1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Adult and Pediatric Patients ages 3 to 17 years of age In the pooled, double-blind, adjunctive therapy studies in adult and pediatric patients ages 3 to 17 years of age, the most common (≥10%) adverse reactions in BANZEL-treated patients, in all doses studied (200 to 3200 mg per day) with a higher frequency than in patients on placebo were: headache, dizziness, fatigue, somnolence, and nausea.
Table 2 lists adverse reactions that occurred in at least 3% of pediatric patients (ages 3 to less than 17 years) with epilepsy treated with BANZEL in controlled adjunctive studies and were numerically more common in patients treated with BANZEL than in patients on placebo.
At the target dose of 45 mg/kg per day for adjunctive therapy in pediatric patients (ages 3 to less than 17 years), the most common (≥3%) adverse reactions with an incidence greater than in placebo for BANZEL were somnolence, vomiting, and headache.
Table 2:
Adverse Reactions in Pediatric Patients (Ages 3 to less than 17 years) in Pooled Double-Blind Adjunctive Trials Adverse Reaction BANZEL (N=187) % Placebo (N=182) % Somnolence 17 9 Vomiting 17 7 Headache 16 8 Fatigue 9 8 Dizziness 8 6 Nausea 7 3 Influenza 5 4 Nasopharyngitis 5 3 Decreased Appetite 5 2 Rash 4 2 Ataxia 4 1 Diplopia 4 1 Bronchitis 3 2 Sinusitis 3 2 Psychomotor Hyperactivity 3 1 Upper Abdominal Pain 3 2 Aggression 3 2 Ear Infection 3 1 Disturbance in Attention 3 1 Pruritis 3 0 Table 3 lists adverse reactions that occurred in at least 3% of adult patients with epilepsy treated with BANZEL (up to 3200 mg per day) in adjunctive controlled studies and were numerically more common in patients treated with BANZEL than in patients on placebo.
In these studies, either BANZEL or placebo was added to the current AED therapy. At all doses studied of up to 3200 mg per day given as adjunctive therapy in adults, the most common (≥ 3%) adverse reactions, and with the greatest increase in incidence compared to placebo, for BANZEL were dizziness, fatigue, nausea, diplopia, vision blurred, and ataxia.
Table 3:
Adverse Reactions in Adults in Pooled Double-Blind Adjunctive Trials Adverse Reaction BANZEL (N=823) % Placebo (N=376) % Headache 27 26 Dizziness 19 12 Fatigue 16 10 Nausea 12 9 Somnolence 11 9 Diplopia 9 3 Tremor 6 5 Nystagmus 6 5 Blurred Vision 6 2 Vomiting 5 4 Ataxia 4 0 Upper Abdominal Pain 3 2 Anxiety 3 2 Constipation 3 2 Dyspepsia 3 2 Back Pain 3 1 Gait Disturbance 3 1 Vertigo 3 1 Discontinuation in Controlled Clinical Studies In controlled, double-blind, adjunctive clinical studies, 9% of pediatric and adult patients receiving BANZEL as adjunctive therapy and 4% 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 pediatric patients. In pediatric patients (ages 4 to less than 17 years) double-blind adjunctive clinical studies, 8% of patients receiving BANZEL as adjunctive therapy (at the recommended dose of 45 mg/kg per day) and 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 4.
Table 4:
Most Common Adverse Reactions Leading to Discontinuation in Pediatric Patients (Ages 4 to less than 17 years) in Pooled Double-Blind Adjunctive Trials Adverse Reaction BANZEL (N=187) % Placebo (N=182) % Convulsion 2 1 Rash 2 1 Fatigue 2 0 Vomiting 1 0 In adult double-blind, adjunctive clinical studies, 10% of patients receiving BANZEL as adjunctive therapy (at doses up to 3200 mg per day) and 6% 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:
Most Common Adverse Reactions Leading to Discontinuation in Adult Patients in Pooled Double-Blind Adjunctive Trials Adverse Reaction BANZEL (N=823) % Placebo (N=376) % Dizziness 3 1 Fatigue 2 1 Headache 2 1 Nausea 1 0 Ataxia 1 0 Pediatric Patients age s 1 to less than 4 years In a multicenter, parallel group, open-label study comparing BANZEL (45 mg/kg per day) adjunctive treatment (n=25) to the adjunctive treatment with an AED of the investigator’s choice (n=11) in pediatric patients (1 year to less than 4 years of age) with inadequately controlled Lennox-Gastaut Syndrome, the adverse reaction profile was generally similar to that observed in adults and pediatric patients 4 years of age and older treated with BANZEL.
Adverse reactions that occurred in at least 2 (8%) BANZEL-treated patients and with a higher frequency than in the AED comparator group were: vomiting (24%), somnolence (16%), bronchitis (12%), constipation (12%), cough (12%), decreased appetite (12%), rash (12%), otitis media (8%), pneumonia (8%), decreased weight (8%), gastroenteritis (8%), nasal congestion (8%), and pneumonia aspiration (8%).
Other Adverse Reactions Observed During Clinical Trials BANZEL has been administered to 1978 individuals during all epilepsy clinical trials (placebo-controlled and open-label). Adverse reactions occurring during these studies were recorded by the investigators using terminology of their own choosing.
To provide a meaningful estimate of the proportion of patients having adverse reactions, these events were grouped into standardized categories using the MedDRA dictionary. 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 already included in the tables above, 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. 2 Post m arketing Experience The following adverse reactions have been identified during post approval use of BANZEL.
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.
Dermatologic:
Stevens-Johnson syndrome and other serious skin rashes with mucosal involvement.