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Rufinamide: Drug information

Rufinamide: Drug information
(For additional information see "Rufinamide: Patient drug information" and see "Rufinamide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Banzel
Brand Names: Canada
  • Banzel
Pharmacologic Category
  • Antiseizure Agent, Triazole Derivative
Dosing: Adult
Lennox-Gastaut syndrome

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 (Ref).

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.

Dosing: Kidney Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Older Adult

Refer to adult dosing. Initiate at the low end of the dosing range; use with caution.

Dosing: Pediatric

(For additional information see "Rufinamide: Pediatric drug information")

Lennox-Gastaut syndrome

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents:

Mild to moderate impairment: Use with caution

Severe impairment: Use is not recommended (has not been studied)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults unless otherwise specified, and may include incidences with adjunctive antiseizure therapies.

>10%:

Cardiovascular: ECG abnormality (shortened QT interval: 46% to 65%)

Gastrointestinal: Nausea (7% to 12%), vomiting (children, adolescents: 17%; adults: 5%)

Nervous system: Dizziness (3% to 19%), drowsiness (11% to 24%), fatigue (9% to 16%), headache (children, adolescents: 16%; adults: 27%)

1% to 10%:

Dermatologic: Pruritus (children, adolescents: 3%), skin rash (children, adolescents: 4%)

Gastrointestinal: Constipation (adults: 3%), decreased appetite (children, adolescents: 5%), dyspepsia (adults: 3%), increased appetite, upper abdominal pain (3%)

Genitourinary: Pollakiuria

Hematologic & oncologic: Anemia, leukopenia (4%)

Infection: Influenza (children, adolescents: 5%)

Nervous system: Abnormal gait (1% to 3%), aggressive behavior (children, adolescents: 3%), anxiety (adults: 3%), ataxia (4% to 5%), disturbance in attention (children, adolescents: 3%), psychomotor agitation (children, adolescents: 3%), status epilepticus (≤4%), tremor (adults: 6%), vertigo (adults: 3%)

Neuromuscular & skeletal: Back pain (adults: 3%)

Ophthalmic: Blurred vision (adults: 6%), diplopia (4% to 9%), nystagmus disorder (adults: 6%)

Respiratory: Bronchitis (children, adolescents: 3%), nasopharyngitis (children, adolescents: 5%), sinusitis (children, adolescents: 3%)

<1%:

Cardiovascular: First-degree atrioventricular block, right bundle branch block

Genitourinary: Dysuria, hematuria, nocturia, urinary incontinence

Hematologic & oncologic: Iron deficiency anemia, lymphadenopathy, neutropenia, thrombocytopenia

Renal: Nephrolithiasis, polyuria

Postmarketing:

Dermatologic: Stevens-Johnson syndrome (Chambel 2013)

Hematologic & oncologic: Agranulocytosis (Ide 2015)

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Shahbaz 2013)

Contraindications

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

Warnings/Precautions

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.

Warnings: Additional Pediatric Considerations

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Pricing: US

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Banzel: 100 mg, 200 mg, 400 mg

Administration: Adult

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.

Administration: Pediatric

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.

Medication Guide and/or Vaccine Information Statement (VIS)

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.

Use: Labeled Indications

Lennox-Gastaut syndrome: Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in adults and children 1 year and older

Metabolism/Transport Effects

Induces CYP3A4 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): May enhance the adverse/toxic effect of Rufinamide. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Atogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification

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 Interactions

Food increases the absorption of rufinamide. Management: Take with food.

Reproductive Considerations

Some hormonal contraceptives may be less effective with concurrent rufinamide use; additional forms of nonhormonal contraceptives should be used.

Pregnancy Considerations

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.

Breastfeeding Considerations

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.

Dietary Considerations

Take with food.

Monitoring Parameters

Serum levels of concurrent antiseizure medications; suicidality (eg, suicidal thoughts, depression, behavioral changes); rash (may indicate multi-organ hypersensitivity reactions).

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Patients undergoing dialysis 3 hours postdosing displayed a decrease in AUC and Cmax of 29% and 16%, respectively.

Sex: Population pharmacokinetic analyses of women show a 6% to 14% lower apparent Cl of rufinamide compared with men.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Banzel | Inovelon | Saikel;
  • (AT) Austria: Inovelon;
  • (AU) Australia: Inovelon;
  • (BE) Belgium: Inovelon;
  • (BG) Bulgaria: Inovelon;
  • (BR) Brazil: Inovelon;
  • (CH) Switzerland: Inovelon;
  • (CL) Chile: Inovelon;
  • (CO) Colombia: Banzel | Inovelon;
  • (DE) Germany: Inovelon;
  • (EC) Ecuador: Inovelon;
  • (EE) Estonia: Inovelon;
  • (ES) Spain: Inovelon;
  • (FI) Finland: Inovelon;
  • (FR) France: Inovelon;
  • (GB) United Kingdom: Inovelon;
  • (GR) Greece: Inovelon;
  • (HK) Hong Kong: Inovelon;
  • (HU) Hungary: Inovelon;
  • (ID) Indonesia: Inovelon;
  • (IE) Ireland: Inovelon;
  • (IT) Italy: Inovelon;
  • (JP) Japan: Inovelon;
  • (KR) Korea, Republic of: Inovelon;
  • (LT) Lithuania: Inovelon;
  • (LV) Latvia: Inovelon;
  • (MX) Mexico: Inovelon;
  • (MY) Malaysia: Inovelon;
  • (NL) Netherlands: Inovelon;
  • (NO) Norway: Inovelon;
  • (NZ) New Zealand: Inovelon;
  • (PL) Poland: Inovelon;
  • (PR) Puerto Rico: Banzel;
  • (PT) Portugal: Inovelon;
  • (RU) Russian Federation: Inovelon;
  • (SA) Saudi Arabia: Inovelon;
  • (SE) Sweden: Inovelon;
  • (SG) Singapore: Inovelon;
  • (SK) Slovakia: Inovelon;
  • (TH) Thailand: Inovelon;
  • (TW) Taiwan: Inovelon
  1. Banzel (rufinamide) [prescribing information]. Nutley, NJ: Eisai Inc; December 2022.
  2. Banzel (rufinamide) [product monograph]. Mississauga, Ontario, Canada: Eisai Ltd; October 2020.
  3. Brodie MJ, Rosenfeld WE, Vazquez B, 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. doi:10.1111/j.1528-1167.2009.02160.x [PubMed 19490053]
  4. Chambel M, Mascarenhas MI, Regala J, Gouveia C, Prates S. Clinical Stevens-Johnson syndrome and rufinamide: A clinical case. Allergol Immunopathol (Madr). 2013;41(1):68-69. doi:10.1016/j.aller.2011.12.004 [PubMed 22306278]
  5. Ide M, Kato T, Nakata M, et al. A granulocytosis associated with rufinamide: A case report. Brain Dev. 2015;37(8):825-828. doi:10.1016/j.braindev.2014.12.010 [PubMed 25619447]
  6. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  7. Refer to the manufacturer's labeling.
  8. Shahbaz S, Sivamani RK, Konia T, Burrall B. A case of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) related to rufinamide. Dermatol Online J. 2013;19(4):4. [PubMed 24021364]
  9. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  10. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
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