Rufinamide

Trade Names:
Banzel
- Tablets, oral 200 mg
- Tablets, oral 400 mg

Pharmacology

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The precise mechanism is unknown; however, modulation of the activity of sodium channels and prolongation of the inactive state of the channel is suspected to be involved.

Pharmacokinetics

Absorption

Well absorbed after oral administration. However, the bioavailability decreases as the dose increases. T _max is between 4 and 6 h. Food increases the extent of absorption 34%.

Distribution

Binding to plasma protein is 34%, predominantly to albumin (27%). Apparent Vd is 50 L at a dosage of 3,200 mg/day.

Metabolism

Extensively metabolized to inactive metabolites, primarily by carboxylesterase-mediated hydrolysis. Rufinamide is a weak inhibitor of CYP2E1 and a weak inducer of CYP3A4.

Elimination

Elimination half-life is 6 to 10 h. Renal elimination accounts for 85% of an administered dose, with less than 2% recovered unchanged.

Special Populations

Pharmacokinetics in patients with severe renal function impairment (CrCl less than 30 mL/min) are similar to those of healthy subjects. Patients undergoing dialysis 3 h postdosing displayed a decrease in AUC and C _max of 29% and 16%, respectively. Consider adjusting dose for drug loss during dialysis.

Pharmacokinetics have not been studied. Use in severe hepatic function impairment is not recommended.

Indications and Usage

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in adults and children 4 yr of age and older.

Contraindications

Patients with familial short QT syndrome.

Dosage and Administration

PO Start with 400 to 800 mg/day in 2 equally divided doses. Increase the dosage by 400 to 800 mg/day every 2 days to a max of 3,200 mg/day, given in 2 equally divided doses.

PO Start with approximately 10 mg/kg/day in 2 equally divided doses. Increase the dosage in increments of 10 mg/kg every other day to a target dosage of 45 mg/kg/day (max, 3,200 mg/day) administered in 2 equally divided doses.

PO Hemodialysis decreases exposure by about 30%. Consider adjusting the dose to account for drug loss during hemodialysis.

General Advice

• Administer with food.
• Tablets are scored on both sides and can be cut in half for dosing flexibility. Tablets can be administered whole, as half tablets, or crushed.

Storage/Stability

Store at 59° to 86°F. Protect from moisture.

Drug Interactions

Plasma concentrations may be increased by rufinamide, while rufinamide plasma concentrations may be decreased.

Carbamazepine and rufinamide plasma concentrations may be decreased.

Efficacy of hormonal contraceptives may be decreased; consider additional, non-hormonal contraception.

Plasma concentrations may be decreased by rufinamide.

Rufinamide plasma concentrations may be decreased.

Plasma concentrations may be decreased.

Rufinamide plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Observe the clinical response of the patient and adjust dosing as needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (27%); somnolence (24%); dizziness (19%); fatigue (16%); tremor (6%); ataxia, decreased appetite (5%); aggression, anxiety, disturbed attention, gait disturbances, psychomotor hyperactivity, vertigo (3%), convulsions (2%); increased appetite (at least 1%).

Dermatologic

Rash (4%); pruritus (3%).

EENT

Diplopia (9%); blurred vision, nystagmus (6%); nasopharyngitis (5%); ear infection (3%).

GI

Vomiting (17%); nausea (12%); constipation, dyspepsia (3%).

Genitourinary

Pollakiuria (at least 1%).

Hematologic-Lymphatic

Anemia (at least 1%).

Musculoskeletal

Back pain (3%).

Respiratory

Bronchitis, sinusitis (3%).

Miscellaneous

Influenza (5%); abdominal upper pain (3%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 4 yr of age.

Elderly

Select dose with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and/or concomitant disease or other drug therapy.

Renal Function

Consider dosage adjustment in patients on dialysis.

Hepatic Function

Use with caution in patients with mild to moderate hepatic function impairment. Use in patients with severe hepatic function impairment is not recommended.

CNS reactions

Ataxia, coordination abnormalities, dizziness, fatigue, gait disturbances, and somnolence have been reported.

Discontinuation

Gradually withdraw treatment by approximately 25% every 2 days to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus.

Multiorgan hypersensitivity

Has been reported rarely.

QT shortening

ECG studies demonstrated QT interval shortening (up to 20 msec). Administration is contraindicated in patients with familial short QT syndrome.

Status epilepticus

Treatment-emergent status epilepticus has been reported.

Suicide

The risk of suicidal thoughts and behavior is increased.

Overdosage

Symptoms

Experience with overdosage is limited. One patient receiving 7,200 mg/day did not exhibit major signs or symptoms and did not require medical intervention.

Patient Information

• Advise patients or caregivers to be alert for emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, the emergence of suicidal thoughts or behavior, or thoughts about self-harm, and to immediately report any behaviors of concern to health care provider.
• Instruct patients to take with food.
• Advise patients to avoid alcoholic beverages while taking this medication.
• Advise patients that this product may cause somnolence or dizziness and not to drive or operate machinery until they have gained sufficient experience to determine whether the drug adversely affects their mental and/or motor performance.
• Instruct patients to notify health care provider if they experience a rash associated with fever.
• Advise patients using oral/hormonal contraceptive to use a nonhormonal form of contraception during therapy.

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