英文药名：BANZEL（rufinamide tablets/ oral suspension） 中文药名：卢非酰胺片/口服混悬液 生产厂家：卫材公司 药品介绍 美国食品和药物管理局FDA已经批准BANZE（卢非酰胺Rufinamide）作为辅助治疗1-4岁小儿患者Lennox-Gastaut综合症（LGS）相关的癫痫发作。 BANZEL最早是在2008年11月被FDA批准，用于辅助治疗4岁以上的儿童，老年人和成年人LGS相关的癫痫发作。 BANZEL作为辅助治疗伦Lennox-Gastaut综合征（LGS）在1-4岁小儿患者的癫痫发作相关的批准是基于III期临床试验的药代动力学研究（研究303），它体现了药代动力学和安全数据与4岁以上年龄中的表现相一致。 BANZEL（卢非酰胺Rufinamide）是一种抗癫痫药物，用于辅助治疗Lennox-Gastaut综合征（LGS）一岁以上患者的相关癫痫发作。 BANZEL是三唑衍生物,结构上与目前市售的抗癫痫药无相似性。这种结构差异的临床机理尚未确立，据信通过调节钠例子通道，避免其脑携带过多电从而可能引起癫痫发作的活性，从而发挥其抗癫痫作用。 BANZEL目前上市剂型为200和400mg片剂与40mg/ml口服悬浊液，自2008年11月14日获FDA批准上市 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BANZEL ® safely and effectively. See full prescribing information for BANZEL ® . BANZEL ® (rufinamide) film-coated tablet, for o ral u se BANZEL ® (rufinamide) oral suspension Initial U.S. Approval: 2008 RECENT MAJOR CHANGES Indications and Usage (1)       02/2015 INDICATIONS AND USAGE BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults (1) DOSAGE AND ADMINISTRATION BANZEL should be given with food. Tablets can be administered whole, as half tablets, or crushed (2.2) Measure oral suspension using provided adapter and dosing syringe (2.2) Pediatric patients 1 year and older:  Starting daily dose: 10 mg/kg per day in two equally divided doses (2.1) Increase by 10 mg/kg increments every other day to maximum dose of 45 mg/kg per day, not to exceed 3200 mg per day, in two divided doses (2.1) Adults:  Starting daily dose: 400-800 mg per day in two equally divided doses (2.1) Increase by 400-800 mg every other day until a maximum dose of 3200 mg per day, in two divided doses, is reached (2.1) DOSAGE FORMS AND STRENGTHS Film-coated tablets: 200 mg (pink), 400 mg (pink) (3) Oral suspension: 40 mg/mL (3) CONTRAINDICATIONS BANZEL is contraindicated in patients with Familial Short QT syndrome (4) WARNINGS AND PRECAUTIONS Monitor patients for new or worsening depression, suicidal thoughts/behavior, and unusual changes in mood or behavior (5.1) Central nervous system reactions can occur (5.2) Use caution when administering BANZEL with other drugs that shorten the QT interval (5.3) Discontinue BANZEL if multi-organ hypersensitivity reaction occurs (5.4) Withdraw BANZEL gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus (5.5) ADVERSE REACTIONS Most common adverse reactions (≥ 10% and greater than placebo) were headache, dizziness, fatigue, somnolence, and nausea (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Eisai, Inc. at 1-888-274-2378 or www.banzel.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Patients on valproate should begin at a BANZEL dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults) (7.2) Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception (7.3) USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. (8.1) Renal impairment: Consider adjusting the BANZEL dose for the loss of drug upon dialysis (8.6) Not recommended in patients with severe hepatic impairment (8.7) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 6/2015 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults. 2 DOSAGE AND ADMINISTRATION 2.1 Dosage Information Pediatric patients (1 year to less than 17 years)  The recommended starting daily dose of BANZEL in pediatric patients with Lennox-Gastaut Syndrome is approximately 10 mg/kg administered in two equally divided doses. The dose should be increased by approximately 10 mg/kg increments every other day until a maximum daily dose of 45 mg/kg, not to exceed 3200 mg, administered in two equally divided doses, is reached. It is not known whether doses lower than the target doses are effective. Adults (17 years and older) The recommended starting daily dose of BANZEL in adults with Lennox-Gastaut Syndrome is 400 to 800 mg per day administered in two equally divided doses. The dose should be increased by 400-800 mg every other day until a maximum daily dose of 3200 mg, administered in two equally divided doses, is reached. It is not known whether doses lower than 3200 mg are effective. 2.2 Administration Information Administer BANZEL with food. BANZEL film-coated tablets can be administered whole, as half tablets or crushed. BANZEL oral suspension should be shaken well before every administration. The provided adapter and calibrated oral dosing syringe should be used to administer the oral suspension. The adapter which is supplied in the product carton should be inserted firmly into the neck of the bottle before use and remain in place for the duration of the usage of the bottle. The dosing syringe should be inserted into the adapter and the dose withdrawn from the inverted bottle. The cap should be replaced after each use. The cap fits properly when the adapter is in place [see Patient Counseling Information (17)]. 2.3 Dosing in Patients Undergoing Hemodialysis Hemodialysis may reduce exposure to a limited (about 30%) extent. Accordingly, adjusting the BANZEL dose during the dialysis process should be considered [see Clinical Pharmacology (12.3)]. 2.4 Dosing in 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 [see Use in Specific Populations (8.7)]. 2.5 Dosing in Patients Taking Valproate Patients taking valproate should begin BANZEL at a dose lower than 10 mg/kg per day in pediatric patients or 400 mg per day in adults [see Drug Interactions (7.2)].  3 DOSAGE FORMS AND STRENGTHS Film-coated Tablets: 200 mg (pink) and 400 mg (pink). Tablets are scored on both sides. Oral Suspension: 40 mg/mL. 4  CONTRAINDICATIONS BANZEL is contraindicated in patients with Familial Short QT syndrome [see Warnings and Precautions (5.3)]. 5 WARNINGS AND PRECAUTIONS 5.1  Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including BANZEL, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1: Absolute and Relative Risk of Suicidal Behavior and Ideation Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing BANZEL or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. 5.2  Central Nervous System Reactions Use of BANZEL has been associated with central nervous system-related adverse reactions in the controlled clinical trial of patients 4 years or older with Lennox-Gastaut Syndrome. The most significant of these can be classified into two general categories: 1) somnolence or fatigue, and 2) coordination abnormalities, dizziness, gait disturbances, and ataxia. Somnolence was reported in 24% of BANZEL-treated patients compared to 13% of patients on placebo, and led to study discontinuation in 3% of BANZEL-treated patients compared to 0% of patients on placebo. Fatigue was reported in 10% of BANZEL-treated patients compared to 8% of patients on placebo patients. It led to study discontinuation in 1% of BANZEL-treated patients and 0% of patients on placebo patients. Dizziness was reported in 2.7% of BANZEL-treated patients compared to 0% of patients on placebo, and did not lead to study discontinuation. Ataxia and gait disturbance were reported in 5.4% and 1.4% of BANZEL-treated patients, respectively, compared to no patient on placebo. None of these reactions led to study discontinuation. Accordingly, patients should be advised not to drive or operate machinery until they have gained sufficient experience on BANZEL to gauge whether it adversely affects their ability to drive or operate machinery. 5.3 QT Shortening Formal cardiac ECG studies demonstrated shortening of the QT interval (mean = 20 msec, for doses >2400 mg twice daily) with BANZEL. In a placebo-controlled study of the QT interval, 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%). Reductions of the QT interval below 300 msec were not observed in the formal QT studies with doses up to 7200 mg per day. Moreover, there was no signal for drug-induced sudden death or ventricular arrhythmias. 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. Non-clinical data also indicate that QT shortening is associated with ventricular fibrillation. Patients with Familial Short QT syndrome should not be treated with BANZEL. Caution should be used when administering BANZEL with other drugs that shorten the QT interval [see Contraindications (4)].  5.4 Multi-organ Hypersensitivity/Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has been reported in patients taking antiepileptic drugs, including BANZEL.  DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.  Because this disorder is variable in its expression, other organ systems not noted here may be involved. All cases of DRESS identified in clinical trials with BANZEL occurred in pediatric patients less than 12 years of age, occurred within 4 weeks of treatment initiation, and resolved or improved with BANZEL discontinuation. DRESS has also been reported in adult and pediatric patients taking BANZEL in the postmarketing setting. If DRESS is suspected, the patient should be evaluated immediately, BANZEL should be discontinued, and alternative treatment should be started. 5.5 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 2 days. 5.6 Status Epilepticus Estimates of the incidence of treatment emergent status epilepticus among patients treated with BANZEL are difficult because standard definitions were not employed. In a controlled Lennox-Gastaut Syndrome trial, 3 of 74 (4.1%) BANZEL-treated patients had episodes that could be described as status epilepticus in the BANZEL-treated patients compared with none of the 64 patients in the placebo-treated patients. In all controlled trials that included patients with different epilepsies, 11 of 1240 (0.9%) BANZEL-treated patients had episodes that could be described as status epilepticus compared with none of 635 patients in the placebo-treated patients. 5.7 Leukopenia BANZEL has been shown to reduce white cell count. Leukopenia (white cell count < 3X109 L) was more commonly observed in BANZEL-treated patients 43 of 1171 (3.7%) than placebo-treated patients, 7 of 579 (1.2%) in all controlled trials. 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)] Central Nervous System Reactions [see Warnings and Precautions (5.2)] QT Shortening [see Warnings and Precautions (5.3)] Multi-Organ Hypersensitivity/Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)] Leukopenia [see Warnings and Precautions (5.7)] 6.1 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 ages 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. 6.2 Postmarketing 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. 7 DRUG INTERACTIONS 7.1 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 occur, have been more marked in the pediatric population. Table 6 summarizes the drug-drug interactions of BANZEL with other AEDs. Table 6: 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 pediatric patients and in adult patients who achieve significantly higher levels of BANZEL, as the effect of rufinamide on these AEDs is concentration-dependent. c) Larger effects in pediatric patients 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. 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. 7.2  Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). 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. Valproate Patients stabilized on BANZEL before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose. Similarly, patients on valproate should begin at a BANZEL dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults) [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]. 7.3  Effects of BANZEL on Hormonal Contraceptives 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 [see Clinical Pharmacology (12.3) and Patient Counseling Information (17)]. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. BANZEL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Rufinamide produced developmental toxicity when administered orally to pregnant animals at clinically relevant doses. Rufinamide was administered orally to rats at doses of 20, 100, and 300 mg/kg per day and to rabbits at doses of 30, 200, and 1000 mg/kg/day during the period of organogenesis (implantation to closure of the hard palate); the high doses are associated with plasma AUCs ≈2 times the human plasma AUC at the maximum recommended human dose (MRHD, 3200 mg per day). Decreased fetal weights and increased incidences of fetal skeletal abnormalities were observed in rats at doses associated with maternal toxicity. In rabbits, embryo-fetal death, decreased fetal body weights, and increased incidences of fetal visceral and skeletal abnormalities occurred at all but the low dose. The highest dose tested in rabbits was associated with abortion. The no-effect doses for adverse effects on rat and rabbit embryo-fetal development (20 and 30 mg/kg per day, respectively) were associated with plasma AUCs ≈ 0.2 times that in humans at the MRHD. In a rat pre- and post-natal development study (dosing from implantation through weaning) conducted at oral doses of 5, 30, and 150 mg/kg per day (associated with plasma AUCs up to ≈1.5 times that in humans at the MRHD), decreased offspring growth and survival were observed at all doses tested. A no-effect dose for adverse effects on pre- and post-natal development was not established. The lowest dose tested was associated with plasma AUC < 0.1 times that in humans at the MRHD. Pregnancy Registry To provide information regarding the effects of in utero exposure to BANZEL, 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 website http://www.aedpregnancyregistry.org/. 8.3 Nursing Mothers Rufinamide is likely to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from BANZEL, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness have been established in pediatric patients 1 to 17 years of age. The effectiveness of BANZEL in pediatric patients 4 years of age and older was based upon an adequate and well-controlled trial of BANZEL that included both adults and pediatric patients, 4 years of age and older, with Lennox Gastaut Syndrome. The effectiveness in patients 1 to less than 4 years was based upon a bridging pharmacokinetic and safety study [see Dosage and Administration (2.1), Adverse Reactions (6.1), and Clinical Studies (14)]. The pharmacokinetics of rufinamide in the pediatric patients, ages 1 to less than 4 years of age is similar to children older than 4 years of age and adults [see Clinical Pharmacology (12.3)]. Safety and effectiveness in pediatric patients below the age of 1 year has not been established. 8.5 Geriatric Use Clinical studies of BANZEL did not include sufficient numbers 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. Pharmacokinetics of rufinamide in the elderly are similar to that in the young subjects [see Clinical Pharmacology (12.3)]. 8.6 Renal Impairment Rufinamide pharmacokinetics in patients with severe renal impairment (creatinine clearance < 30 mL/min) was similar to that of healthy subjects. Dose adjustment in patients undergoing dialysis should be considered [see Clinical Pharmacology (12.3)]. 8.7  Hepatic Impairment Use of BANZEL in patients with severe hepatic impairment (Child-Pugh score 10 to 15) is not recommended. Caution should be exercised in treating patients with mild (Child-Pugh score 5 to 6) to moderate (Child-Pugh score 7 to 9) hepatic impairment. 10 OVERDOSAGE Because strategies for the management of overdose are continually evolving, it is advisable to contact a Certified Poison Control Center to determine the latest recommendations for the management of an overdose of any drug. One overdose of 7200 mg per 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. 11 DESCRIPTION BANZEL (rufinamide) is a triazole derivative structurally unrelated to currently marketed antiepileptic drugs (AEDs). Rufinamide has the chemical name 1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4 carboxamide. It has an empirical formula of C10H8F2N4O and a molecular weight of 238.2. The drug substance is a white, crystalline, odorless, and slightly bitter tasting neutral powder. Rufinamide is practically insoluble in water, slightly soluble in tetrahydrofuran and in methanol, and very slightly soluble in ethanol and in acetonitrile. BANZEL is available for oral administration in film-coated tablets, scored on both sides, containing 200 and 400 mg of rufinamide. Inactive ingredients are colloidal silicon dioxide, corn starch crosscarmellose 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 is also available for oral administration as a liquid containing rufinamide at a concentration of 40 mg/mL. Inactive ingredients include microcrystalline cellulose and carboxymethylcellulose sodium, hydroxyethylcellulose, anhydrous citric acid, simethicone emulsion 30%, poloxamer 188, methylparaben, propylparaben, propylene glycol, potassium sorbate, noncrystallizing sorbitol solution 70%, and an orange flavor. 12  CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The precise mechanism(s) by which rufinamide exerts its antiepileptic effect is unknown. The results of in vitro studies suggest that the principal mechanism of action of rufinamide is modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the channel. Rufinamide (≥ 1 μM) significantly slowed sodium channel recovery from inactivation after a prolonged prepulse in cultured cortical neurons, and limited sustained repetitive firing of sodium-dependent action potentials (EC50 of 3.8 μM). 12.3 Pharmacokinetics Overview BANZEL oral suspension is bioequivalent on a mg per mg basis to BANZEL tablets. BANZEL is well absorbed after oral administration. However, the rate of absorption is relatively slow and the extent of absorption is decreased as dose is increased. The pharmacokinetics does not change with multiple dosing. Most elimination of rufinamide is via metabolism, with the primary metabolite resulting from enzymatic hydrolysis of the carboxamide moiety to form the carboxylic acid. This metabolic route is not cytochrome P450 dependent. There are no known active metabolites. Plasma half-life of rufinamide is approximately 6-10 hours. Absorption and Distribution 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. Based on urinary excretion, the extent of absorption was at least 85% following oral administration of a single dose of 600 mg rufinamide tablet under fed conditions. Multiple dose pharmacokinetics can be predicted from single dose data for both rufinamide and its metabolite. Given the dosing frequency of every 12 hours and the half-life of 6 to 10 hours, the observed steady-state peak concentration of about two to three times the peak concentration after a single dose is expected. 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 tablet, although the Tmax was not elevated [see Dosage and Administration (2.2)]. 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 per day. Metabolism Rufinamide is extensively metabolized but has no active metabolites. Following a radiolabeled dose of rufinamide, less than 2% of the dose was recovered unchanged in urine. The primary biotransformation pathway is carboxylesterase(s) mediated hydrolysis of the carboxamide group to the acid derivative CGP 47292. A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. There is no involvement of oxidizing cytochrome P450 enzymes or glutathione in the biotransformation process. 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. Rufinamide did not show any significant inhibition of P-glycoprotein in an invitro study. Elimination/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 Age Pediatrics Based on a population analysis which included a total of 115 patients, including 85 pediatric patients (24 patients ages 1 to 3 years, 40 patients ages 4 to 11 years, and 21 patients ages 12 to 17 years), the pharmacokinetics of rufinamide was similar across all age groups. Elderly The results of a study evaluating single-dose (400 mg) and multiple dose (800 mg per 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. Sex 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 and Caucasian subjects, after controlling for body size. Information on other races could not be obtained because of smaller numbers of these subjects. Renal Impairment Rufinamide pharmacokinetics in 9 patients with severe renal impairment (creatinine clearance < 30 mL per min) was similar to that of healthy subjects.  Patients undergoing dialysis 3 hours post rufinamide dosing showed a reduction in AUC and Cmax by 29% and 16%, respectively. Drug Interactions 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 a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. In pediatric patients, valproate administration may lead to elevated levels of rufinamide by up to 70% [see Drug Interactions (7.2)]. 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. Co-administration and pre-treatment of BANZEL (400 mg twice daily) and triazolam resulted in a 37% decrease in AUC and a 23% decrease in Cmax of triazolam, a CYP 3A4 substrate. Co-administration of BANZEL (800 mg twice daily for 14 days) and Ortho-Novum 1/35® resulted in a mean decrease in the ethinyl estradiol AUC0-24 of 22% and Cmax by 31% and norethindrone AUC0-24 by 14% and Cmax by 18%, respectively. The clinical significance of this decrease is unknown [see Drug Interactions (7.3)]. 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. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Rufinamide was given in the diet to mice at 40, 120, and 400 mg/kg per day and to rats at 20, 60, and 200 mg/kg per day for 2 years. The doses in mice were associated with plasma AUCs 0.1 to 1 times the human plasma AUC at the maximum recommended human dose (MRHD, 3200 mg/day). Increased incidences of tumors (benign bone tumors (osteomas) and/or hepatocellular adenomas and carcinomas) were observed in mice at all doses. Increased incidences of thyroid follicular adenomas were observed in rats at all but the low dose; the low dose is < 0.1 times the MRHD on a mg/m2 basis. Mutagenesis Rufinamide was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or the in vitro mammalian cell point mutation assay. Rufinamide was not clastogenic in the in vitro mammalian cell chromosomal aberration assay or the in vivo rat bone marrow micronucleus assay. Impairment of Fertility Oral administration of rufinamide (doses of 20, 60, 200, and 600 mg/kg per day) to male and female rats prior to mating and throughout mating, and continuing in females up to day 6 of gestation resulted in impairment of fertility (decreased conception rates and mating and fertility indices; decreased numbers of corpora lutea, implantations, and live embryos; increased preimplantation loss; decreased sperm count and motility) at all doses tested. Therefore, a no-effect dose was not established. The lowest dose tested was associated with a plasma AUC ≈ 0.2 times the human plasma AUC at the MRHD. 14  CLINICAL STUDIES Adult and Pediatric Patients ages 4 years and older The  effectiveness of BANZEL as adjunctive treatment for the seizures associated with Lennox-Gastaut Syndrome (LGS) in adult and pediatric patients ages 4 years and older was established in a single multicenter, double-blind, placebo-controlled, randomized, parallel-group study (N=138). Male and female patients (between 4 and 30 years of age) were included if they had a diagnosis of inadequately controlled seizures associated with LGS (including both atypical absence seizures and drop attacks) and were being treated with 1 to 3 concomitant stable dose AEDs. Each patient must have had at least 90 seizures in the month prior to study entry. After completing a 4-week Baseline Phase on stable therapy, patients were randomized to have BANZEL or placebo added to their ongoing therapy during the 12 -week Double-blind Phase. The Double-blind Phase consisted of 2 periods: the Titration Period (1 to 2 weeks) and the Maintenance Period (10 weeks). During the Titration Period, the dose was increased to a target dosage of approximately 45 mg/kg per day (3200 mg in adults of > 70 kg), given on a twice daily schedule. Dosage reductions were permitted during titration if problems in tolerability were encountered. Final doses at titration were to remain stable during the maintenance period. Target dosage was achieved in 88% of the BANZEL-treated patients. The majority of these patients reached the target dose within 7 days, with the remaining patients achieving the target dose within 14 days. The primary efficacy variables were: The percent change in total seizure frequency per 28 days; The percent change in tonic-atonic (drop attacks) seizure frequency per 28 days; Seizure severity from the Parent/Guardian Global Evaluation of the patient’s condition. This was a 7-point assessment performed at the end of the Double-blind Phase. A score of +3 indicated that the patient’s seizure severity was very much improved, a score of 0 that the seizure severity was unchanged, and a score of -3 that the seizure severity was very much worse. The results of the three primary endpoints are shown in Table 7 below. Table 7: Lennox -Gastaut Syndrome Trial Seizure Frequency Primary Efficacy Variable Results  Variable Placebo Rufinamide Median percent change in total seizure frequency per 28 days -11.7 -32.7 (p=0.0015) Median percent change in tonic-atonic seizure frequency per 28 days 1.4 -42.5 (p<0.0001) Improvement in Seizure Severity Rating from Global Evaluation 30.6 53.4 (p=0.0041) Pediatric Patients ages 1 to less than 4 years The effectiveness of BANZEL as adjunctive treatment for the seizures associated with Lennox-Gastaut Syndrome in pediatric patients ages 1 year to less than 4 years was established based on a single multi-center, open-label, active-controlled, randomized, pharmacokinetic bridging study. The pharmacokinetic profile of BANZEL is not significantly affected by age either as a continuous covariate (1 to 35 years) or as a categorical covariate (age categories: 1 to less than 4 years and 4 years of age and older), after body weight is taken into consideration.  16   HOW SUPPLIED/STORAGE AND HANDLING 16.1  How Supplied BANZEL 200 mg tablets (containing 200 mg rufinamide) are pink in color, film-coated, oblong-shape tablets, with a score on both sides, imprinted with “ 262” on one side. They are available in bottles of 120 (NDC 62856-582-52). BANZEL 400 mg tablets (containing 400 mg rufinamide) are pink in color, film-coated, oblong-shape tablets, with a score on both sides, imprinted with “ 263” on one side. They are available in bottles of 120 (NDC 62856-583-52). BANZEL oral suspension is an orange flavored liquid supplied in a polyethylene terephthalate (PET) bottle with child-resistant closure. The oral suspension is packaged with a dispenser set which contains a calibrated oral dosing syringe and an adapter. Store the oral suspension in an upright position. Use within 90 days of first opening the bottle, then discard any remainder. The oral suspension is available in bottles of 460 mL (NDC 62856-584-46). 16.2  Storage and Handling Store the tablets at 25ºC (77ºF); excursions permitted to 15º- 30ºC (59ºF - 86ºF). Protect from moisture. Replace cap securely after opening. Store the oral suspension at 25ºC (77ºF); excursions permitted to 15º- 30ºC (59ºF - 86ºF). Replace cap securely after opening. The cap fits properly in place when the adapter is in place. 17  PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Administration Information Advise patients to take BANZEL with food [see Dosage and Administration (2.2)]. Advise patients who are prescribed the oral suspension to shake the bottle vigorously before every administration and to use the adaptor and oral dosing syringe [see Dosage and Administration (2.2)]. Suicidal Thinking and Behavior Inform patients, their caregivers, and families that antiepileptic drugs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.1)]. Central Nervous System Reactions Inform patients about the potential for somnolence or dizziness and advise them 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 [see Warnings and Precautions (5.2)]. Multi-Organ Hypersensitivity Reactions Advise patients to notify their physician if they experience a rash associated with fever [see Warnings and Precautions (5.4)]. Drug Interactions Inform female patients of childbearing age that the concurrent use of BANZEL with hormonal contraceptives may render this method of contraception less effective. Recommend patients use additional non-hormonal forms of contraception when using BANZEL [see Drug Interactions (7.3)]. Inform patients that alcohol in combination with BANZEL may cause additive central nervous system effects. Pregnancy Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy. Encourage patients to enroll in the North American Antiepileptic Drug Pregnancy Registry if they become pregnant. To enroll, patients can call the toll free number 1-888-233-2334 [see Use in Specific Populations (8.1)]. Breast-feeding Advise patients to notify their physician if they are breast-feeding or intend to breast-feed [see Use in Specific Populations (8.3)]. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a3fa925-1abd-458a-bd57-4ae780a1ef2d 治疗癫痫药物Banzel口服获美国FDA及欧盟批准上市 【给药途径】口服（临床用片剂） 【开发厂商】诺华/卫材 【国外上市信息】2007年1月，欧盟上市。 【产品特点】卢非酰胺在结构上和已经上市的癫痫药物不相关，其主要通过限制神经元钠依赖性活动电位的点燃来发挥抗痉挛作用。卢非酰胺为广谱抗惊厥药物，治疗窗口宽，对之前治疗耐受的局部或返还性癫痫病人仍对卢非酰胺产生反应。该药与以往的抗癫痫药相比，不仅具有较好的抗癫痫作用，而且耐受性高，毒副反应小。 Rufinamide 痫治疗药物 [化学名]：1H-1,2,3-Triazole-4-carboxamide, 1-[(2,6-difluorophenyl)methyl]- [分子式]：C10H8F2N4O [CAS]：106308-44-5 [开发公司]：诺华公司/卫材公司获得日本授权 [开发阶段]：III 期临床（美国，适应症为癫痫）；Ⅱ期临床（美国，适应症为神经病理性疼痛） [ATC分类]：其他类抗癫痫药物（N03A-X） [给药途径]：口服 [简介]：Rufinamide [CGP 33101, RUF 331, Xilep TM] 是5-取代-苯烷基-3-氨基甲酰-4H-1,2,4-三唑类化合物的先导化合物，具有抗痉挛活性，目前由诺华公司作为抗癫痫药开发。在瑞士和美国已进入III 期临床开发阶段。在日本处于II期临床开发阶段。 Rufinamide对局部癫痫发作和泛发性强直-阵挛癫痫发作(tonic-clonic seizure)有治疗益处，可以联合给药，也可以单独给药。Rufinamide在结构上和已经上市的癫痫治疗药物不相关，其主要通过限制神经元钠依赖性活动电位的点燃来发挥抗痉挛作用。 Rufinamide的治疗窗口宽，对之前治疗耐受的局部或返发性癫痫病人仍对Rufinamide产生反应。除癫痫外，rufinamide还在进行治疗神经病理性疼痛的II期临床开发。卫材公司获得了该产品在日本的授权，该公司决定在2005年向美国和欧盟提出该产品的治疗癫痫的新药上市申请。 [药代动力学] 健康志愿者参加的临床试验表明rufinamide的片剂和混悬液剂型具有生物等效性。 片剂和混悬液的t1/2值分别为8.82和9.12小时。在服用400mg片剂或混悬液后的6.56或7.22小时，两种剂型的药物达到最大血药浓度，Cmax值分别3.03和3.32μg/ml。3名男性志愿者单次口服600mg 14C-标记的微晶型rufinamide，药物包装在明胶胶囊内，与食物同服。药物的吸收率>= 85%。放射活性和rufinamide的清除为一级指数反应(monoexponential)，平均t1/2为9小时。药物大部分（85%）通过肾脏清除。主要的代谢产物是无药理学活性的羧酸衍生物CGP 47292。一项应用471名病人数据进行的群体药代动力学研究发现rufinamide的给药剂量为1600mg/day时，药物的相对吸收程度要低于给药剂量为200-800mg/day的情况。性别或年龄对rufinamide的稳态药代动力学都没有影响。 儿童患者给药rufinamide 后的药代动力学和成人类似。 [不良反应] 50名对之前治疗耐受的局部发作或强直-阵挛发作病人接受rufinamide 400mg/day的治疗，之后逐渐增加到1600mg/day的剂量。Rufinamide的耐受性良好，最常出现的不良反应是疲乏（治疗组和对照组的发生率分别为20%和4%）和震颤（治疗组和对照组的发生率分别为12%和0）。9名儿童患者服用Rufinamide（最终剂量45mg/kg，以该剂量治疗2周），没有不良反应报告。 [药物相互作用]： 在一项体外研究中，rufinamide在≤300μmol/L的浓度下和不同底物以及人肝微粒体分级产物孵育以检验rufinamide对肝脏细胞色素P450的作用。细胞色素P450参与多种抗痉挛药物以及其它药物的代谢。Rufinamide对人肝脏细胞色素P450没有显著的抑制作用。一项开放标记，多剂量试验检测了rufinamide 和口服避孕药的相互作用。Rufinamide和Ortho-Novum 1/35同服可以显著降低炔诺酮和乙烯雌二醇的全身浓度，这种降低具有何种临床意义还不明了。 [临床试验]： 50名之前治疗耐受的局部发作或强直-阵挛发作病人接受rufinamide的辅助治疗，起始剂量为400mg/day，每周剂量增加400mg/day，直到最大剂量1600 mg/day。Rufinamide可以显著减少癫痫发作频率。Rufinamide组癫痫发作频率的中位值降低了42%，而安慰剂组发作频率的中位值则增加了52%。rufinamide 组中癫痫发作频率降低程度达到25%的患者比例（52%）显著高于安慰剂组(15%)。39% of rufinamide组中发作频率降低程度达到50%的患者比例为39%，高于安慰剂组16%的比例，但差距还没有达到统计学的显著性。9名儿童（4-16岁）难治性局部发作癫痫患者接受Rufinamide治疗，最高剂量为45mg/kg。4名患者（45%）的癫痫发作频率减少程度大于50%，1名患者减少程度小于50%，2名患者发作频率维持原状，2名患者发作频率有所增加。