Drugs Details

Drugs Info of Banzel
Drugs Details
  • Drugs Type  : FDA
  • Date : 27th Dec 2014 02:19 am
  • Brand Name : Banzel
  • Generic Name : rufinamide (Pronunciation: roo FIN a mide)
Descriptions

BANZEL (rufinamide) is a triazole derivative structurally unrelated to currently marketed antiepileptic drugs (AEDs). Rufinamide has the chemical name 1-[(2,6-difluorophenyl)methyl]-1H­1,2,3-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® (rufinamide) Structural Formula Illustration

BANZEL (rufinamide tablets) 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 (rufinamide tablets) 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.

What are the possible side effects of rufinamide (Banzel)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, agitated, hostile, aggressive, restless, irritable, hyperactive, talkative, or have thoughts about suicide or hurting yourself.

Stop using rufinamide and call your doctor at once if you have any of these serious side effects:

  • fever, swollen...

Read All Potential Side Effects and See Pictures of Banzel »

What are the precautions when taking rufinamide tablets (Banzel)?

Before taking rufinamide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: family history of a certain heart problem (QT shortening in the EKG).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe kidney disease (including dialysis), liver disease, mental/mood disorders (such as depression, thoughts of suicide).

This drug may make you dizzy or drowsy or cause blurred/double vision....

Read All Potential Precautions of Banzel »

This monograph has been modified to include the generic and brand name in many instances.

Indications

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

Dosage Administration

BANZEL (rufinamide tablets) should be given with food. Tablets can be administered whole, as half tablets or crushed, for dosing flexibility.

BANZEL (rufinamide tablets) 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 BANZEL (rufinamide tablets) Oral Suspension Dosing Instructions for complete instructions on how to properly dose and administer the BANZEL (rufinamide tablets) Oral Suspension.

Patient with Lennox-Gastaut Syndrome

Children four years and older with Lennox-Gastaut syndrome: Treatment should be initiated at a daily dose of approximately 10 mg/kg/day administered in two equally divided doses. The dose should be increased by approximately 10 mg/kg increments every other day to a target dose of 45 mg/kg/day or 3200 mg/day, whichever is less, administered in two equally divided doses. It is not known whether doses lower than the target doses are effective.

Adults with Lennox-Gastaut syndrome: Treatment should be initiated at a daily dose of 400-800 mg/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/day, administered in two equally divided doses is reached. It is not known whether doses lower than 3200 mg are effective.

Patients with Renal Impairment

Renally impaired patients (creatinine clearance less than 30 mL/min) do not require any special dosage change when taking BANZEL [see CLINICAL PHARMACOLOGY ]

Patients Undergoing Hemodialysis

Hemodialysis may reduce exposure to a limited (about 30%) extent. Accordingly, adjusting the BANZEL (rufinamide tablets) dose during the dialysis process should be considered [see CLINICAL PHARMACOLOGY]

Patients with Hepatic Disease

Use of BANZEL (rufinamide tablets) 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 Population].

Patients on Antiepileptic Drugs (AEDs)

Patients on valproate should begin at a BANZEL (rufinamide tablets) dose lower than 10 mg/kg/day (children) or 400 mg/day (adults). For effects of other AEDs on BANZEL see DRUG INTERACTIONS.

How Supplied

Dosage Forms And Strengths

Film coated Tablets: 200 mg (pink) and 400 mg (pink). Tablets are scored on both sides.

Oral Suspension: 40mg/mL.

Storage And Handling

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 “ε 262” on one side. They are available in bottles of 30 (NDC 62856-582-30).

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 “ε 263” on one side. They are available in bottles of 120 (NDC 62856-583-52).

BANZEL (rufinamide tablets) 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).

Store the tablets at 25°C (77°F); excursions permitted to 15°- 30°C (59°F - 86°F). Protect from moisture. Replace cap securely after opening.

Store the oral suspension at 25°C (77°F); excursions permitted to 15°- 30°C (59°F - 86°F). Replace cap securely after opening. The cap fits properly in place when the adapter is in place.

Manufactured by: Eisai Co., Ltd. Marketed by Eisai Inc. Woodcliff Lake, NJ 07677. Revised March 2011

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Controlled Trials

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.

Placebo-controlled double-blind studies were performed in adults and in pediatric patients, down to age of 4, in other forms of epilepsy, in addition to the trial in Lennox-Gastaut syndrome. Data on CNS Reactions [see WARNINGS AND PRECAUTIONS] from the Lennox-Gastaut study are presented first. Because there is no reason to suspect that adverse reactions would substantially differ between these patient populations, safety data from all of these controlled studies are then presented. Most of these adverse reactions were mild to moderate and transient in nature.

Common central nervous system reactions in the controlled trial of patients 4 years or older with Lennox-Gastaut syndrome treated with BANZEL (rufinamide tablets) as adjunctive therapy [see WARNINGS AND PRECAUTIONS]

Somnolence was reported in 24.3% of BANZEL (rufinamide tablets) -treated patients compared to 12.5% of placebo patients and led to study discontinuation in 2.7% of treated patients compared to 0% of placebo patients. Fatigue was reported in 9.5% of BANZEL (rufinamide tablets) -treated patients compared to 7.8% of placebo patients. It led to study discontinuation in 1.4% of treated patients and 0% of placebo patients.

Dizziness was reported in 2.7% of BANZEL (rufinamide tablets) -treated patients compared to 0% of placebo patients, and did not lead to study discontinuation.

Ataxia and gait disturbance were reported in 5.4% and 1.4% of BANZEL (rufinamide tablets) -treated patients, respectively, and in no placebo patients. Balance disorder and abnormal coordination were each reported in 0% of BANZEL (rufinamide tablets) -treated patients and 1.6% of placebo patients. None of these reactions led to study discontinuation.

All Adverse Reactions for All Treated Patients with Epilepsy, Double-blind Adjunctive Therapy Studies: The most commonly observed ( ≥ 10%) adverse reactions in BANZEL (rufinamide tablets) -treated patients, when used as adjunctive therapy at all doses studied (200 to 3200 mg/day) with a higher frequency than in placebo were: headache, dizziness, fatigue, somnolence, and nausea.

Table 2 lists treatment-emergent adverse reactions that occurred in at least 3% of pediatric patients with epilepsy treated with BANZEL (rufinamide tablets) in controlled adjunctive studies and were numerically more common in patients treated with BANZEL (rufinamide tablets) than placebo.

At the target dose of 45 mg/kg/day for adjunctive therapy in children, the most commonly observed ( ≥ 3%) adverse reactions with an incidence greater than in placebo, for BANZEL (rufinamide tablets) were somnolence, vomiting and headache.

Table 2: Incidence (%) of Treatment-Emergent Adverse Reactions in all Pediatric Double-Blind Adjunctive Trials by Preferred Term at the Recommended Dose of 45 mg/kg/day (Adverse Reactions occurred in at least 3% of BANZEL (rufinamide tablets) -treated patients and occurred more frequently than in Placebo Patients)

Preferred Term BANZEL (rufinamide tablets)
(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
Abdominal Pain Upper 3 2
Aggression 3 2
Ear Infection 3 1
Disturbance in Attention 3 1
Pruritis 3 0

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

At all doses studied of up to 3200 mg/day given as adjunctive therapy in adults, the most commonly observed ( ≥ 3%) adverse reactions, and with the greatest increase in incidence compared to placebo, for BANZEL (rufinamide tablets) were dizziness, fatigue, nausea, diplopia, vision blurred, and ataxia.

Table 3: Incidence (%) of Treatment-Emergent Adverse Reactions in all Adult Double-Blind Adjunctive Trials (up to 3200mg/day) by Preferred Term (Adverse Reactions occurred in at least 3% of BANZEL (rufinamide tablets) -treated patients and occurred more frequently than in Placebo Patients)

Preferred Term BANZEL (rufinamide tablets)
(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
Vision Blurred 6 2
Vomiting 5 4
Ataxia 4 0
Abdominal Pain Upper 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, 9.0% of patients receiving BANZEL (rufinamide tablets) as adjunctive therapy and 4.4% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (rufinamide tablets) ( > 1%) used as adjunctive therapy were generally similar in adults and children.

In pediatric double-blind adjunctive clinical studies, 8.0% of patients receiving BANZEL (rufinamide tablets) 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 (rufinamide tablets) ( > 1%) used as adjunctive therapy are presented in Table 4.

Table 4: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials (At The Recommended Dose of 45mg/kg/day) in Pediatric Patients

Preferred Term BANZEL (rufinamide tablets)
(N=187)
%
Placebo
(N=182)
%
Convulsion 2 1
Rash 2 1
Fatigue 2 0
Vomiting 1 0

In adult double-blind adjunctive clinical studies (up to 3200 mg/day), 9.5% of patients receiving BANZEL (rufinamide tablets) 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 (rufinamide tablets) ( > 1%) used as adjunctive therapy are presented in Table 5.

Table 5: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials (up to 3200 mg/day) in Adult Patients

Preferred Term BANZEL (rufinamide tablets)
(N=823)
%
Placebo
(N=376)
%
Dizziness 3 1
Fatigue 2 1
Headache 2 1
Nausea 1 0
Ataxia 1 0
Other Adverse Events Observed During Clinical Trials

BANZEL (rufinamide tablets) has been administered to 1978 individuals during all epilepsy clinical trials (placebo­controlled and open-label). Adverse events 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 events, 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 (rufinamide tablets) 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.

Read the Banzel (rufinamide tablets) Side Effects Center for a complete guide to possible side effects

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 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.

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.

Effects of BANZEL (rufinamide tablets) 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 (rufinamide tablets) with other AEDs.

Table 6: Summary of drug-drug interactions of BANZEL (rufinamide tablets) 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 (rufinamide tablets) concentrations at the maximum recommended dose of BANZEL (rufinamide tablets) .
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 (rufinamide tablets) clearance.
e) All compounds of the benzodiazepine class were pooled to examine for 'class effect' on BANZEL (rufinamide tablets) 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.

Effects of Other AEDs on BANZEL (rufinamide tablets)

Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital appear to increase the clearance of BANZEL (rufinamide tablets) (see Table 6). Given that the majority of clearance of BANZEL (rufinamide tablets) 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: Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. In children, valproate administration may lead to elevated levels of rufinamide by up to 70%. Patients stabilized on BANZEL (rufinamide tablets) 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 (rufinamide tablets) dose lower than 10 mg/kg/day (children) or 400 mg/day (adults) [see DOSAGE AND ADMINISTRATION].

Effects of BANZEL (rufinamide tablets) on other Medications

Hormonal contraceptives: Co-administration of BANZEL (rufinamide tablets) (800 mg BID 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. Female patients of childbearing age should be warned that the concurrent use of BANZEL (rufinamide tablets) with hormonal contraceptives may render this method of contraception less effective. Additional non-hormonal forms of contraception are recommended when using BANZEL [see PATIENT INFORMATION].

Triazolam: Co-administration and pre-treatment with BANZEL (rufinamide tablets) (400 mg bid) 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 (rufinamide tablets) (400mg bid) resulted in no change in AUC and Cmax of olanzapine, a CYP 1A2 substrate.

Drug Abuse And Dependence

The abuse and dependence potential of BANZEL (rufinamide tablets) has not been evaluated in human studies.

Read the Banzel Drug Interactions Center for a complete guide to possible interactions

Learn More »

This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including Banzel (rufinamide tablets) , 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 one 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 Per1000 Patients Drug Patients with Events Per1000 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 (rufinamide tablets) 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, the prescriber needs to 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.

Central Nervous System Reactions

Use of BANZEL (rufinamide tablets) has been associated with central nervous system-related adverse reactions. 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 [see ADVERSE REACTIONS].

QT Shortening

Formal cardiac ECG studies demonstrated shortening of the QT interval (mean = 20 msec, for doses > 2400 mg twice daily) with BANZEL (rufinamide tablets) treatment. In a placebo-controlled study of the QT interval, a higher percentage of BANZEL (rufinamide tablets) -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/day. Moreover, there was no signal for drug-induced sudden death or ventricular arrhythmias.

The degree of QT shortening induced by BANZEL (rufinamide tablets) 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 (rufinamide tablets) . Caution should be used when administering BANZEL (rufinamide tablets) with other drugs that shorten the QT interval [see CONTRAINDICATIONS].

Multi-organ Hypersensitivity Reactions

Multi-organ hypersensitivity syndrome, a serious condition sometimes induced by antiepileptic drugs, has occurred in association with BANZEL (rufinamide tablets) therapy in clinical trials. One patient experienced rash, urticaria, facial edema, fever, elevated eosinophils, stuperous state, and severe hepatitis, beginning on day 29 of BANZEL (rufinamide tablets) therapy and extending over a course of 30 days of continued BANZEL (rufinamide tablets) therapy with resolution 11 days after discontinuation. Additional possible cases presented with rash and one or more of the following: fever, elevated liver function studies, hematuria, and lymphadenopathy. These cases occurred in children less than 12 years of age, within four weeks of treatment initiation, and were noted to resolve and/or improve upon BANZEL (rufinamide tablets) 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. Because this disorder is variable in its expression, other organ system signs and symptoms not noted here may occur. If this reaction is suspected, BANZEL (rufinamide tablets) should be discontinued and alternative treatment started.

All patients who develop a rash while taking BANZEL (rufinamide tablets) must be closely supervised.

Withdrawal of AEDs

As with all antiepileptic drugs, BANZEL (rufinamide tablets) 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 (rufinamide tablets) discontinuation was achieved by reducing the dose by approximately 25% every two days.

Status Epilepticus

Estimates of the incidence of treatment emergent status epilepticus among patients treated with BANZEL (rufinamide tablets) are difficult because standard definitions were not employed. In a controlled Lennox-Gastaut syndrome trial, 3 of 74 (4.1 %) BANZEL (rufinamide tablets) -treated patients had episodes that could be described as status epilepticus in the BANZEL (rufinamide tablets) -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 (rufinamide tablets) -treated patients had episodes that could be described as status epilepticus compared with none of 635 patients in the placebo-treated patients.

Laboratory Tests

Leucopenia (white cell count < 3X109 L) was more commonly observed in BANZEL (rufinamide tablets) -treated patients (43 of 1171, 3.7%) than placebo-treated patients (7 of 579, 1.2%) in all controlled trials.

Patient Counseling Information

Patients should be informed of the availability of a Medication guide and they should be instructed to read the Medication Guide prior to taking BANZEL (rufinamide tablets) .

Patients should be instructed to take BANZEL (rufinamide tablets) only as prescribed.

Suicidal Thinking and Behavior

Patients, their caregivers, and families should be informed 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.

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

Patients should be advised to notify their physician if they experience a rash associated with fever.

BANZEL (rufinamide tablets) should be taken with food.

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 (rufinamide tablets) to gauge whether it adversely affects their mental and/or motor performance.

Female patients of childbearing age should be warned that the concurrent use of BANZEL (rufinamide tablets) 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 (rufinamide tablets) .

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. They should also be encouraged 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].

Patients should be advised to notify their physician if they are breast-feeding or intend to breast-feed.

Patients who are prescribed the oral suspension should be advised to shake the bottle vigorously before every administration and to use the adaptor and oral dosing syringe.

When applicable patients should be advised that Banzel (rufinamide tablets) oral suspension does not contain lactose or gluten and is dye-free. The oral suspension does contain carbohydrates.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Rufinamide was given in the diet to mice at 40, 120, and 400 mg/kg/day and to rats at 20, 60, and 200 mg/kg/day for two 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/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.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. BANZEL (rufinamide tablets) 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/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/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/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/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 (rufinamide tablets) physicians are advised to recommend that pregnant patients taking BANZEL (rufinamide tablets) 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/.

Labor and Delivery

The effect of BANZEL (rufinamide tablets) on labor and delivery in humans is not known.

Nursing Mothers

Rufinamide is likely to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from BANZEL (rufinamide tablets) , a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness in patients with Lennox-Gastaut syndrome have not been established in children less than 4 years. The pharmacokinetics of rufinamide in the pediatric population (age 4-17 years) is similar to that in the adults [see CLINICAL PHARMACOLOGY]

Geriatric Use

Clinical studies of BANZEL (rufinamide tablets) 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]

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 DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Hepatic Impairment

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

This monograph has been modified to include the generic and brand name in many instances.

OverDose

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/day BANZEL (rufinamide tablets) 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 (rufinamide tablets) . 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.

ContrainDications

BANZEL (rufinamide tablets) is contraindicated in patients with Familial Short QT syndrome [see WARNINGS AND PRECAUTIONS, QT Shortening ]

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

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).

Pharmacokinetics

Overview

BANZEL (rufinamide tablets) oral suspension is bioequivalent on a mg per mg basis to BANZEL (rufinamide tablets) tablets. BANZEL (rufinamide tablets) 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 (rufinamide tablets) , peak plasma concentrations occur between 4 and 6 hours (Tmax) both under fed and fasted conditions. BANZEL (rufinamide tablets) 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. Clinical trials were performed under fed conditions and dosing is recommended with food [see DOSAGE AND ADMINISTRATION].

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.

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 in-vitro 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

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 and Caucasian subjects, after controlling for body size. Information on other races could not be obtained because of smaller numbers of these subjects.

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.

Elderly: 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. Renal Impairment: Rufinamide pharmacokinetics in 9 patients with severe renal impairment (creatinine clearance < 30 mL/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. Adjusting rufinamide dose for the loss of drug upon dialysis should be considered.

Hepatic Impairment: There have been no specific studies investigating the effect of hepatic impairment on the pharmacokinetics of rufinamide. Therefore, use in patients with severe hepatic impairment is not recommended. Caution should be exercised in treating patients with mild to moderate hepatic impairment.

Clinical Studies

The effectiveness of BANZEL (rufinamide tablets) as adjunctive treatment for the seizures associated with Lennox-Gastaut syndrome (LGS) 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 (rufinamide tablets) 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/day (3200 mg in adults of > 70kg), given on a b.i.d. 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 (rufinamide tablets) -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)

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Medication Guide

BANZEL
(ban-'zel)
[rufinamide] Tablets and Oral Suspension

Read this Medication Guide before you start taking BANZEL (rufinamide tablets) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about BANZEL (rufinamide tablets) ?

Do not stop taking BANZEL (rufinamide tablets) without first talking to your healthcare provider.

Stopping BANZEL (rufinamide tablets) suddenly can cause serious problems.

BANZEL (rufinamide tablets) can cause serious side effects, including:

1. Like other antiepileptic drugs, BANZEL (rufinamide tablets) may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

  • thoughts about suicide or dying
  • attempt to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry, or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood
  • Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

  • Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
  • Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop BANZEL (rufinamide tablets) without first talking to a healthcare provider.

  • Stopping BANZEL (rufinamide tablets) suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).

2. BANZEL (rufinamide tablets) may cause you to feel sleepy, tired, weak, dizzy or have problems with coordination and walking.

What is BANZEL (rufinamide tablets) ?

BANZEL (rufinamide tablets) is a prescription medicine used with other medicines to treat seizures associated with Lennox-Gastaut syndrome (LGS) in adults and children 4 years of age and older.

It is not known if BANZEL (rufinamide tablets) is safe and effective in the treatment of Lennox-Gastaut syndrome in children under 4 years of age.

Who should not take BANZEL (rufinamide tablets) ?

Do not take BANZEL (rufinamide tablets) if you have a genetic condition called familial short QT syndrome, a problem that affects the electrical system of the heart.

What should I tell my healthcare provider before taking BANZEL (rufinamide tablets) ?

Before you take BANZEL (rufinamide tablets) , tell your healthcare provider if you:

  • have heart problems
  • have liver problems
  • have any other medical problems
  • have or have had suicidal thoughts or actions, depression or mood problems
  • are pregnant or plan to become pregnant. It is not known if BANZEL (rufinamide tablets) can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking BANZEL (rufinamide tablets) . You and your healthcare provider will decide if you should take BANZEL (rufinamide tablets) while you are pregnant.
  • BANZEL (rufinamide tablets) may make certain types of birth control less effective. Talk to your healthcare provider about the best birth control methods for you while you take BANZEL (rufinamide tablets) .
    • If you become pregnant while taking BANZEL (rufinamide tablets) , talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic medicines during pregnancy.
  • are breastfeeding or plan to breastfeed. BANZEL (rufinamide tablets) may pass into your breast milk. You and your healthcare provider should decide if you will take BANZEL (rufinamide tablets) or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non­prescription medicines, vitamins, and herbal supplements. Taking BANZEL (rufinamide tablets) with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist each time you get a new medicine.

How should I take BANZEL (rufinamide tablets) ?

  • Take BANZEL (rufinamide tablets) exactly as your healthcare provider tells you. Your healthcare provider will tell you how much BANZEL (rufinamide tablets) to take.
  • Your healthcare provider may change your dose. Do not change your dose of BANZEL (rufinamide tablets) without talking to your healthcare provider.
  • Take BANZEL (rufinamide tablets) with food.
  • BANZEL (rufinamide tablets) tablets can be swallowed whole, cut in half or crushed.
  • If you take BANZEL (rufinamide tablets) Oral Suspension instead of BANZEL (rufinamide tablets) tablets, shake the bottle well before you take each dose. Measure your dose of BANZEL (rufinamide tablets) Oral Suspension using the bottle adapter and dosing syringes provided.
    See the complete Instructions for Use below for information on how to use the dosing syringes and measure your dose of BANZEL (rufinamide tablets) Oral Suspension.
  • If you take too much BANZEL (rufinamide tablets) , call your local Poison Control Center or get emergency medical help right away.

What should I avoid while taking BANZEL (rufinamide tablets) ?

  • Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking BANZEL (rufinamide tablets) until you talk to your healthcare provider. BANZEL (rufinamide tablets) taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how BANZEL (rufinamide tablets) affects you. BANZEL (rufinamide tablets) can slow your thinking and motor skills.

What are the possible side effects of BANZEL (rufinamide tablets) ?

See “What is the most important information I should know about BANZEL (rufinamide tablets) ?”

BANZEL (rufinamide tablets) may cause serious side effects including:

  • BANZEL (rufinamide tablets) can also cause allergic reactions or serious problems which may affect organs and other parts of your body like the liver or blood cells. You may or may not have a rash with these types of reactions.

Call your healthcare provider right away if you have any of the following. Symptoms may include:

    • swelling of your face, eyes, lips, or tongue
    • trouble swallowing or breathing
    • a skin rash
    • hives
    • fever, swollen glands, or sore throat that do not go away or come and go
    • swollen glands
    • yellowing of your skin or eyes
    • dark urine
    • unusual bruising or bleeding
    • severe fatigue or weakness
    • severe muscle pain
  • Your seizures happen more often or become worse

Call your healthcare provider right away if you have any of the symptoms listed above.

The most common side effects of BANZEL (rufinamide tablets) include:

  • headache
  • dizziness
  • tiredness
  • sleepiness
  • nausea
  • vomiting

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects of BANZEL (rufinamide tablets) . For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800­FDA-1088.

How should I store BANZEL (rufinamide tablets) ?

  • Store BANZEL (rufinamide tablets) tablets and oral suspension at 59°F to 86°F (15°C to 30°C).

Tablets

  • Keep BANZEL (rufinamide tablets) tablets in a dry place.

Oral Suspension

  • Replace the cap securely after opening.
  • Keep BANZEL (rufinamide tablets) Oral Suspension in an upright position.
  • Use BANZEL (rufinamide tablets) Oral Suspension within 90 days of first opening the bottle.

Keep BANZEL (rufinamide tablets) and all medicines out of the reach of children.

General Information about the safe and effective use of BANZEL (rufinamide tablets)

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use BANZEL (rufinamide tablets) for a condition for which it was not prescribed. Do not give BANZEL (rufinamide tablets) to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about BANZEL (rufinamide tablets) . If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about BANZEL (rufinamide tablets) that is written for health professionals.

For more information, go to www.banzel (rufinamide tablets) .com or call 1-888-274-2378.

What are the ingredients in BANZEL (rufinamide tablets) ?

Tablets

Active ingredient: rufinamide

Inactive ingredients: 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.

Oral Suspension

Active ingredient: rufinamide

Inactive ingredients: microcrystalline cellulose and carboxymethylcellulose sodium, hydroxyethylcellulose, anhydrous citric acid, simethicone emulsion 30%, poloxamer 188, methylparaben, propylparaben, propylene glycol, potassium sorbate, noncrystallizing sorbitol solution 70%, orange flavor.

The oral suspension does not contain lactose or gluten and is dye-free. The oral suspension does contain carbohydrates.

Instructions for Use BANZEL

(ban-'zel)
[rufinamide] Oral Suspension

Read the Instructions for Use before using BANZEL (rufinamide tablets) Oral Suspension and each time you get a refill. There may be new information. This leaflet does not take the place of talking with the doctor about your medical condition or treatment.

Prepare the BANZEL (rufinamide tablets) Oral Suspension dose

You will need the following supplies: See Figure A

  • BANZEL (rufinamide tablets) Oral Suspension bottle
  • Bottle adapter
  • Dosing syringe (2 dosing syringes are included in the BANZEL (rufinamide tablets) Oral Suspension box)

Figure A

BANZEL Oral Suspension dose supplies - Illustration

Your total daily dose of BANZEL (rufinamide tablets) Oral Suspension is______mL.

Take BANZEL (rufinamide tablets) in 2 equally divided doses:

Morning dose = _____mL Evening dose =______mL

Note: The doctor may change your dose, especially when you are first starting BANZEL (rufinamide tablets) Oral Suspension.

If your morning and evening doses are more than 20 mL each, measure each dose using either:

  • 2 syringes, or
  • 1 syringe, taking two steps to draw up the medicine in that same syringe

Step 1. Remove the BANZEL (rufinamide tablets) Oral Suspension bottle, bottle adapter, and 2 syringes from the box. See Figure A

Step 2. Shake the bottle well before each use. See Figure B

Figure B

Shake the bottle well before each use - Illustration

Step 3. Uncap the bottle and insert the bottle adapter into the bottle. See Figure C.

Figure C

Uncap the bottle and insert the bottle adapter into the bottle - Illustration

Once the bottle adapter is installed, it cannot be removed. See Figure D

Figure D

Once the bottle adapter is installed, it cannot be removed - Illustration

Step 4. Check the morning or evening dose in milliliters (mL) as prescribed by your doctor. Locate this number on the syringe. See Figure E

Figure E

Check dosage on the syringe - Illustration

Step 5. Insert the syringe into the upright bottle and push the plunger all the way down. See Figure F

Figure F

Insert the syringe into the upright bottle - Illustration

Step 6. With the syringe in place, turn the bottle upside down. Pull the plunger to the number of mL needed (the amount of liquid medicine in Step 4). See Figure G.

Figure G

Pull the plunger to the desired dose - Illustration

Measure the mLs of medicine from the white layer at the end of the plunger, not the black layer. See Figure H

Figure H

Measure the desired dose of medicine from the white layer - Illustration

Step 7. If the dose is more than 20 mL, you can either use:

  • 2 syringes, or
  • 1 syringe, taking two steps to draw up the medicine in that same syringe

For example:

If your dose is 30 mL, draw up 20 mL in the first syringe and the remaining 10 mL in the second syringe.

or

If your dose is 30 mL, draw up 20 mL in the single syringe and squirt the medicine into your mouth, then draw up the remaining 10 mL in that same syringe.

Repeat Steps 4 through 6 when drawing up the remaining dose of medicine, if your dose is more than 20 mL.

Step 8. Remove the syringe from the bottle adapter.

Step 9. Slowly squirt BANZEL (rufinamide tablets) directly into the corner of your mouth. If you need 2 syringes for your dose, slowly squirt the medicine from the first syringe into your mouth, then slowly squirt the medicine from the second syringe into your mouth. See Figure I

Figure I

Slowly squirt the medicine from the second syringe into your mouth - Illustration

Step 10. Rinse the syringe (or syringes) with tap water after each use. See Figure J

  • Fill a cup with water
  • Pull back on the plunger and draw the water from the cup into the syringe
  • Push on the plunger to release the water into the sink

Figure J

Rinse the syringe - Illustration

Step 11. Cap the bottle tightly. The cap will fit over the bottle adapter. Store the bottle upright at 59°F to 86°F (15°C to 30°C). See Figure K

Figure K

Cap the bottle tightly - Illustration

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

RUFINAMIDE - ORAL

 

(roo-FIN-a-mide)

 

COMMON BRAND NAME(S): Banzel

 

USES: Rufinamide is used with other medications to prevent or control seizures (epilepsy) associated with Lennox-Gastaut syndrome (LGS) in people aged 4 and older.

This medication is an anticonvulsant. Rufinamide is thought to work by acting on the sodium channels in the brain that carry excessive electrical charges that may cause seizures.

 

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using rufinamide and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth with food, usually twice daily or as directed by your doctor.

If you are using the suspension form of this medication, shake the bottle well before each dose. Measure each dose carefully with the provided oral dosing syringe. Do not use a household spoon because you may not get the correct dose. Rinse the syringe with tap water after each use.

To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. It is very important to follow your doctor's dosing instructions exactly. It may take several weeks to reach the best dose for you and to get the full benefit from this medication. Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. This drug works best when the amount of medicine in your body is kept at a constant level. Therefore, it is best to take rufinamide at evenly spaced intervals throughout the day and night.

Do not stop taking this medication without consulting your doctor. Some conditions (such as seizures) may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Tell your doctor if your condition does not improve or worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Drowsiness, dizziness, loss of coordination, trouble walking, tiredness, headache, nausea, vomiting, loss of appetite, or blurred/double vision may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor immediately if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

Tell your doctor immediately if any of these rare but very serious side effects occur: stomach/abdominal pain, yellowing eyes/skin, dark urine, bloody urine, swollen glands.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, fever, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Banzel (rufinamide tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking rufinamide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: family history of a certain heart problem (QT shortening in the EKG).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe kidney disease (including dialysis), liver disease, mental/mood disorders (such as depression, thoughts of suicide).

This drug may make you dizzy or drowsy or cause blurred/double vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication may pass into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: valproate.

This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use additional reliable birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as diazepam, triazolam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as liver function tests, complete blood counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. If using the suspension, store the bottle upright. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Banzel

Generic Name: rufinamide (Pronunciation: roo FIN a mide)

  • What is rufinamide (Banzel)?
  • What are the possible side effects of rufinamide (Banzel)?
  • What is the most important information I should know about rufinamide (Banzel)?
  • What should I discuss with my healthcare provider before taking rufinamide (Banzel)?
  • How should I take rufinamide (Banzel)?
  • What happens if I miss a dose (Banzel)?
  • What happens if I overdose (Banzel)?
  • What should I avoid while taking rufinamide (Banzel)?
  • What other drugs will affect rufinamide (Banzel)?
  • Where can I get more information?

What is rufinamide (Banzel)?

Rufinamide is an anti-epileptic medication, also called an anticonvulsant.

Rufinamide is used in combination with other medications to treat seizures caused by Lennox-Gastaut syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

Rufinamide may also be used for purposes not listed in this medication guide.

What are the possible side effects of rufinamide (Banzel)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, agitated, hostile, aggressive, restless, irritable, hyperactive, talkative, or have thoughts about suicide or hurting yourself.

Stop using rufinamide and call your doctor at once if you have any of these serious side effects:

  • fever, swollen glands, body aches, flu symptoms, feeling very weak or tired;
  • painful sores in or around your eyes or mouth, sore throat, trouble swallowing;
  • loss of balance or coordination, trouble walking;
  • skin rash, easy bruising or bleeding, severe tingling, numbness, pain, severe muscle pain or weakness;
  • upper stomach pain, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes);
  • chest pain, irregular heart rhythm, feeling short of breath;
  • confusion, nausea and vomiting, swelling, rapid weight gain;
  • lower back pain, bloody urine, urinating less than usual;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • new or worsening cough with fever, trouble breathing; or
  • worsening of seizures.

Less serious side effects may include:

  • headache;
  • dizziness, drowsiness;
  • increased or decreased appetite;
  • nausea, vomiting;
  • stuffy nose, sinus pain; or
  • blurred vision.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Banzel (rufinamide tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about rufinamide (Banzel)?

You should not use this medication if you are allergic to rufinamide, or if you have a genetic heart rhythm disorder called "Short QT syndrome."

Before taking rufinamide, tell your doctor if you have heart disease, liver disease, kidney disease (or if you are on dialysis), or a history of depression, mental illness, or suicidal thoughts or actions.

It is not known whether rufinamide will harm an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking rufinamide for seizures. Do not start or stop taking rufinamide during pregnancy without your doctor's advice.

You may have thoughts about suicide while taking this medication. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, agitated, hostile, aggressive, restless, irritable, hyperactive, talkative, or have thoughts about suicide or hurting yourself.

Do not stop using rufinamide without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using rufinamide suddenly. You may need to use less and less before you stop the medication completely.

Contact your doctor if your seizures get worse or you have them more often while taking rufinamide.

Side Effects Centers
  • Banzel

Patient Detailed How Take

What should I discuss with my healthcare provider before taking rufinamide (Banzel)?

You should not use this medication if you are allergic to rufinamide, or if you have a genetic heart rhythm disorder called "Short QT syndrome."

To make sure you can safely take rufinamide, tell your doctor if you have any of these other conditions:

  • heart disease;
  • liver disease;
  • kidney disease (or if you are on dialysis); or
  • a history of depression, mental illness, or suicidal thoughts or actions.

You may have thoughts about suicide while taking this medication. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

FDA pregnancy category C. It is not known whether rufinamide will harm an unborn baby, but having a seizure during pregnancy could harm both mother and baby. Do not start taking rufinamide without telling your doctor if you are pregnant or planning to become pregnant. If you become pregnant while taking rufinamide, do not stop taking the medicine without your doctor's advice.

Seizure control is very important during pregnancy. The benefit of preventing seizures may outweigh any risks posed by taking rufinamide. Follow your doctor's instructions about taking rufinamide while you are pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of rufinamide on the baby.

Rufinamide can make birth control pills less effective. Ask your doctor about using a non hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking rufinamide.

Rufinamide can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using rufinamide.

Rufinamide should not be given to a child younger than 4 years old.

How should I take rufinamide (Banzel)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take rufinamide with food.

The rufinamide tablet may be swallowed whole, crushed, or cut in half.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. Do not use a regular table spoon to measure the liquid. If you do not have a dosing syringe or dose-measuring device, ask your pharmacist for one.

Do not stop using rufinamide without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using rufinamide suddenly. You may need to use less and less before you stop the medication completely.

Wear a medical alert tag or carry an ID card stating that you take rufinamide. Any medical care provider who treats you should know that you take seizure medication.

Use rufinamide regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. Contact your doctor if your seizures get worse or you have them more often while taking rufinamide.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Store the liquid medicine in an upright position. Throw away any unused liquid after 90 days.

Side Effects Centers
  • Banzel

Patient Detailed Avoid Taking

What happens if I miss a dose (Banzel)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Banzel)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking rufinamide (Banzel)?

Drinking alcohol can increase certain side effects of rufinamide.

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

What other drugs will affect rufinamide (Banzel)?

Before using rufinamide, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for depression or anxiety). They can add to sleepiness caused by rufinamide.

Tell your doctor about all other seizure medications you use, especially:

  • carbamazepine (Carbatrol, Equetro, Tegretol);
  • phenobarbital (Luminal, Solfoton);
  • phenytoin (Dilantin);
  • primidone (Mysoline); or
  • valproic acid (Depakene, Stavzor).

This list is not complete and other drugs may interact with rufinamide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about rufinamide.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 2.01. Revision date: 10/16/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers
  • Banzel

Rx Scoops
Featured Topics
Advertisements
Copyrights ©2014: Rx Scoops - Designed & Developed By - GOIGI