patients that received monotherapy treatment (antiepileptic drug or placebo) for non-epilepsy indications. The study design does not allow an estimation of the risk of suicidal ideation and behaviour for patients with epilepsy that are taking antiepileptic drugs, due both to this population being the minority in the study, and the drug-placebo comparison in this population being confounded by the presence of adjunct antiepileptic drug treatment in both arms.

Sensitivity/Resistance

Multi-organ hypersensitivity syndrome (also known as Drug Rash Eosinophilia and Systemic Symptoms or DRESS), a serious condition sometimes induced by antiepileptic drugs, has occurred in association with BANZEL therapy in clinical trials. One patient experienced rash, urticaria, facial edema, fever, elevated eosinophils, stuporous state, and severe hepatitis, beginning on Day 29 of BANZEL therapy and extending over a course of 30 days of continued BANZEL therapy. Symptoms resolved 11 days after BANZEL discontinuation. Four additional possible cases presented with rash and one or more of the following: fever, elevated liver function tests, hematuria, and lymphadenopathy. These symptoms occurred in children under 12 years of age, within four weeks of treatment initiation, and were noted to resolve and/or improve upon BANZEL discontinuation. This syndrome has been reported with other anticonvulsants and typically, although not exclusively, presents with fever and rash associated with other organ system involvement that may or may not include eosinophilia, hepatitis, nephritis, lymphadenopathy, and/or myocarditis. Because this disorder is variable in its expression, other organ system signs and symptoms not noted here may occur. In addition rare cases of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and Stevens-Johnson syndrome have been reported in association with BANZEL therapy post marketing. If an antiepileptic drug hypersensitivity syndrome is suspected, BANZEL should be discontinued and alternative treatment started.

All patients who develop a rash while taking BANZEL must be closely supervised.

Special Populations

Women of Childbearing Potential:Women of childbearing potential should be warned that the concurrent use of BANZEL with hormonal contraceptives may render this method of contraception less effective (see DRUG INTERACTIONS). Additional non-hormonal forms of contraception are recommended when using BANZEL.

Pregnant Women:Rufinamide produced developmental toxicity when administered orally to pregnant animals at clinically relevant doses, based on systemic exposure. The no-effect doses for adverse effects are associated with plasma AUCs approximately 0.2 times that in humans at the maximum recommended human dose (MRHD, 3200 mg) and the high doses are associated with plasma AUCs 1.5 to 2 times the human plasma AUC at the MRHD. There are no adequate and well-controlled studies in pregnant women. BANZEL should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. If women decide to become pregnant while taking BANZEL, the use of this product should be carefully re-evaluated.

Labour and Delivery

The effect of BANZEL on labor and delivery in humans is not known.

Pregnancy Registry

Physicians are advised to recommend that pregnant patients taking BANZEL enroll in the North American Antiepileptic Drug Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the following website: http://www.aedpregnancyregistry.org/

Nursing Women:Rufinamide is likely to be excreted in breast milk. Because of the potential for serious adverse reactions from BANZEL in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Pediatrics (<4 years of age):The safety and efficacy of BANZEL in children under 4 years of age with Lennox-Gastaut syndrome have not been studied. BANZEL is not indicated for use in this patient population.

Geriatrics (>65 years of age):Clinical studies of BANZEL did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

A study evaluating the pharmacokinetics of rufinamide in elderly subjects showed that there were no significant differences in the plasma and urine pharmacokinetic parameters of rufinamide between the younger and elderly subjects under both single and multiple dose treatments (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions).

Adverse Reactions

Adverse Drug Reaction Overview

Placebo-controlled double-blind studies were conducted in adults and in pediatric patients (>4 years of age) in other forms of epilepsy in addition to the trial in Lennox-Gastaut syndrome (LGS). BANZEL has been administered to 1978 patients during all epilepsy clinical trials (placebo-controlled and open-label). The safety profile was similar across different epilepsy populations. Overall, the most commonly observed (≥10%) adverse reactions in BANZEL-treated epilepsy patients at all doses studied (200 to 3200 mg/day) with a higher frequency than in placebo were headache, dizziness, fatigue, somnolence and nausea. At the target dose of 45 mg/kg/day in children, the most common (≥5%) adverse reactions were somnolence, vomiting, headache, fatigue, dizziness, nausea, influenza, nasopharyngitis and decreased appetite. At doses up to 3200 mg/day in adults, the most common (≥5%) adverse reactions were headache, dizziness, fatigue, nausea, somnolence, diplopia, tremor, nystagmus, vision blurred, and vomiting. These adverse reactions were usually mild to moderate and transient in nature. In controlled double-blind clinical studies, 8.1% (100/1240) of patients receiving BANZEL as adjunctive therapy and 4.3% (27/635) receiving placebo discontinued as a result of an adverse reaction. In the LGS trial, 8.1% (6/74) BANZEL-treated patients discontinued from the study due to adverse events compared with none of the 64 placebo-treated patients.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Lennox-Gastaut Syndrome

Somnolence, dizziness, ataxia and gait disturbance were common central nervous system reactions in the controlled trial of patients 4 years or older with Lennox-Gastaut syndrome treated with BANZEL as adjunctive therapy. Vomiting and pyrexia were also commonly reported adverse reactions (see WARNINGS AND PRECAUTIONS, Neurologic).

Somnolence was reported in 24% of BANZEL-treated patients compared to 13% of placebo patients. Fatigue was reported in 10% of BANZEL-treated patients compared to 8% of placebo patients. Dizziness was reported in 3% of BANZEL-treated patients compared to 0% of placebo patients. Ataxia and gait disturbance were reported in 5% and 1% of BANZEL-treated patients, respectively, and in no placebo patients. Balance disorder and abnormal coordination were each reported in 0% of BANZEL-treated patients and 2% of placebo patients.

Table 1: Incidence (%) of Treatment-Emergent Adverse Reactions in the Lennox-Gastaut Syndrome Study by Preferred Term for All Treated Patients. (Adverse Reactions occurred in at least 1% of BANZEL-treated patients and occurred more frequently than in Placebo Patients)
System Organ Class / Preferred
Term
Placebo
(N=64)
%
BANZEL
(N=74)
%
Blood and lymphatic system disorders
Ecchymosis 0 1
Petechiae 0 1
Ear and labyrinth disorders
Ear Infection 2 4
Endocrine disorders
Hypothyroidism 0 1
Eye disorders
Diplopia 0 1
Dry Eye 0 1
Eye Infection 0 1
Eye Irritation 0 1
Eye Pruritus 0 1
Periorbital Oedema 0 1
Vision Blurred 0 1
Gastrointestinal disorders
Vomiting 6 22
Loose Stools 2 3
Gingival Swelling 0 1
Halitosis 0 1
Nausea 0 1
Oesophagitis 0 1
Salivary Hypersecretion 0 1
General disorders and administration site conditions
Fatigue 8 10
Ataxia 0 5
Difficulty in Walking 0 1
Gait Abnormal 0 1
Intermittent Pyrexia 0 1
Immune system disorders
Bronchospasm 0 1
Infections and infestations
Nasopharyngitis 3 10
Rhinitis 5 5
Sinusitis 2 3
Influenza 0 3
Pneumonia 0 3
Bronchitis Acute 0 1
Cellulitis 0 1
Croup Infectious 0 1
Folliculitis 0 1
Herpes Viral Infection 0 1
Hordeolum 0 1
Periorbital Cellulitis 0 1
Rubella 0 1
Injury, poisoning and procedural complications
Contusion 2 3
Head Injury 2 3
Arthropod Bite 0 1
Drug Toxicity 0 1
Ligament Injury 0 1
Skin Laceration 0 1
Post Procedural Complication 0 1
Investigations
Liver Function Test Abnormal 0 1
Respiratory Rate Increased 0 1
Metabolism and nutrition disorders
Decreased Appetite 5 10
Musculoskeletal and connective tissue disorders
Back Disorder 0 1
Musculoskeletal Stiffness 0 1
Myalgia 0 1
Nervous system disorders
Somnolence 13 24
Headache 5 7
Psychomotor Hyperactivity 3 4
Nystagmus 0 4
Status Epilepticus 0 4
Convulsions 0 3
Dizziness 0 3
Abasia 0 1
Aphasia 0 1
Crying 0 1
Tension Headache 0 1
Tonic Convulsion 0 1
Psychiatric disorders
Eating Disorder 0 3
Disorientation 0 1
Hostility 0 1
Renal and urinary disorders
Enuresis 0 1
Micturition Frequency Decreased 0 1
Urinary Retention 0 1
Reproductive system and breast disorders
Menses Delayed 0 3
Respiratory, thoracic and mediastinal disorders
Epistaxis 0 4
Excessive bronchial secretion 0 1
Pharyngolaryngeal Pain 0 1
Rhinitis Seasonal 0 1
Stridor 0 1
Skin and subcutaneous tissue disorders
Rash 2 7
Acne 0 3
Exanthem 0 3
Dermatitis Contact 0 1
Dry Skin 0 1
Swelling Face 0 1
Vascular disorders
Pallor 0 1

Controlled Clinical Studies in All Indications

Pediatrics

Table 2 lists treatment-emergent adverse reactions that occurred in at least 1% of pediatric patients with epilepsy treated with BANZEL in controlled adjunctive studies and were numerically more common in patients treated with BANZEL than placebo.

Table 2: Incidence (%) of Treatment-Emergent Adverse Reactions in All Pediatric (4 to 16 years) Double-Blind Adjunctive Trials in All indications by Preferred Term at the Recommended Dose of 45 mg/kg/day (Adverse Reactions occurred in at least 1% of BANZEL-treated patients and occurred more frequently than in Placebo Patients)
System Organ Class / Preferred
Term
Placebo
(N=182)
%
BANZEL
(N=187)
%
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation 0 1
Leukopenia 0 1
Neutropenia 0 1
Cardiac disorders
Tachycardia 0 1
Ear and labyrinth disorders
Ear Infection 1 3
Vertigo 0 2
Tinnitus 0 1
Endocrine disorders
Hypothyroidism 0 1
Eye disorders
Diplopia 1 4
Chalazion 0 1
Conjunctival Hyperaemia 0 1
Conjunctivitis Allergic 0 1
Eye Swelling 0 1
Eye Pain0 1
Lacrimation Increased 0 1
Vision Blurred 0 1
Gastrointestinal disorders
Vomiting 7 17
Nausea 3 7
Abdominal Pain Upper 2 3
Abdominal Discomfort 0 1
Faecal Incontinence 0 1
Halitosis 0 1
Gingival Swelling 0 1
Oesophagitis 0 1
Stomach Discomfort 0 1
General disorders and administration site conditions
Fatigue 8 9
Ataxia 1 4
Gait Disturbance 0 2
Difficulty in Walking 0 1
Face Oedema 0 1
Feeling Abnormal 0 1
Injection Site Rash 0 1
Malaise 0 1
Oedema Peripheral 0 1
Immune system disorders
Hypersensitivity 1 2
Infections and infestations
Influenza 4 5
Nasopharyngitis 3 5
Bronchitis 2 3
Sinusitis 2 3
Viral Infection 1 2
Pneumonia 1 2
Pharyngitis Streptococcal 1 2
Cellulitis 0 1
Croup Infectious 0 1
Gingival Abscess 0 1
Hordeolum 0 1
Rubella 0 1
Urinary Tract Infection 0 1
Injury, poisoning and procedural complications
Abdominal Injury 0 1
Arthropod Bite 0 1
Chest Injury 0 1
Foot Fracture 0 1
Injury 0 1
Ligament Injury 0 1
Lower Limb Fracture 0 1
Post Procedural Pain 0 1
Skin Laceration 0 1
Investigations
Weight Decreased 1 2
Hepatic Enzyme Increased 0 1
Respiratory Rate Increased 0 1
Metabolism and nutrition disorders
Decreased Appetite 2 5
Increased Appetite 1 2
Appetite Disorder 0 1
Musculoskeletal and connective tissue disorders
Arthritis 0 1
Back Disorder 0 1
Back Pain 0 1
Buttock Pain 0 1
Neck Pain 0 1
Osteoporosis 0 1
Scoliosis 0 1
Nervous system disorders
Somnolence 9 17
Headache 8 16
Dizziness 6 8
Convulsion 4 5
Disturbance in Attention 1 3
Psychomotor Hyperactivity 1 3
Status Epilepticus 0 2
Aphasia 0 1
Balance Disorder 0 1
Dyskinesia 0 1
Hyperkinesia 0 1
Hypersomnia 0 1
Hypotonia 0 1
Mental Impairment 0 1
Mental Retardation Severity Unspecified0 1
Migraine 0 1
Postictal Headache 0 1
Psychomotor Skills Impaired 0 1
Sciatica 0 1
Speech Disorder 0 1
Tonic Convulsion 0 1
Psychiatric disorders
Aggression 2 3
Depressed Mood 0 1
Disorientation 0 1
Eating Disorder 0 1
Excitability 0 1
Nightmare 0 1
Sleep Disorder 0 1
Renal and urinary disorders
Enuresis 0 1
Urinary Incontinence 0 1
Proteinuria 0 1
Reproductive system and breast disorders
Genital Haemorrhage 0 1
Oligomenorrhoea 0 1
Respiratory, thoracic and mediastinal disorders
Asphyxia 0 1
Bronchospasm 0 1
Dyspnoea 0 1
Increased Bronchial Secretion 01
Productive Cough 0 1
Rhinitis Seasonal 0 1
Skin and subcutaneous tissue disorders
Rash 2 4
Pruritus 0 3
Dermatitis Allergic 0 1
Dermatitis Contact 0 1
Dry Skin 0 1
Eczema 0 1
Exanthem 0 1
Neurodermatitis 0 1
Skin Striae 0 1
Swelling Face 0 1
Urticaria 0 1
Vascular disorders
Hot Flash 0 1
Pallor 0 1
Adults

Table 3 lists treatment-emergent adverse reactions that occurred in at least 1% of adult patients with epilepsy treated with BANZEL (up to 3200 mg/day) in adjunctive controlled studies and were numerically more common in patients treated with BANZEL than placebo. In these studies, either BANZEL or placebo was added to current AED therapy.

Table 3: Incidence (%) of Treatment-Emergent Adverse Reactions in All Adult (≥17 years of age) Double-Blind Adjunctive Trials (up to 3200 mg/day) in All Indications by Preferred Term (Adverse Reactions occurred in at least 1% of BANZEL-treated patients and occurred more frequently than in Placebo Patients)
System Organ Class / Preferred
Term
Placebo
(N=376)
%
BANZEL
(N=823)
%
Ear and labyrinth disorders
Vertigo 1 3
Eye disorders
Diplopia 3 9
Vision Blurred 2 6
Conjunctivitis 0 1
Eye Irritation 0 1
Visual Disturbance 0 1
Gastrointestinal disorders
Nausea 9 12
Vomiting 4 5
Abdominal Pain Upper 2 3
Constipation 2 3
Dyspepsia 2 3
Abdominal Distension 0 1
Loose Stools 0 1
General disorders and administration site conditions
Fatigue 10 16
Gait Disturbance 1 3
Infections and infestations
Bronchitis Acute 0 1
Respiratory Tract Infection 0 1
Injury, poisoning and procedural complications
Face Injury 0 1
Joint Sprain 0 1
Investigations
Weight Decreased 0 1
Metabolism and nutrition disorders
Decreased Appetite 0 1
Musculoskeletal and connective tissue disorders
Back Pain 1 3
Myalgia 0 2
Nervous system disorders
Headache 26 27
Dizziness 12 19
Somnolence 9 11
Nystagmus 5 6
Tremor 5 6
Ataxia 0 4
Balance Disorder 1 2
Cerebellar Syndrome 0 1
Dyskinesia 0 1
Partial Seizures with Secondary Generalization 0 1
Sensory Disturbance 0 1
Speech Disorder 0 1
Status Epilepticus 0 1
Tension Headache 0 1
Psychiatric disorders
Anxiety 2 3
Anorexia 1 2
Nervousness 2 2
Depression 1 2
Apathy 0 1
Skin and subcutaneous tissue disorders
Pruritus 1 2
Skin Lesion 0 1
Vascular disorders
Hypotension 0 1

Discontinuation in Controlled Clinical Studies

Discontinuation Due to Adverse Events in the Controlled Lennox-Gastaut Syndrome Study

In the controlled Lennox Gastaut syndrome study, 8.1% of BANZEL-treated patients and 0% of placebo-treated patients discontinued due to adverse events. The adverse reactions most commonly leading to discontinuation of BANZEL (>1%) are presented in Table 4.

Table 4: Adverse Reactions Most Commonly Leading to Discontinuation in Lennox-Gastaut Syndrome Study in Adult and Pediatric Patients
Preferred
Term
Placebo
(N=64)
%
BANZEL
(N=74)
%
Vomiting 0 4
Rash 0 3
Somnolence 0 3
Anorexia 0 1
Apathy 0 1
Back Disorder 0 1
Convulsions 0 1
Eating Disorder 0 1
Fatigue 0 1
Liver Function Test Abnormal 0 1
Pneumonia 0 1
Discontinuation Due to Adverse Events in All Controlled Clinical Trials in All indications

In controlled double-blind clinical studies, 8.1% of patients receiving BANZEL as adjunctive therapy and 4.3% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (>1%) used as adjunctive therapy were generally similar in adults and children.

Pediatrics

In pediatric double-blind adjunctive clinical studies, 8.0% of patients receiving BANZEL as adjunctive therapy and 2.2% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (>1%) used as adjunctive therapy are presented in Table 5.

Table 5: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials in All Indications (At the Recommended Dose of 45 mg/kg/day) in Pediatric Patients
Preferred
Term
Placebo
(N=182)
%
BANZEL
(N=187)
%
Convulsions 1 2
Rash 1 2
Fatigue 0 2
Vomiting 0 1
Adults

In adult double-blind adjunctive clinical studies (up to 3200 mg/day), 9.5% of patients receiving BANZEL as adjunctive therapy and 5.9% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (>1%) used as adjunctive therapy are presented in Table 6.

Table 6: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials in All Indications (up to 3200 mg/day) in Adult Patients
Preferred
Term
Placebo
(N=376)
%
BANZEL
(N=823)
%
Dizziness 1 2
Fatigue 1 2
Headache 1 2
Ataxia 0 1
Nausea 0 1

Other Adverse Events Observed During Clinical Trials

Adverse events occurring at least three times and considered possibly related to treatment are included in the System Organ Class listings below. Terms not included in the listings are those too general to be informative, those related to procedures and terms describing events common in the population. Some events occurring fewer than 3 times are also included based on their medical significance. Because the reports include events observed in open-label, uncontrolled observations, the role of BANZEL in their causation cannot be reliably determined.

Events are classified by body system and listed in order of decreasing frequency as follows: frequent adverse events- those occurring in at least 1/100 patients; infrequent adverse events- those occurring in 1/100 to 1/1000 patients; rare- those occurring in fewer than 1/1000 patients.

Blood and Lymphatic System Disorders: Frequent: anemia. Infrequent: lymphadenopathy, leukopenia, neutropenia, iron deficiency anemia, thrombocytopenia.

Cardiac Disorders: Infrequent: bundle branch block right, atrioventricular block first degree.

Metabolic and Nutritional Disorders: Frequent: decreased appetite, increased appetite.

Renal and Urinary Disorders: Frequent: pollakiuria. Infrequent: urinary incontinence, dysuria, hematuria, nephrolithiasis, polyuria, enuresis, nocturia, incontinence.

Abnormal Hematologic and Clinical Chemistry Findings

Leukopenia (white cell count <3x109 L) was more commonly observed in BANZEL-treated patients (43 of 1171, 4%) than placebo-treated patients (7 of 579, 1%) in all controlled trials.

Long-term Safety in Lennox-Gastaut Syndrome

Pediatrics and Adults (between 4 and 37 years of age):

In a 36-month observational open label study, 124 patients were treated with rufinamide; 71.8% were between 4 and 16 years of age. The median daily dose of rufinamide during therapy was 1800 mg/day ranging from 103 to 4865 mg/day. The median duration of exposure to rufinamide was 432 days (range 10-1149 days). Thirty-four percent of patients completed the study. Twelve patients (9.7%) discontinued due to adverse events. The four most frequent adverse events observed during rufinamide treatment were vomiting (31%), pyrexia (26%), upper respiratory tract infection (22%) and somnolence (21%). The long-term safety profile was similar to that found in the 12-week, controlled portion of study.

Post-Market Adverse Drug Reactions

The following serious and unexpected adverse reactions have been identified in patients receiving marketed BANZEL from worldwide use since approval. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The adverse drug reactions are ranked by frequency, calculated per patient-years of estimated exposure.

Table 7: Post-market Reports of Adverse Drug Reactions
Serious Adverse Event Frequency
Common
≥1%
Uncommon
<1% and
≥0.1%
Rare
<0.1% and≥
0.01%
Very Rare
<0.01%
Blood and lymphatic system disorders
Thrombocytopenia
Cardiac disorders
Myocardial infarction
Eye disorders
Eye movement disorder1
Gastrointestinal disorders
Diarrhoea
Pancreatitis
Pancreatis acute
General disorders and administration site conditions
Asthenia
Death
Drug intolerance
Fatigue2
Irritability
Pain
Pyrexia3
Sudden unexplained death in epilepsy
Hepatobiliary disorders
Cholelithiasis
Hepatic failure
Hepatitis cholestatic
Infections and infestations
Bronchopneumonia
Injury, poisoning and procedural complications
Fall
Rib Fracture
Tooth injury
Upper limb fracture
Investigations
Electrocardiogram QT shortened4
Eosinophil count increased3
Haemoglobin decreased
Liver function test abnormal3
Platelet count decreased
Quality of life decreased
Weight decreased
Metabolism and nutrition disorders
Appetite disorder
Hypoglycaemia
Lactic acidosis
Metabolic acidosis
Musculoskeletal and connective tissue disorders
Muscular weakness
Nervous system disorders
Aphasia
Ataxia5
Convulsion
Coordination Abnormal
Drooling
Dyskinesia
Encephalopathy
Lethargy
Speech disorder
Status epilepticus6
Psychiatric disorders
Abnormal behaviour
Aggression
Agitation
Conduct disorder
Depression
Dyssomnia
Hallucination
Obsessive-compulsive disorder
Paranoia
Psychotic disorder
Suicidal behaviour7
Suicidal ideation7
Renal and urinary disorders
Renal failure
Renal failure acute
Reproductive system and breast disorders
Menometrorrhagia
Skin and subcutaneous tissue disorders
Alopecia
Hair colour changes
Hyperhidrosis
Rash3
Stevens-Johnson syndrome
Trichorrhexis
Vascular disorders
Hyperaemia
Thrombosis

1see WARNINGS AND PRECAUTIONS, Ophthalmological Effects

2see WARNINGS AND PRECAUTIONS, Neurologic, Somnolence and Fatigue, see DRUG INTERACTIONS, Drug-Lifestyle Interactions

3see WARNINGS AND PRECAUTIONS, Sensitivity/Resistance

4see WARNINGS AND PRECAUTIONS, Cardiovascular

5see WARNINGS AND PRECAUTIONS, Neurologic, Dizziness and Ataxia, see DRUG INTERATIONS, Drug-Lifestyle Interactions

6see WARNINGS AND PRECAUTIONS, Neurologic, Status Epilepticus

7see WARNINGS AND PRECAUTIONS, Psychiatric

Drug Interactions

Overview

In vitro and in vivo studies have shown that BANZEL is unlikely to be involved in significant pharmacokinetic interaction.

Based on in vitro studies, rufinamide shows little or no inhibition of most cytochrome P450 enzymes at clinically relevant concentrations, with weak inhibition of CYP 2E1. Drugs that are substrates of CYP 2E1 (e.g., chlorzoxazone) may have increased plasma levels in the presence of rufinamide, but this has not been studied.

Based on in vivo drug interaction studies with triazolam and oral contraceptives, rufinamide is a weak inducer of the CYP 3A4 enzyme and can decrease exposure of drugs that are substrates of CYP 3A4 (see Effects of BANZEL on Other Medications).

Rufinamide is metabolized by carboxylesterases. Drugs that may induce the activity of carboxylesterases may increase the clearance of rufinamide. Broad-spectrum inducers such as carbamazepine and phenobarbital may have minor effects on rufinamide metabolism via this mechanism. Drugs that are inhibitors of carboxylesterases may decrease metabolism of rufinamide. See Table 8.

As with all centrally acting medications, alcohol in combination with BANZEL may cause additive central nervous system effects.

Drug-Drug Interactions

Antiepileptic Drugs

Effects of Banzel on Other AEDs

Population pharmacokinetic analysis of average concentration at steady state, of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, and valproate showed that typical rufinamide Cavss levels had little effect on the pharmacokinetics of other AEDs. Any effects, when they occurred, have been more marked in the pediatric population.

Phenytoin:

The decrease in clearance of phenytoin estimated at typical levels of rufinamide (Cavss 15 µg/mL) is predicted to increase plasma levels of phenytoin by 7 to 21%. As phenytoin is known to have non-linear pharmacokinetics (clearance becomes saturated at higher doses), it is possible that exposure will be greater than the model prediction, particularly at higher doses.

Table 8 summarizes the drug-drug interactions of BANZEL with other AEDs.

Table 8: Summary of Drug-Drug Interactions of BANZEL with Other Antiepileptic Drugs
AED
Co-administered
Influence of Rufinamide on AED concentrationa) Influence of AED on Rufinamide concentration
Carbamazepine Decrease by 7 to 13%b) Decrease by 19 to 26%
Dependent on dose of carbamazepine
Lamotrigine Decrease by 7 to 13%b) No Effect
Phenobarbital Increase by 8 to 13%b) Decrease by 25 to 46%c), d)
Independent of dose or concentration of phenobarbital
Phenytoin Increase by 7 to 21%b) Decrease by 25 to 46%c), d)
Independent of dose or concentration of phenytoin
Topiramate No Effect No Effect
Valproate No Effect Increase by <16 to 70% c)
Dependent on concentration of valproate
Primidone Not Investigated Decrease by 25 to 46%c), d)
Independent of dose or concentration of primidone
Benzodiazepines e) Not Investigated No Effect

a) Predictions are based on BANZEL concentrations at the maximum recommended dose of BANZEL.

b) Maximum changes predicted to be in children and in patients who achieve significantly higher levels of BANZEL, as the effect of rufinamide on these AEDs is concentration-dependent.

c) Larger effects in children at high doses/concentrations of AEDs.

d) Phenobarbital, primidone and phenytoin were treated as a single covariate (phenobarbital-type inducers) to examine the effect of these agents on BANZEL clearance.

e) All compounds of the benzodiazepine class were pooled to examine for ‘class effect’ on BANZEL clearance.

Effects of Other AEDs on Banzel
Valproate:

Depending on its dose, valproate can increase plasma concentration of BANZEL by up to 70%. Therefore, patients stabilized on BANZEL before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose. Similarly, depending on their weight, patients on valproate therapy should begin at a BANZEL dose lower than the recommended daily starting dose.

Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital appear to increase the clearance of BANZEL (see Table 8). Given that the majority of clearance of BANZEL is via a non-CYP-dependent route, the observed decreases in blood levels seen with carbamazepine, phenytoin, phenobarbital, and primidone are unlikely to be entirely attributable to induction of a P450 enzyme. Other factors explaining this interaction are not understood. Any effects, where they occurred were likely to be more marked in the pediatric population.

Effects of Banzel on Other Medications
Hormonal Contraceptives:

Coadministration of BANZEL (800 mg b.i.d for 14 days) with ethinyl estradiol and norethindrone can decrease AUC0-24 of these hormonal contraceptives by 22% and 14% and Cmax by 31% and 18%, respectively. Female patients of childbearing age should be warned that the concurrent use of BANZEL with hormonal contraceptives may render this method of contraception less effective. Additional non-hormonal forms of contraception are recommended when using BANZEL.

Triazolam:

Co-administration and pre-treatment with BANZEL (400 mg b.i.d) in healthy volunteers (n = 21) resulted in a 37% decrease in AUC and a 23% decrease in Cmax of triazolam, a CYP 3A4 substrate.

Olanzapine:

Co-administration and pre-treatment with BANZEL (400 mg b.i.d) in healthy volunteers (n = 19) resulted in no change in AUC and Cmax of olanzapine, a CYP 1A2 substrate.

Drug-Food Interactions

Food increased the extent of absorption and peak exposure of rufinamide in healthy volunteers after a single dose of 400 mg, although the Tmax was not increased. Clinical trials were performed under fed conditions and dosing is recommended with food (see DOSAGE AND ADMINISTRATION).

Drug-Laboratory Test Interactions

There are no known interactions of BANZEL with commonly used laboratory tests.

Drug-Lifestyle Interactions

Patients should be advised about the potential for somnolence or dizziness and advised not to drive or operate machinery until they have gained sufficient experience on BANZEL to gauge whether it adversely affects their mental and/or motor performance.

Dosage and Administration

Dosing Considerations

BANZEL should be given with food. Absence of food may reduce bioavailability.

Patients with Renal Impairment

Renally impaired patients (creatinine clearance less than 30 mL/min) do not require any special dosage change when taking BANZEL.

Patients Undergoing Hemodialysis

Hemodialysis may reduce exposure to a limited extent (about 30%). Accordingly, adjusting the BANZEL dose during the dialysis process may be considered (see WARNINGS AND PRECAUTIONS and ACTION AND CLINICAL PHARMACOLOGY).

Patients with Hepatic Disease

Use of BANZEL in patients with hepatic impairment has not been studied. Therefore, use in patients with severe hepatic impairment is not recommended. Caution should be exercised in treating patients with mild to moderate hepatic impairment.

Recommended Dose and Dosage Adjustment

Use in children and adults less than 30 kg

Treatment should be initiated at a daily dose of 200 mg administered in two equally divided doses. According to clinical response and tolerability, the dose should be increased at 5 mg/kg/day every two weeks, after an evaluation of efficacy. Titration should be stopped after a satisfactory control of seizures is obtained. Maximum recommended daily dose in this population is 1300 mg/day.

Use in adults and children 30 kg or over

Treatment should be initiated at a daily dose of 400 mg administered in two equally divided doses. According to clinical response and tolerability, the dose should be increased at 5 mg/kg/day every two weeks, after an evaluation of efficacy. Titration should be stopped after a satisfactory control of seizures is obtained. In clinical trials, the dose was increased as frequently as every two days.

Weight range 30.0 - 50.0 kg 50.1 - 70.0 kg ≥70.1 kg
Maximum recommended dose (mg/day) 1800 2400 3200

Safety of doses above 3200 mg/day has not been established.

Valproate:

Depending on its dose, valproate can increase plasma concentration of BANZEL by up to 70% (see DRUG INTERACTIONS). Therefore, patients stabilized on BANZEL before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose. Similarly, depending on their weight, patients on valproate therapy should begin at a BANZEL dose lower than the recommended daily starting dose.

Missed Dose

A missed dose should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule followed. The dose should not be doubled to make up for a missed dose.

Administration

BANZEL tablets are scored on both sides and can be cut in half for dosing flexibility. Tablets can be administered whole, as half tablets or crushed.

Overdosage

One overdose of 7200 mg/day BANZEL was reported in an adult during the clinical trials. The overdose was associated with no major signs or symptoms, no medical intervention was required, and the patient continued in the study at the target dose.

Treatment or Management of Overdose: There is no specific antidote for overdose with BANZEL. If clinically indicated, elimination of unabsorbed drug should be attempted by induction of emesis or gastric lavage. Usual precautions should be observed to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient.

Hemodialysis: Standard hemodialysis procedures may result in limited clearance of rufinamide. Although there is no experience to date in treating overdose with hemodialysis, the procedure may be considered when indicated by the patient′s clinical state.

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Action and Clinical Pharmacology

Mechanism of Action

The precise mechanism(s) by which rufinamide exerts its antiepileptic effect in humans, is unknown.

Pharmacodynamics

Population pharmacokinetic/pharmacodynamic modelling demonstrated that in the Lennox-Gastaut trial, the reduction of total and tonic-clonic seizure frequencies, the improvement of the global evaluation of seizure severity and rate of reduction of seizure frequency by >50% were dependent on rufinamide concentrations. Linear relationships were estimated between average rufinamide concentrations at steady-state (or log Cavss) and: the natural logarithm of seizure frequency, the severity rating score, and the logit of probability of response. None of these relationships were affected by concomitant administration of the AEDs studied which included valproate, lamotrigine, topiramate and clonazepam.

A study in healthy volunteers of the effect of rufinamide at a single oral dose of 800 mg on acoustically evoked potential found a statistically significant (p<0.05) increase of the N100 amplitude with rufinamide compared to placebo. As the N100 likely reflects early attentional and orienting processes, the increase in N100 suggests an intensified attentional focusing on target stimuli. No rufinamide related effects were found on contingent negative variation, monitoring anticipation and behavioural control, and on mean reaction time. Rufinamide also

had no influence on the spontaneous-EEG parameters α-power and centre frequency. Rufinamide did not change hyperventilation-related negative DC-shift suggesting the lack of general depressant effects of rufinamide.

Pharmacokinetics

Absorption:

Rufinamide is well absorbed. Following oral administration of BANZEL, peak plasma concentrations occur between 4 and 6 hours (Tmax ) both under fed and fasted conditions. BANZEL tablets display decreasing bioavailability with increasing dose after single and multiple dose administration. At doses lower than 400 mg, the exposure increases approximately proportionally to the dose. Based on urinary excretion, the extent of absorption was at least 85% following oral administration of a single dose of 600 mg rufinamide under fed conditions.

Food increased the extent of absorption of rufinamide in healthy volunteers by 34% and increased peak exposure by 56% after a single dose of 400 mg, although the Tmax was not elevated. Clinical trials were performed under fed conditions and dosing is recommended with food (see DOSAGE AND ADMINISTRATION).

Upon multiple dosing b.i.d, steady-state is reached in 2-3 days. The elimination half

Distribution:

Only a small fraction of rufinamide (34%) is bound to human serum proteins, predominantly to albumin (27%), giving little risk of displacement drug-drug interactions. Rufinamide was evenly distributed between erythrocytes and plasma. The apparent volume of distribution is dependent upon dose and varies with body surface area. The apparent volume of distribution was about 50 L at 3200 mg/day.

The clearance and volume of distribution of rufinamide increase with body surface area. Clearance is not affected by renal or liver function markers or by the age or gender of the patient.

Typical pharmacokinetic parameters after multiple 1600 mg b.i.d doses of rufinamide in healthy adult volunteers under fed conditions are shown in Table 9.

Table 9: Summary of Rufinamide Pharmacokinetic Parameters in Healthy Adult Volunteers
Dose Cmax
(µg/mL)
Tmax
(h)
AUC0-12
(h.µg/mL)
Apparent Clearance (CL/F)
(L/h)
1600 mg b.i.d 22.52
(19.67; 26.69)
4.00
(3.00; 4.07)
225
(197; 264)
7.11

In patients with epilepsy, rufinamide exposure predicted from a population PK model in populations of children (<11 years), adolescents (12-17 years) and adults administered doses of 41 to 50 mg/kg body weight are presented in Table 10. The exposure appears to be lower than in healthy subjects treated with comparable doses (3200 mg/day).

Table 10: Exposure in Patients with Epilepsy Treated with BANZEL 41-50 mg/kg/day
Age Group Cavss (µg/mL) AUC24SS (h.µg/mL)
>2 to <12 years 12.63 (11.87; 13.44) 303.1 (284.85; 322.52)
≥12 to <18 years 13.23 (12.6; 13.9) 317.63 (302.47; 333.56)
≥18 years 12.68 (12.18; 13.2) 304.27 (292.33; 316.7)

Metabolism:

Rufinamide is extensively metabolized by hydrolysis of the carboxide group to the carboxylic acid derivative (CGP 47292). This metabolite, which is pharmacologically inactive, is mainly cleared by renal excretion. A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. There is no evidence of oxidative metabolism by cytochrome P450 enzymes, or of conjugation with glutathione. Following a radiolabeled dose of rufinamide, less than 2% of the dose is excreted unchanged in the urine.

Rufinamide is a weak inhibitor of CYP 2E1. It did not show significant inhibition of other CYP enzymes. Rufinamide is a weak inducer of CYP 3A4 enzymes.

Excretion:

Renal excretion is the predominant route of elimination for drug related material, accounting for 85% of the dose based on a radiolabeled study. Of the metabolites identified in urine, at least 66% of the rufinamide dose was excreted as the acid metabolite CGP 47292, with 2% of the dose excreted as rufinamide.

The plasma elimination half-life is approximately 6-10 hours in healthy subjects and patients with epilepsy.

Special Populations and Conditions

Pediatrics:

Based on a population analysis in 117 children (age 4-11 years) and 99 adolescents (age 12-17 years), the pharmacokinetics of rufinamide in these patients is similar to the pharmacokinetics in adults.

Geriatrics:

The results of a study evaluating single-dose (400 mg) and multiple dose (800 mg/day for 6 days) pharmacokinetics of rufinamide in 8 healthy elderly subjects (65-80 years old) and 7 younger healthy subjects (18-45 years old) found no significant age-related differences in the pharmacokinetics of rufinamide.

Gender:

Population pharmacokinetic analyses of females show a 6-14% lower apparent clearance of rufinamide compared to males. This effect is not clinically important.

Race:

In a population pharmacokinetic analysis of clinical studies, no difference in clearance or volume of distribution of rufinamide was observed between the Black (n = 32) and Caucasian (n = 481) subjects, after controlling for body size. Information on other races could not be obtained because of smaller numbers of these subjects.

Hepatic Insufficiency:

There have been no specific studies investigating the effect of hepatic impairment on the pharmacokinetics of rufinamide.

Renal Insufficiency:

Rufinamide pharmacokinetics in 9 patients (7 males, 2 females), age range from 32 to 61 years, with severe renal impairment (creatinine clearance <30 mL/min) was similar to that of 9 healthy subjects (29 to 63 years). Patients undergoing dialysis 3 hours after rufinamide dosing showed a reduction in AUC and Cmax by 29% and 16%, respectively. Adjusting rufinamide dose for the loss of drug upon dialysis may be considered (see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Storage and Stability

Tablets

Store at room temperature (15°-30°C). Protect from moisture.

Replace cap securely after opening.

Keep in a safe place out of the reach of children.

Dosage Forms, Composition and Packaging

Tablets

BANZEL is available for oral administration in film-coated tablets, scored on both sides, containing 100 mg, 200 mg and 400 mg of rufinamide. Non-medicinal ingredients are colloidal silicon dioxide, corn starch, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulphate. The film coating contains hypromellose, iron oxide red, polyethylene glycol, talc and titanium dioxide.

BANZEL 100 mg tablets (containing 100 mg rufinamide) are pink in color, film-coated, ovaloid shaped tablets, slightly convex faces, with a score on both sides, imprinted with “Є261” on one side. They are available in bottles of 30.

BANZEL 200 mg tablets (containing 200 mg rufinamide) are pink in color, film-coated, ovaloid shaped tablets, slightly convex faces, with a score on both sides, imprinted with “Є262” on one side. They are available in bottles of 30 and 120.

BANZEL 400 mg tablets (containing 400 mg rufinamide) are pink in color, film-coated, ovaloid shaped tablets, slightly convex faces, with a score on both sides, imprinted with “Є263” on one side. They are available in bottles of 120.