BANZEL® (rufinamide)

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.

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).

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in children 4 years and older and adults.

USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. To enroll in the North American Antiepileptic Drug Pregnancy Registry call 1-888-233-2334, toll free.

Renal impairment: Renally impaired patients (creatinine clearance less than 30 mL/min) do not require any specific dosage change.  Adjusting the BANZEL dose for the loss of drug upon dialysis should be considered.

Hepatic impairment: Use in patients with severe hepatic impairment is not recommended. Caution should be exercised in treating patients with mild to moderate hepatic impairment.

• Suicidal behavior and ideation.
• Patients should be advised that BANZEL can cause Central Nervous System Reactions
• Caution should be used when administering BANZEL with other drugs that shorten the QT interval.
• Multi-organ Hypersensitivity Reactions have occurred in association with BANZEL. If this reaction is suspected, BANZEL should be discontinued and alternative treatment started.
• Withdrawal of AEDs. BANZEL should be withdrawn gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus.
• Status Epilepticus

DRUG INTERACTIONS
See Full Prescribing Information for effects of BANZEL on other AEDs, effects of other AEDs on BANZEL, and effects of BANZEL on other medication

• 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 on valproate should begin at a BANZEL dose lower than 10 mg/kg/day (children) or 400 mg/day (adults).
• Other AEDs can influence rufinamide concentrations. This effect is more pronounced in children than adults
• 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.

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.

The prescribed amount of the oral suspension should be measured using the provided adapter and dosing syringe

Children four years and older with LGS: 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.

Adults with LGS: 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 dose of 3200 mg/day, administered in two equally divided doses is reached.

DOSAGE AND ADMINISTRATION
BANZEL should be given with food. Tablets can be administered whole, as half tablets or crushed, for dosing flexibility.

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 BANZEL Oral Suspension Dosing Instructions for complete instructions on how to properly dose and administer the BANZEL 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 - package insert]

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 - package insert]

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 Population  - package insert].

Patients on Antiepileptic Drugs (AEDs)
Patients on valproate should begin at a BANZEL dose lower than 10 mg/kg/day (children) or 400 mg/day (adults). For effects of other AEDs on BANZEL see Drug Interactions.

Store the tablets at 25°C (77°F); excursions permitted to 15°C-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°C-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

© 2011 Eisai Inc. Printed in U.S.A