Introduction
Banzel (rufinamide) is an antiepileptic drug (AED) approved by the U.S. Food and Drug Administration (FDA) for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 1 year of age and older. Developed by Eisai Inc., this triazole derivative represents an important therapeutic option for managing treatment-resistant epilepsy syndromes.
Mechanism of Action
Rufinamide exerts its antiepileptic effects primarily through modulation of sodium channel activity. The drug prolongs the inactive state of voltage-gated sodium channels, thereby limiting sustained repetitive neuronal firing. This mechanism stabilizes neuronal membranes and reduces synaptic transmission of epileptiform activity. Unlike some other sodium channel blockers, rufinamide appears to have preferential activity against sodium channels that fire at high frequencies, which may explain its particular efficacy in seizure types characteristic of Lennox-Gastaut syndrome.
Indications
- FDA-approved: Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 1 year of age and older
- Off-label uses: Some evidence supports use in other refractory epilepsy syndromes including:
- Other generalized epilepsy syndromes - Focal-onset seizures - Epileptic spasms
Dosage and Administration
Initial dosing:- Adults and adolescents (≥17 years): 400-800 mg/day in two divided doses
- Children (1-17 years): 10 mg/kg/day in two divided doses
- Adults: 1600-3200 mg/day in two divided doses
- Children: 45 mg/kg/day (maximum 3200 mg/day) in two divided doses
- Renal impairment: Use with caution in severe impairment
- Hepatic impairment: Contraindicated in severe hepatic impairment
- Elderly: Consider lower starting doses
- Pediatric: Approved for use down to 1 year of age
Pharmacokinetics
Absorption: Oral bioavailability is approximately 85% when taken with food. Tmax occurs 4-6 hours after administration. Distribution: Volume of distribution is approximately 50-80 L. Protein binding is approximately 34%, primarily to albumin. Metabolism: Extensive hepatic metabolism primarily via carboxyl esterase-mediated enzymatic hydrolysis, with no significant cytochrome P450 involvement. Elimination: Primarily renal excretion (85%) of metabolites, with less than 2% excreted unchanged. Half-life is approximately 6-10 hours.Contraindications
- Hypersensitivity to rufinamide or any component of the formulation
- Familial short QT syndrome
- Severe hepatic impairment
Warnings and Precautions
QT shortening: Rufinamide causes dose-dependent shortening of the QT interval. Avoid use in patients with familial short QT syndrome and consider risks in patients with known cardiac conduction abnormalities. Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal thoughts or behavior. Central nervous system effects: May cause somnolence, fatigue, coordination abnormalities, cognitive dysfunction, and psychiatric symptoms. Multi-organ hypersensitivity reactions: Discontinue immediately if rash appears with systemic symptoms. Withdrawal seizures: Abrupt discontinuation may increase seizure frequency; taper gradually. Pregnancy considerations: Available data suggest increased risk of major congenital malformations; use only if potential benefit justifies potential risk.Drug Interactions
Strong CYP enzyme inducers:- Carbamazepine, phenytoin, phenobarbital, primidone: May decrease rufinamide concentrations by approximately 25-46%
Adverse Effects
Common (≥10%):- Headache (27%)
- Dizziness (19%)
- Fatigue (16%)
- Somnolence (13%)
- Nausea (11%)
- QT interval shortening
- Multi-organ hypersensitivity reactions
- Suicidal ideation and behavior
- Status epilepticus
- Leukopenia (2%)
- Seizure exacerbation
Monitoring Parameters
- Seizure frequency and type: Document baseline and monitor response
- ECG: Baseline and periodic monitoring for QT interval changes
- Complete blood count: Monitor for leukopenia
- Liver function tests: Baseline and periodic monitoring
- Renal function: In patients with renal impairment
- Psychiatric symptoms: Monitor for depression, suicidal thoughts
- Therapeutic drug monitoring: Not routinely required but may be useful
Patient Education
- Take medication exactly as prescribed with food
- Do not stop abruptly due to risk of increased seizures
- Report any skin rash immediately, especially if accompanied by fever
- May cause drowsiness or dizziness; avoid driving or operating machinery until effects are known
- Use effective non-hormonal contraception if taking oral contraceptives
- Report mood changes, depression, or suicidal thoughts
- Keep all medical appointments for monitoring
- Inform all healthcare providers about Banzel use before starting new medications
References
1. FDA Prescribing Information: Banzel (rufinamide). Revised 2022. 2. Wheless JW, et al. Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy. Epilepsy Research. 2007;73(1):91-101. 3. Brodie MJ, et al. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized, placebo-controlled trial. Epilepsia. 2009;50(8):1899-1909. 4. Glauser T, et al. Efficacy and safety of rufinamide adjunctive therapy in patients with Lennox-Gastaut syndrome: a randomized, double-blind, placebo-controlled trial. Epilepsia. 2008;49(4):661-668. 5. Patsalos PN. Clinical pharmacokinetics of rufinamide. Clinical Pharmacokinetics. 2013;52(6):425-436. 6. Perucca E, et al. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia. 2008;49(7):1123-1141.