Rufinamide
Tablet, Film Coated · Oral
Uses
Rufinamide oral suspension is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults. Rufinamide oral suspension is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults ( 1 )
Dosage and administration
2 DOSAGE AND ADMINISTRATION · Rufinamide should be given with food. · Measure oral suspension using provided adapter and dosing syringe ( 2.2 ) Pediatric patients 1 year and older: · Starting daily dose: 10 mg/kg per day in two equally divided doses ( 2.1 ) · Increase by 10 mg/kg increments every other day to maximum dose of 45 mg/kg per day, not to exceed 3200 mg per day, in two divided doses ( 2.1 ) Adults: · Starting daily dose: 400-800 mg per day in two equally divided doses ( 2.1 ) · Increase by 400-800 mg every other day until a maximum dose of 3200 mg per day, in two divided doses, is reached ( 2.1 ) 2.1 Dosage Information Pediatric patients (1 year to less than 17 years) The recommended starting daily dose of rufinamide in pediatric patients with Lennox-Gastaut Syndrome is approximately 10 mg/kg administered in two equally divided doses. The dose should be increased by approximately 10 mg/kg increments every other day until a maximum daily dose of 45 mg/kg, not to exceed 3200 mg, administered in two equally divided doses, is reached. It is not known whether doses lower than the target doses are effective. Adults (17 years and older) The recommended starting daily dose of rufinamide in adults with Lennox-Gastaut Syndrome is 400 to 800 mg per 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, administered in two equally divided doses, is reached. It is not known whether doses lower than 3200 mg are effective. 2.2 Administration Information Administer rufinamide with food. Rufinamide 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 The dosing syringe should be inserted into the adapter and the dose withdrawn from the inverted bottle.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 Patient Counseling Information (17)]. 2.3 Dosing in Patients Undergoing Hemodialysis Hemodialysis may reduce exposure to a limited (about 30%) extent. Accordingly, adjusting the rufinamide dose during the dialysis process should be considered [see Clinical Pharmacology (12.3)]. 2.4 Dosing in Patients with Hepatic Disease Use of rufinamide 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 Populations (8.7) ]. 2.5 Dosing in Patients Taking Valproate Patients taking valproate should begin rufinamide at a dose lower than 10 mg/kg per day in pediatric patients or 400 mg per day in adults [see Drug Interactions (7.2)].
Dosage forms and strengths
Oral suspension: 40 mg/mL. · Oral suspension: 40 mg/mL ( 3 )
Contraindications
Rufinamide is contraindicated in patients with Familial Short QT syndrome [see Warnings and Precautions (5.3)]. Rufinamide is contraindicated in patients with Familial Short QT syndrome ( 4 )
Warnings and precautions
• Monitor patients for new or worsening depression, suicidal thoughts/behavior, and unusual changes in mood or behavior ( 5.1 )
• Central nervous system reactions can occur ( 5.2 )
• Use caution when administering rufinamide with other drugs that shorten the QT interval ( 5.3 )
• Discontinue rufinamide if multi-organ hypersensitivity reaction occurs ( 5.4 )
• Withdraw rufinamide gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus ( 5.5 ) 5.1 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including rufinamide, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1: Absolute and Relative Risk of Suicidal Behavior and Ideation Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing rufinamide or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. 5.2 Central Nervous System Reactions Use of rufinamide has been associated with central nervous system-related adverse reactions in the controlled clinical trial of patients 4 years or older with Lennox-Gastaut Syndrome. The most significant of these can be classified into two general categories: 1) somnolence or fatigue, and 2) coordination abnormalities, dizziness, gait disturbances, and ataxia. Somnolence was reported in 24% of rufinamide -treated patients compared to 13% of patients on placebo, and led to study discontinuation in 3% of rufinamide -treated patients compared to 0% of patients on placebo. Fatigue was reported in 10% of rufinamide -treated patients compared to 8% of patients on placebo. It led to study discontinuation in 1% of rufinamide -treated patients and 0% of patients on placebo. Dizziness was reported in 2.7% of rufinamide -treated patients compared to 0% of patients on placebo, and did not lead to study discontinuation. Ataxia and gait disturbance were reported in 5.4% and 1.4% of rufinamide -treated patients, respectively, compared to no patient on placebo. None of these reactions led to study discontinuation. Accordingly, patients should be advised not to drive or operate machinery until they have gained sufficient experience on rufinamide to gauge whether it adversely affects their ability to drive or operate machinery. 5.3 QT Shortening Formal cardiac ECG studies demonstrated shortening of the QT interval (mean = 20 msec, for doses more than or equal to 2400 mg twice daily) with rufinamide. In a placebo-controlled study of the QT interval, a higher percentage of rufinamide -treated subjects (46% at 2400 mg, 46% at 3200 mg, and 65% at 4800 mg) had a QT shortening of greater than 20 msec at T max compared to placebo (5-10%). Reductions of the QT interval below 300 msec were not observed in the formal QT studies with doses up to 7200 mg per day. Moreover, there was no signal for drug-induced sudden death or ventricular arrhythmias. The degree of QT shortening induced by rufinamide is without any known clinical risk. Familial Short QT syndrome is associated with an increased risk of sudden death and ventricular arrhythmias, particularly ventricular fibrillation.
Side effects
The following serious adverse reactions are described below and elsewhere in the labeling: · Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)] · Central Nervous System Reactions [see Warnings and Precautions (5.2)] · QT Shortening [see Warnings and Precautions (5.3)] · Multi-Organ Hypersensitivity/Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)] · Leukopenia [see Warnings and Precautions (5.7)] Most common adverse reactions (≥ 10% and greater than placebo) were headache, dizziness, fatigue, somnolence, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adult and Pediatric Patients ages 3 to 17 years of age In the pooled, double-blind, adjunctive therapy studies in adult and pediatric patients ages 3 to 17 years of age, the most common (≥ 10%) adverse reactions in rufinamide-treated patients, in all doses studied (200 to 3200 mg per day) with a higher frequency than in patients on placebo were: headache, dizziness, fatigue, somnolence, and nausea. Table 2 lists adverse reactions that occurred in at least 3% of pediatric patients (ages 3 to less than 17 years) with epilepsy treated with rufinamide in controlled adjunctive studies and were numerically more common in patients treated with rufinamide than in patients on placebo. At the target dose of 45 mg/kg per day for adjunctive therapy in pediatric patients (ages 3 to less than 17 years), the most common (≥ 3%) adverse reactions with an incidence greater than in placebo for rufinamide were somnolence, vomiting, and headache. Table 2: Adverse Reactions in Pediatric Patients (Ages 3 to less than 17 years) in Pooled Double-Blind Adjunctive Trials Adverse Reaction Rufinamide (N=187) % Placebo (N=182) % Somnolence 17 9 Vomiting 17 7 Headache 16 8 Fatigue 9 8 Dizziness 8 6 Nausea 7 3 Influenza 5 4 Nasopharyngitis 5 3 Decreased Appetite 5 2 Rash 4 2 Ataxia 4 1 Diplopia 4 1 Bronchitis 3 2 Sinusitis 3 2 Psychomotor Hyperactivity 3 1 Upper Abdominal Pain 3 2 Aggression 3 2 Ear Infection 3 1 Disturbance in Attention 3 1 Pruritis 3 0 Table 3 lists adverse reactions that occurred in at least 3% of adult patients with epilepsy treated with rufinamide (up to 3200 mg per day) in adjunctive controlled studies and were numerically more common in patients treated with rufinamide than in patients on placebo. In these studies, either rufinamide or placebo was added to the current AED therapy. At all doses studied of up to 3200 mg per day given as adjunctive therapy in adults, the most common (≥ 3%) adverse reactions, and with the greatest increase in incidence compared to placebo, for rufinamide were dizziness, fatigue, nausea, diplopia, vision blurred, and ataxia. Table 3: Adverse Reactions in Adults in Pooled Double-Blind Adjunctive Trials Adverse Reaction Rufinamide (N=823) % Placebo (N=376) % Headache 27 26 Dizziness 19 12 Fatigue 16 10 Nausea 12 9 Somnolence 11 9 Diplopia 9 3 Tremor 6 5 Nystagmus 6 5 Blurred Vision 6 2 Vomiting 5 4 Ataxia 4 0 Upper Abdominal Pain 3 2 Anxiety 3 2 Constipation 3 2 Dyspepsia 3 2 Back Pain 3 1 Gait Disturbance 3 1 Vertigo 3 1 Discontinuation in Controlled Clinical Studies In controlled, double-blind, adjunctive clinical studies, 9% of pediatric and adult patients receiving rufinamide as adjunctive therapy and 4% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of rufinamide (greater than 1%) used as adjunctive therapy were generally similar in adults and pediatric patients. In pediatric patients (ages 4 to less than 17 years) double-blind adjunctive clinical studies, 8% of patients receiving rufinamide as adjunctive therapy (at the recommended dose of 45 mg/kg per day) and 2% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of rufinamide (greater than 1%) used as adjunctive therapy are presented in Table 4. Table 4: Most Common Adverse Reactions Leading to Discontinuation in Pediatric Patients (Ages 4 to less than 17 years) in Pooled Double-Blind Adjunctive Trials Adverse Reaction Rufinamide (N=187) % Placebo (N=182) % Convulsion 2 1 Rash 2 1 Fatigue 2 0 Vomiting 1 0 In adult double-blind, adjunctive clinical studies, 10% of patients receiving rufinamide as adjunctive therapy (at doses up to 3200 mg per day) and 6% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of rufinamide (greater than 1%) used as adjunctive therapy are presented in Table 5. Table 5: Most Common Adverse Reactions Leading to Discontinuation in Adult Patients in Pooled Double-Blind Adjunctive Trials Adverse Reaction Rufinamide (N=823) % Placebo (N=376) % Dizziness 3 1 Fatigue 2 1 Headache 2 1 Nausea 1 0 Ataxia 1 0 Pediatric Patients ages 1 to less than 4 years In a multicenter, parallel group, open-label study comparing rufinamide (45 mg/kg per day) adjunctive treatment (n=25) to the adjunctive treatment with an AED of the investigator’s choice (n=11) in pediatric patients (1 year to less than 4 years of age) with inadequately controlled Lennox-Gastaut Syndrome, the adverse reaction profile was generally similar to that observed in adults and pediatric patients 4 years of age and older treated with rufinamide.
Drug interactions
• Patients on valproate should begin at a rufinamide dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults) ( 7.2 )
• Hormonal contraceptives may be less effective with rufinamide; use additional non-hormonal forms of contraception ( 7.3 ) 7.1 Effects of Rufinamide on other AEDs Population pharmacokinetic analysis of average concentration at steady state of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, and valproate showed that typical rufinamide C avss levels had little effect on the pharmacokinetics of other AEDs. Any effects, when they occur, have been more marked in the pediatric population. Table 6 summarizes the drug-drug interactions of rufinamide with other AEDs. Table 6: Summary of drug-drug interactions of rufinamide with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase by 8 to 13% b) Decrease by 25 to 46% c), d) Independent of dose or concentration of phenobarbital Phenytoin Increase by 7 to 21% b) Decrease by 25 to 46% c), d) Independent of dose or concentration of phenytoin Topiramate No Effect No Effect Valproate No Effect Increase by <16 to 70% c) Dependent on concentration of valproate Primidone Not Investigated Decrease by 25 to 46% c), d ) Independent of dose or concentration of primidone Benzodiazepines e) Not Investigated No Effect a) Predictions are based on rufinamide concentrations at the maximum recommended dose of rufinamide. b) Maximum changes predicted to be in pediatric patients and in adult patients who achieve significantly higher levels of rufinamide, as the effect of rufinamide on these AEDs is concentration-dependent. c) Larger effects in pediatric patients at high doses/concentrations of AEDs. d) Phenobarbital, primidone and phenytoin were treated as a single covariate (phenobarbital-type inducers) to examine the effect of these agents on rufinamide clearance. e) All compounds of the benzodiazepine class were pooled to examine for ‘class effect’ on rufinamide clearance. Phenytoin: The decrease in clearance of phenytoin estimated at typical levels of rufinamide (C avss 15 µg/mL) is predicted to increase plasma levels of phenytoin by 7 to 21%. As phenytoin is known to have non-linear pharmacokinetics (clearance becomes saturated at higher doses), it is possible that exposure will be greater than the model prediction. 7.2 Effects of other AEDs on Rufinamide Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of rufinamide (see Table 6). Given that the majority of clearance of rufinamide is via a non-CYP-dependent route, the observed decreases in blood levels seen with carbamazepine, phenytoin, phenobarbital, and primidone are unlikely to be entirely attributable to induction of a P450 enzyme. Other factors explaining this interaction are not understood. Any effects, where they occurred, were likely to be more marked in the pediatric population. Valproate Patients stabilized on rufinamide before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose. Similarly, patients on valproate should begin at a rufinamide dose lower than 10 mg/kg per day (pediatric patients) or 400 mg per day (adults) [ see Dosage and Administration (2.5), Clinical Pharmacology (12.3) ]. 7.3 Effects of Rufinamide on Hormonal Contraceptives Female patients of childbearing age should be warned that the concurrent use of rufinamide with hormonal contraceptives may render this method of contraception less effective. Additional non-hormonal forms of contraception are recommended when using rufinamide [see Use in Specific Populations (8.3) , Clinical Pharmacology (12.3 ) and Patient Counseling Information (17)].
Use in specific populations
• Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 )
• Renal impairment: Consider adjusting the rufinamide dose for the loss of drug upon dialysis ( 8.6 )
• Not recommended in patients with severe hepatic impairment ( 8.7 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as rufinamide, during pregnancy. Encourage women who are taking rufinamide during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary There are no adequate data on the developmental risks associated with use of rufinamide in pregnant women. In animal reproduction studies, oral administration of rufinamide resulted in developmental toxicity in pregnant rats and rabbits at clinically relevant doses [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal data Oral administration of rufinamide (0, 20, 100, or 300 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal weight and increased incidence of fetal skeletal abnormalities at 100 and 300 mg/kg/day, which were associated with maternal toxicity. The maternal plasma exposure (AUC) at the no-adverse effect dose (20 mg/kg/day) for developmental toxicity was less than that in humans at the maximum recommended human dose (MRHD) of 3200 mg/day. Oral administration of rufinamide (0, 30, 200, or 1000 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in embryofetal death, decreased fetal body weight, and increased incidence of fetal visceral and skeletal abnormalities at doses of 200 and 1000 mg/kg/day. The high dose (1000 mg/kg/day) was associated with abortion. Plasma exposure (AUC) at the no-adverse effect dose (30 mg/kg/day) was less than that in humans at the MRHD. When rufinamide was orally administered (0, 5, 30, or 150 mg/kg/day) to pregnant rats throughout pregnancy and lactation, decreased offspring growth and survival were observed at all doses tested. A no-effect dose for adverse effects on pre- and postnatal development was not established. At the lowest dose tested (5 mg/kg/day), plasma exposure (AUC) was less than that in humans at the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of rufinamide in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for rufinamide and any potential adverse effects on the breastfed infant from rufinamide or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Contraception Use of rufinamide may reduce the effectiveness of hormonal contraceptives containing ethinyl estradiol or norethindrone. Advise women of reproductive potential taking rufinamide who are using a contraceptive containing ethinyl estradiol and norethindrone to use an additional non-hormonal form of contraception [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ]. Infertility The effect of rufinamide on fertility in humans has not been established. Oral administration of rufinamide (20, 60, 200, and 600 mg/kg/day) to male and female rats prior to mating, during mating, and during early gestation (females only) resulted in the impairment of fertility at all dose levels tested. The no-effect dose was not established. The plasma exposure level at 20 mg/kg was approximately 0.2 times the human plasma AUC at the MRHD [see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use Safety and effectiveness have been established in pediatric patients 1 to 17 years of age. The effectiveness of rufinamide in pediatric patients 4 years of age and older was based upon an adequate and well-controlled trial of rufinamide that included both adults and pediatric patients, 4 years of age and older, with Lennox-Gastaut Syndrome. The effectiveness in patients 1 to less than 4 years was based upon a bridging pharmacokinetic and safety study [see Dosage and Administration (2.1) , Adverse Reactions (6.1) , and Clinical Studies (14)] . The pharmacokinetics of rufinamide in the pediatric patients, ages 1 to less than 4 years of age is similar to children older than 4 years of age and adults [ see Clinical Pharmacology (12.3)] . Safety and effectiveness in pediatric patients below the age of 1 year has not been established. Oral administration of rufinamide (0, 15, 50, or 150 mg/kg) to young rats for 10 weeks starting on postnatal day 7 resulted in decreased brain weights at the mid and high doses and neurobehavioral impairment (learning and memory deficit, altered startle response, decreased locomotor activity) and decreased growth (decreased body weight) at the highest dose tested. The no-effect dose for adverse effects on postnatal development in rats (15 mg/kg) was associated with a plasma exposure (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 3200 mg/day. 8.5 Geriatric Use Clinical studies of rufinamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Pharmacokinetics of rufinamide in the elderly are similar to that in the young subjects [see Clinical Pharmacology (12.3)] .
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as rufinamide, during pregnancy. Encourage women who are taking rufinamide during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary There are no adequate data on the developmental risks associated with use of rufinamide in pregnant women. In animal reproduction studies, oral administration of rufinamide resulted in developmental toxicity in pregnant rats and rabbits at clinically relevant doses [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal data Oral administration of rufinamide (0, 20, 100, or 300 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal weight and increased incidence of fetal skeletal abnormalities at 100 and 300 mg/kg/day, which were associated with maternal toxicity. The maternal plasma exposure (AUC) at the no-adverse effect dose (20 mg/kg/day) for developmental toxicity was less than that in humans at the maximum recommended human dose (MRHD) of 3200 mg/day. Oral administration of rufinamide (0, 30, 200, or 1000 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in embryofetal death, decreased fetal body weight, and increased incidence of fetal visceral and skeletal abnormalities at doses of 200 and 1000 mg/kg/day. The high dose (1000 mg/kg/day) was associated with abortion. Plasma exposure (AUC) at the no-adverse effect dose (30 mg/kg/day) was less than that in humans at the MRHD. When rufinamide was orally administered (0, 5, 30, or 150 mg/kg/day) to pregnant rats throughout pregnancy and lactation, decreased offspring growth and survival were observed at all doses tested. A no-effect dose for adverse effects on pre- and postnatal development was not established. At the lowest dose tested (5 mg/kg/day), plasma exposure (AUC) was less than that in humans at the MRHD.
Pediatric use
8.4 Pediatric Use Safety and effectiveness have been established in pediatric patients 1 to 17 years of age. The effectiveness of rufinamide in pediatric patients 4 years of age and older was based upon an adequate and well-controlled trial of rufinamide that included both adults and pediatric patients, 4 years of age and older, with Lennox-Gastaut Syndrome. The effectiveness in patients 1 to less than 4 years was based upon a bridging pharmacokinetic and safety study [see Dosage and Administration (2.1) , Adverse Reactions (6.1) , and Clinical Studies (14)] . The pharmacokinetics of rufinamide in the pediatric patients, ages 1 to less than 4 years of age is similar to children older than 4 years of age and adults [ see Clinical Pharmacology (12.3)] . Safety and effectiveness in pediatric patients below the age of 1 year has not been established. Oral administration of rufinamide (0, 15, 50, or 150 mg/kg) to young rats for 10 weeks starting on postnatal day 7 resulted in decreased brain weights at the mid and high doses and neurobehavioral impairment (learning and memory deficit, altered startle response, decreased locomotor activity) and decreased growth (decreased body weight) at the highest dose tested. The no-effect dose for adverse effects on postnatal development in rats (15 mg/kg) was associated with a plasma exposure (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 3200 mg/day.
Geriatric use
8.5 Geriatric Use Clinical studies of rufinamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Pharmacokinetics of rufinamide in the elderly are similar to that in the young subjects [see Clinical Pharmacology (12.3)] .
Overdosage
Because strategies for the management of overdose are continually evolving, it is advisable to contact a Certified Poison Control Center to determine the latest recommendations for the management of an overdose of any drug. One overdose of 7200 mg per day rufinamide was reported in an adult during the clinical trials. The overdose was associated with no major signs or symptoms, no medical intervention was required, and the patient continued in the study at the target dose. Treatment or Management of Overdose: There is no specific antidote for overdose with rufinamide. If clinically indicated, elimination of unabsorbed drug should be attempted by induction of emesis or gastric lavage. Usual precautions should be observed to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Hemodialysis: Standard hemodialysis procedures may result in limited clearance of rufinamide. Although there is no experience to date in treating overdose with hemodialysis, the procedure may be considered when indicated by the patient’s clinical state.
Description
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 C 10 H 8 F 2 N 4 O and a molecular weight of 238.2. The drug substance is a white to off white colour powder. Rufinamide is slightly soluble in tetrahydrofuran and in methanol; very slightly soluble in alcohol and in acetonitrile; practically insoluble in water. Rufinamide is available for oral administration as a liquid containing rufinamide at a concentration of 40 mg/mL. Inactive ingredients include citric acid anhydrous, colloidal silicon dioxide, hydroxyethylcellulose, hypromellose, lactose monohydrate, methylparaben, magnesium stearate, microcrystalline cellulose (GR101), microcrystalline cellulose and carboxymethylcellulose sodium, noncrystallizing sorbitol solution 70%, orange flavor, potassium sorbate, propylene glycol, propyl paraben, purified water and simethicone emulsion 30%. ruf-api
Mechanism of action
12.1 Mechanism of Action The precise mechanism(s) by which rufinamide exerts its antiepileptic effect is unknown. 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 (EC 50 of 3.8 μM).
How supplied
16.1 How Supplied Rufinamide oral suspension is an orange flavored liquid supplied in a polyethylene terephthalate (PET) bottle with child-resistant closure. The oral suspension is packaged with a dispenser set which contains a calibrated oral dosing syringe and an adapter. Store the oral suspension in an upright position. Use within 90 days of first opening the bottle, then discard any remainder. The oral suspension is available in bottles of 460 mL (NDC 67877-673-62). 16.2 Storage and Handling Store the oral suspension at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Replace cap securely after opening. The cap fits properly in place when the adapter is in place.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Administration Information · Advise patients to take rufinamide with food [see Dosage and Administration (2.2 )]. · Advise patients who are prescribed the oral suspension to shake the bottle vigorously before every administration and to use the adaptor and oral dosing syringe [see Dosage and Administration (2.2)]. Suicidal Thinking and Behavior Inform patients, their caregivers, and families that antiepileptic drugs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.1)]. Central Nervous System Reactions Inform patients about the potential for somnolence or dizziness and advise them not to drive or operate machinery until they have gained sufficient experience on rufinamide to gauge whether it adversely affects their mental and/or motor performance [see Warnings and Precautions (5.2)]. Multi-Organ Hypersensitivity Reactions Advise patients to notify their physician if they experience a rash associated with fever [see Warnings and Precautions (5.4)]. Drug Interactions Inform female patients of childbearing age that the concurrent use of rufinamide with hormonal contraceptives may render this method of contraception less effective. Recommend patients use additional non-hormonal forms of contraception when using rufinamide [see Drug Interactions (7.3) and Use in Specific Populations (8.3) ]. Inform patients that alcohol in combination with rufinamide may cause additive central nervous system effects. Pregnancy Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy. Encourage patients to enroll in the North American Antiepileptic Drug Pregnancy Registry if they become pregnant. To enroll, patients can call the toll free number 1-888-233-2334 [see Use in Specific Populations (8.1) ]. Breast-feeding Advise patients to notify their physician if they are breast-feeding or intend to breast-feed [see Use in Specific Populations (8.2) ]. Manufactured by: Alkem Laboratories Ltd., Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Bedminster, NJ 07921 Revised: 4/2026
Label text from the FDA structured product label by Ascend Laboratories, LLC (revised Aug 7, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Rufinamide in 21 products
Rufinamide NDC products (21)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60687-824 | Rufinamide 40 mg/mL Suspension | American Health Packaging | ANDA |
| 67877-673 | Rufinamide 40 mg/mL Suspension | Ascend Laboratories, LLC | ANDA |
| 59651-563 | Rufinamide 40 mg/mL Suspension | Aurobindo Pharma Limited | ANDA |
| 59651-616 | Rufinamide 200 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 59651-617 | Rufinamide 400 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 69452-223 | Rufinamide 40 mg/mL Suspension | Bionpharma Inc. | ANDA |
| 31722-598 | Rufinamide 200 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-599 | Rufinamide 400 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-688 | Rufinamide 40 mg/mL Suspension | Camber Pharmaceuticals, Inc. | ANDA |
| 68462-714 | Rufinamide 400 mg/1 Tablet, Film Coated | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-713 | Rufinamide 200 mg/1 Tablet, Film Coated | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 0054-0426 | Rufinamide 400 mg/1 Tablet, Film Coated | Hikma Pharmaceuticals USA Inc. | ANDA |
| 0054-0528 | Rufinamide 40 mg/mL Suspension | Hikma Pharmaceuticals USA Inc. | ANDA |
| 0054-0425 | Rufinamide 200 mg/1 Tablet, Film Coated | Hikma Pharmaceuticals USA Inc. | ANDA |
| 68180-797 | Rufinamide 40 mg/mL Suspension | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-803 | Rufinamide 200 mg/1 Tablet, Film Coated | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-804 | Rufinamide 400 mg/1 Tablet, Film Coated | Lupin Pharmaceuticals, Inc. | ANDA |
| 42571-392 | Rufinamide 400 mg/1 Tablet | Micro Labs Limited | ANDA |
| 42571-391 | Rufinamide 200 mg/1 Tablet | Micro Labs Limited | ANDA |
| 72603-261 | Rufinamide 40 mg/mL Suspension | NorthStar RxLLC | ANDA |
| 72205-038 | Rufinamide 40 mg/mL Suspension | Novadoz Pharmaceuticals LLC | ANDA |
Rufinamide recalls
- D-0323-2025 Apr 16, 2025 · Class II · Ongoing
CGMP Deviations - D-1087-2023 Aug 30, 2023 · Class II · Terminated
cGMP deviations: Batch was released prior to approval. - D-1088-2023 Aug 30, 2023 · Class II · Terminated
cGMP deviations: Batch was released prior to approval.
Frequently asked questions
What is Rufinamide used for?
Rufinamide oral suspension is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in pediatric patients 1 year of age and older and in adults. Rufinamide oral suspension is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults ( 1 )
What are the side effects of Rufinamide?
The following serious adverse reactions are described below and elsewhere in the labeling: · Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)] · Central Nervous System Reactions [see Warnings and Precautions (5.2)] · QT Shortening [see Warnings and Precautions (5.3)] · Multi-Organ Hypersensitivity/Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and… See the full label for the complete list.
Who makes Rufinamide?
Rufinamide is listed by 11 labelers in the FDA NDC directory, including American Health Packaging, Ascend Laboratories, LLC, Aurobindo Pharma Limited, Bionpharma Inc..
Has Rufinamide been recalled?
The FDA enforcement database lists 3 recalls for Rufinamide, most recently D-0323-2025 (class ii): CGMP Deviations