Lennox-Gastaut syndrome (adjunctive): Oral: 400 to 800 mg/day in 2 equally divided doses; increase dose by 400 to 800 mg/day every other day to a maximum dose of 3.2 g/day in 2 equally divided doses (Brodie 2009; manufacturer’s labeling).
Discontinuation of therapy: Discontinue therapy gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Reducing dose by approximately 25% every 2 days was effective in trials.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl <30 mL/minute: No dosage adjustment necessary.
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling. However, consider dosage adjustment for loss of drug.
Mild to moderate impairment (Child-Pugh score 5 to 9): Use with caution.
Severe impairment (Child-Pugh score 10 to 15): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use is not recommended.
(For additional information see "Rufinamide: Pediatric drug information")
Lennox-Gastaut syndrome (adjunctive):
Children and Adolescents <17 years: Oral: Initial: 10 mg/kg/day in 2 equally divided doses; increase dose by ~10 mg/kg increments every other day to a target daily dose of 45 mg/kg/day in 2 equally divided doses; maximum daily dose: 3,200 mg/day; effectiveness of doses lower than the target dose is unknown.
Adolescents ≥17 years: Oral: Initial: 400 to 800 mg/day in 2 equally divided doses; increase dose by 400 to 800 mg daily every other day to a maximum daily dose of 3,200 mg/day in 2 equally divided doses; effectiveness of doses lower than 3,200 mg/day is unknown.
Discontinuation of therapy: Children and Adolescents: Discontinue therapy gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Reducing dose by approximately 25% every 2 days was effective in trials.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents:
CrCl <30 mL/minute: No dosage adjustment necessary
Hemodialysis: Dialyzable (~30%); there are no specific dosage adjustments provided in the manufacturer's labeling. However, consider dosage adjustment for loss of drug.
Children and Adolescents:
Mild to moderate impairment: Use with caution
Severe impairment: Use is not recommended (has not been studied)
Refer to adult dosing. Initiate at the low end of the dosing range; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Banzel: 40 mg/mL (460 mL) [contains methylparaben, propylene glycol, propylparaben; orange flavor]
Generic: 40 mg/mL (460 mL)
Tablet, Oral:
Banzel: 200 mg, 400 mg [scored; contains corn starch]
Generic: 200 mg, 400 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Banzel: 100 mg, 200 mg, 400 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021911s017,201367s008lbl.pdf#page=19, must be dispensed with this medication.
Oral: Administer with food. Tablets may be swallowed whole, split in half, or crushed. Oral suspension should be administered using the provided adapter and calibrated oral syringe; shake well before each dose.
Oral: Administer with food.
Tablets: May be swallowed whole, split in half, or crushed.
Oral suspension: Shake well; use provided adapter and calibrated oral syringe to measure dose.
Lennox-Gastaut syndrome: Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in adults and children 1 year and older
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Shortened QT interval (46% to 65%; dose related)
Central nervous system: Headache (adults 27%, children 16%), drowsiness (11% to 24%), dizziness (3% to 19%), fatigue (9% to 16%)
Gastrointestinal: Vomiting (children 17%, adults 5%), nausea (7% to 12%)
1% to 10%:
Central nervous system: Ataxia (4% to 5%), status epilepticus (≤4%), aggressive behavior (children 3%), anxiety (adults 3%), disturbance in attention (children 3%), hyperactivity (children 3%), vertigo (adults 3%), abnormal gait (1% to 3%), convulsions (children 2%)
Dermatologic: Skin rash (children 4%), pruritus (children 3%)
Gastrointestinal: Decreased appetite (children 5%), constipation (adults 3%), dyspepsia (adults 3%), upper abdominal pain (3%), increased appetite (≥1%)
Hematologic & oncologic: Leukopenia (4%), anemia (1%)
Infection: Influenza (children 5%)
Neuromuscular & skeletal: Tremor (adults 6%), back pain (adults 3%)
Ophthalmic: Diplopia (4% to 9%), blurred vision (adults 6%), nystagmus (adults 6%)
Otic: Otic infection (children 3%), pollakiuria (1%)
Respiratory: Nasopharyngitis (children 5%), bronchitis (children 3%), sinusitis (children 3%)
<1%, postmarketing, and/or case reports: Atrioventricular block (first degree), bundle branch block (right), dysuria, hematuria, hypersensitivity (multiorgan), iron-deficiency anemia, lymphadenopathy, nephrolithiasis, neutropenia, nocturia, polyuria, Stevens-Johnson syndrome, suicidal ideation, thrombocytopenia, urinary incontinence
Patients with familial short QT syndrome
Canadian labeling: Additional contraindications (not in US labeling): Family history of short QT syndrome; presence or history of short QT interval; hypersensitivity to rufinamide, triazole derivatives, or any component of the formulation
Concerns related to adverse effects:
• Altered cardiac conduction: Has been associated with shortening of the QT interval. Use caution in patients receiving concurrent medications that shorten the QT interval. Contraindicated in patients with familial short-QT syndrome.
• CNS effects: Use has been associated with CNS-related adverse events, most significant of these were cognitive symptoms (including somnolence or fatigue) and coordination abnormalities (including ataxia, dizziness, and gait disturbances). Caution patients about performing tasks that require mental alertness (eg, operating machinery or driving).
• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal, multiorgan hypersensitivity reactions (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Evaluate immediately if signs or symptoms are present. Discontinuation and conversion to alternate therapy may be required.
• Dermatologic reactions: Potentially serious, sometimes fatal, dermatologic reactions including Stevens-Johnson syndrome (SJS) have been reported; monitor for signs and symptoms of skin reactions; discontinuation and conversion to alternate therapy may be required.
• Leukopenia: Decreased white blood cell count has been reported during treatment.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild to moderate impairment; use in not recommended in patients with severe impairment.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Reducing dose by ~25% every two days was effective in trials.
Case reports of possibly fatal multiorgan hypersensitivity reactions (including severe hepatitis) with rufinamide occurred in children <12 years and presented within the first 4 weeks of therapy. Children may experience some adverse effects not reported in adults, including aggression, attention disturbance, hyperactivity, pruritus, rash, nasopharyngitis, and seizures.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Induces CYP3A4 (weak)
Alcohol (Ethyl): May enhance the adverse/toxic effect of Rufinamide. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
CarBAMazepine: Rufinamide may decrease the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
CNS Depressants: Rufinamide may enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Rufinamide. Rufinamide may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
LamoTRIgine: Rufinamide may enhance the arrhythmogenic effect of LamoTRIgine. LamoTRIgine may enhance the CNS depressant effect of Rufinamide. Specifically, sleepiness and dizziness may be enhanced. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Additionally, if combined, caution patients that sleepiness and dizziness may be increased. Risk D: Consider therapy modification
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
PHENobarbital: Rufinamide may increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Phenytoin: Rufinamide may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Primidone: Rufinamide may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations may be increased. Primidone may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Valproate Products: May increase the serum concentration of Rufinamide. Management: Initiate rufinamide at a dose less than 10 mg/kg/day (children) or 400 mg/day (adults) in patients receiving valproic acid. In patients receiving rufinamide, initiate valproic acid at a low dose and titrate based on clinical response. Risk D: Consider therapy modification
Food increases the absorption of rufinamide. Management: Take with food.
Some hormonal contraceptives may be less effective with concurrent rufinamide use; additional forms of nonhormonal contraceptives should be used.
Adverse effects were seen in animal reproduction studies.
Patients exposed to rufinamide during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
It is not known if rufinamide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Take with food.
Serum levels of concurrent antiseizure medications; suicidality (eg, suicidal thoughts, depression, behavioral changes); rash (may indicate multi-organ hypersensitivity reactions).
A triazole-derivative antiseizure whose exact mechanism is unknown. In vitro, it prolongs the inactive state of the sodium channels, thereby limiting repetitive firing of sodium-dependent action potentials mediating antiseizure effects.
Note: Pharmacokinetic data in pediatric patients (1 to 17 years) has been shown to be similar to adult data.
Absorption: Slow; extensive ≥85%; increased with food
Distribution: Vd: ~50 L
Protein binding: 34%, primarily to albumin (27%)
Metabolism: Extensively via carboxylesterase-mediated hydrolysis of the carboxylamide group to CGP 47292 (inactive metabolite); weak inhibitor of CYP2E1 and weak inducer of CYP3A4
Bioavailability: Extent decreased with increased dose; oral tablets and oral suspension are bioequivalent
Half-life elimination: ~6 to 10 hours
Time to peak, plasma: 4 to 6 hours
Excretion: Urine (85%, ~66% as CGP 47292, 2% as unchanged drug)
Renal function impairment: Patients undergoing dialysis 3 hours postdosing displayed a decrease in AUC and Cmax of 29% and 16%, respectively.
Gender: Population pharmacokinetic analyses of women show a 6% to 14% lower apparent Cl of rufinamide compared with men.
Suspension (Banzel Oral)
40 mg/mL (per mL): $4.59
Suspension (Rufinamide Oral)
40 mg/mL (per mL): $3.96 - $4.19
Tablets (Banzel Oral)
200 mg (per each): $15.84
400 mg (per each): $31.68
Tablets (Rufinamide Oral)
200 mg (per each): $14.24 - $15.05
400 mg (per each): $28.48 - $30.10
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