Rufinamide is a triazole derivative that is unrelated to currently marketed anticonvulsants. Although rufinamide is only FDA-approved for use in Lennox-Gastaut syndrome, clinical trial data indicate the drug may also be beneficial as adjunctive treatment of refractory partial seizures. Rufinamide was FDA-approved in November 2008 with an orphan drug designation for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. In February 2015, this indication was expanded to include children as young as 1 year of age.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
A MedGuide that provides information about the proper use and risks of rufinamide should be dispensed with each new prescription and refill. The MedGuide also discusses the risk of suicidal thoughts and behaviors associated with the use of anticonvulsant medications.
Route-Specific Administration
Oral Administration
-Administer all dosage forms orally with food.
Oral Solid Formulations
-Tablets may be administered whole, crushed, or halved. Give with food.
Oral Liquid Formulations
Oral Suspension:
-Shake well before every use.
-Administer with the provided adapter and calibrated oral dosing syringe. Insert adapter firmly into the neck of the bottle before use and keep in place for the duration of the bottle usage.
-The dosing syringe should be inserted into the adapter and the dose withdrawn from the inverted bottle.
-Replace cap after each use. The cap fits properly when the adapter is in place.
-Use within 90 days of first opening the bottle, then discard any remaining amount.
-Give with food.
Anticonvulsants, including rufinamide, are thought to carry an increased risk of suicidal ideation and behavior. An analysis by the FDA of previously gathered drug data showed that patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions. Age was not a determining factor. The increased risk of suicidal ideation and behavior occurred between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for altered mood, emerging or worsening suicidal thoughts/behavior, or depression. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior.
During clinical trials of rufinamide as adjunct therapy in Lennox-Gastaut syndrome, the following centrally-mediated adverse reactions occurred more frequently in adult and pediatric patients >= 3 years receiving rufinamide than placebo: drowsiness (24% vs. 13%), dizziness (2.7% vs. 0%), ataxia (5.4% vs. 0%), fatigue (10% vs. 8%), and gait disturbance (1.4% vs. 0%). Drowsiness and fatigue led to drug discontinuation in 3% and 1% of rufinamide-treated patients, respectively, compared to none in the placebo group. Adverse reactions occurring in double-blind adjunctive therapy studies in adults with epilepsy and more frequently than placebo included headache (27% vs. 26%), dizziness (19% vs. 12%), fatigue (16% vs. 10%), drowsiness (11% vs. 9%), tremor (6% vs. 5%), nystagmus (6% vs. 5%), ataxia (4% vs. 0%), anxiety (3% vs. 2%), gait disturbance (3% vs. 1%), and vertigo (3% vs. 1%). In adult patients, discontinuation occurred due to dizziness (3%), fatigue (2%), headache (2%), and ataxia (1%). Treatment-emergent CNS effects reported in at least 3% of pediatric patients (3-16 years of age) with epilepsy during clinical trials and with an incidence greater than placebo included drowsiness (17% vs. 9%), headache (16% vs. 8%), fatigue (9% vs. 8%), dizziness (8% vs. 6%), ataxia (4% vs. 1%), psychomotor hyperactivity (3% vs. 1%), aggression (3% vs. 2%), and disturbance in attention (3% vs. 1%). Drowsiness (16%) was also reported with a higher frequency than in the comparator group in open-label pediatric studies in children < 4 years. Adverse reactions leading to discontinuation of rufinamide versus placebo in pediatric patients (4-16 years of age) included seizures (2% vs. 1%) and fatigue (2% vs. 0%). During adjunctive therapy trials in adults, adverse CNS effects leading to discontinuation of rufinamide versus placebo included dizziness (3% vs. 1%), fatigue (2% vs. 1%), headache (2% vs. 1%), and ataxia (1% vs. 0%). Status epilepticus occurred in 4.1% of patients treated with rufinamide compared to none in the placebo group during a clinical trial for Lennox-Gastaut syndrome. During clinical trials of various seizure types, status epilepticus occurred in 0.9% of patients treated with rufinamide compared to none of those receiving placebo.
During double-blind adjunctive therapy studies, nausea/vomiting occurred more frequently in adult patients with epilepsy treated with rufinamide than those on placebo (12%/5% vs. 9%/4%). Other gastrointestinal (GI) effects occurring more frequently with rufinamide than placebo included upper abdominal pain (3% vs. 2%), constipation (3% vs. 2%), and dyspepsia (3% vs. 2%). In adults, nausea resulted in discontinuation of rufinamide in 1% of patients compared to none of those receiving placebo. Treatment-emergent GI effects reported in at least 3% of pediatric patients (3-16 years) with epilepsy during clinical trials and with an incidence greater than placebo included vomiting (17% vs. 7%), nausea (7% vs. 3%), upper abdominal pain (3% vs. 2%), and decreased appetite (5% vs. 2%). Vomiting (24%), constipation (12%), decreased appetite/anorexia (12%), weight loss (8%), and gastroenteritis (8%) were reported with a higher frequency than in the comparator group in open-label pediatric studies in children < 4 years. In pediatrics (4-16 years), vomiting resulted in discontinuation of rufinamide in 1% of patients compared to none of those receiving placebo. During other clinical trial evaluations, appetite stimulation and decreased appetite/anorexia occurred in at least 1% of study patients during clinical trials, although causality to the drug has not been established. Weight loss has been reported during post-marketing experience with rufinamide both in the presence and absence of gastrointestinal symptoms.
During double-blind adjunctive therapy studies, back pain occurred more frequently in adult patients with epilepsy treated with rufinamide than those who received placebo (3% vs. 1%).
Ophthalmic effects occurring in at least 3% of adults with epilepsy receiving rufinamide during clinical trials and with a higher frequency than placebo included diplopia (9% vs. 3%) and blurred vision (6% vs. 2%). Diplopia was reported in 4% of pediatric patients (3-16 years) with epilepsy receiving rufinamide as adjunct therapy during clinical trials and with an incidence greater than placebo (1%).
Treatment-emergent respiratory effects or infections reported in at least 3% of pediatric patients (3-16 years) with epilepsy during clinical trials who were treated with rufinamide as adjunct therapy and with an incidence greater than placebo included pharyngitis (nasopharyngitis 5% vs. 3%), bronchitis (3% vs. 2%), sinusitis (3% vs. 2%), ear infection (3% vs. 1%), and influenza (5% vs. 4%). Bronchitis (12%), cough (12%), otitis media (8%), pneumonia (8%), nasal congestion (8%), and aspiration pneumonia (8%) were reported with a higher frequency than in the comparator group in open-label pediatric studies in children < 4 years.
Pollakiuria occurred in at least 1% of study patients during clinical trials, although causality to rufinamide has not been established. Other genitourinary effects observed in 0.1-1% of study patients included hematuria, nephrolithiasis, urinary incontinence, dysuria, polyuria, enuresis, and nocturia.
Anemia occurred in at least 1% of study patients during all epilepsy clinical trials with rufinamide. Neutropenia, iron deficiency anemia, lymphadenopathy, leukopenia, and thrombocytopenia were observed in 0.1-1% of patients. In all controlled trials, leukopenia occurred in 3.7% of rufinamide-treated patients and 1.2% of placebo-treated patients. A causal relationship between these hematologic/lymphatic system disorders and rufinamide has not been established.
Stevens-Johnson syndrome and other skin rashes with mucosal involvement have been observed postmarketing with rufinamide. In a case of a 13-year-old with West syndrome, rufinamide 600 mg twice daily was added as adjunctive treatment for seizures. Within 2 weeks, the patient developed aphthous ulcers on the lips and oral mucosa, followed by fever, facial swelling, gingivostomatits with hemorrhagic plaques, conjunctival injection, and maculopapular rash on the limbs, palms, soles, back, and face. She also had 2 larger cutaneous lesions (15-20 cm diameter) on the neck and arm with erythema and edema. Despite treatment with antifungal agents and antibiotics, the condition worsened. Rufinamide was then discontinued after a diagnosis of Stevens-Johnson syndrome was suspected. A clear improvement in patient condition was noted 6 days later. If a diagnosis of Stevens-Johnson syndrome is suspected, rufinamide should be discontinued immediately. Other adverse effects reported in at least 3% of pediatric patients (3-16 years) with epilepsy during clinical trials who were treated with rufinamide as adjunct therapy and with an incidence greater than placebo included rash (unspecified) (4% vs. 2%) and pruritus (3% vs. 0%). Rash (12%) was also reported with a higher frequency than in the comparator group in an open-label pediatric study in children < 4 years. In pediatric clinical trials (4-16 years), rash (unspecified) resulted in discontinuation of rufinamide in 2% of patients vs. 1% of those receiving placebo.
Multi-organ hypersensitivity syndrome, also known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (e.g., rash, urticaria, facial edema, fever, lymphadenopathy, eosinophilia, stupor, and hepatitis) was observed in pediatric patients < 12 years of age during clinical trials and within the first 4 weeks of treatment initiation. These cases improved or resolved with rufinamide discontinuation. DRESS has also been reported during post-marketing surveillance in adults and children. If DRESS is suspected, immediately discontinue rufinamide and evaluate the patient. Initiate treatment with an alternative agent.
Right bundle-branch block and first degree AV block were reported in 0.1% to 1% of patients during rufinamide clinical trials. A higher percentage of subjects who took rufinamide during placebo-controlled clinical trials had a shortened QT interval by more than 20 milliseconds (46% at 2,400 mg, 46% at 3,200 mg, and 65% at 4,800 mg) compared to placebo (5% to 10%). Reductions in the QT interval below 300 milliseconds were not observed with rufinamide doses up to 7,200 mg/day.
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 infertility at all doses. 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.
Rufinamide is contraindicated in patients who have demonstrated rufinamide-hypersensitivity. A case of multi-organ hypersensitivity syndrome (e.g., rash, urticaria, facial edema, fever, eosinophilia, stupor, and hepatitis) was observed in one patient during clinical trials. Other possible cases were observed in pediatric patients less than 12 years of age within 4 weeks of treatment initiation. If a multi-organ hypersensitivity reaction is suspected, rufinamide should be discontinued. Patients should be instructed to promptly report potential signs of multi-organ hypersensitivity reactions, such as fever or rash, to their health care provider. All patients who develop a rash during treatment with rufinamide should be closely monitored.
In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants like rufinamide to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (>= 5 years of age). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2-2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this risk is considered to be a class effect. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for emerging or worsening suicidal thoughts/behavior or depression. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.
Rufinamide is contraindicated for use in patients with familial short QT syndrome. A higher percentage of subjects who took rufinamide during placebo-controlled clinical trials had a QT interval shortening of more than 20 milliseconds compared to placebo. Reductions in the QT interval below 300 milliseconds were not observed with rufinamide doses up to 7,200 mg/day. Familial short QT syndrome is associated with an increased risk of sudden death and ventricular arrhythmias, particularly ventricular fibrillation, which are believed to occur primarily when the corrected QT interval falls below 300 milliseconds. Nonclinical data also indicate that QT shortening is associated with ventricular fibrillation. Use caution when administering runfinamide with other drugs that cause a shortened QT interval as there may be a synergistic effect on the QT interval that would increase the QT shortening risk.
Abrupt discontinuation of rufinamide therapy should not be undertaken. If discontinuation becomes necessary, rufinamide should be withdrawn gradually (e.g., 25% every two days) to minimize the potential for seizure exacerbation or status epilepticus.
Rufinamide may cause drowsiness, dizziness, coordination abnormalities, gait disturbances, and ataxia. Patients should be advised to avoid driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether rufinamide adversely affects their cognitive and/or motor performance. Patients should also be informed of the possibility for enhanced drowsiness or dizziness with concurrent use of alcohol.
Limited data indicate that the pharmacokinetics of rufinamide are not affected by the presence of severe renal impairment (CrCl < 30 ml/min). However, hemodialysis reduces exposure of rufinamide by approximately 30%. This reduction should be considered when dosing rufinamide in patients receiving dialysis.
Rufinamide is not recommended in patients with severe hepatic impairment because the drug has not been studied in this patient population. Careful dose titration is advisable in patients with mild to moderate hepatic disease since rufinamide is extensively metabolized via the liver.
The number of geriatric adults enrolled in clinical trials of rufinamide was insufficient to determine if differences in response exist compared to younger adults. Because the older adult is more likely to have decreased renal, hepatic, or cardiac function, careful dosage titration is advised. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If rufinamide must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.
There are no adequate data on the developmental risks associated with rufinamide use during human pregnancy. In animal reproduction studies, oral administration of rufinamide resulted in developmental toxicity in pregnant rats and rabbits at clinically relevant doses. Decreased fetal weight and increased incidence of fetal skeletal abnormalities occurred with oral administration of rufinamide (0, 20, 100, or 300 mg/kg/day) to pregnant rats throughout organogenesis. 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 3,200 mg/day. Embryofetal death, decreased fetal body weight, and increased incidence of fetal visceral and skeletal abnormalities occurred with oral administration of rufinamide (0, 30, 200 and 1,000 mg/kg/day) to pregnant rabbits throughout organogenesis at doses of 200 and 1,000 mg/kg/day. The high dose (1,000 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. Decreased offspring growth and survival were observed at all rufinamide doses (0, 5, 30, or 150 mg/kg/day) given to rats throughout pregnancy and lactation. At the lowest dose (5 mg/kg/day), plasma exposure (AUC) was less than that in humans at the MRHD. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to rufinamide; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
Rufinamide should be avoided during breast-feeding. There are no data on the presence of rufinamide in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the risk and benefit of breast-feeding, taking into account the clinical need for rufinamide and the possibility of adverse effects on the breast-fed infant.
Rufinamide may be associated with reproductive risk. 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 infertility at all doses. 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.
For the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome:
Oral dosage:
Adults and Adolescents >= 17 years: Initially, 400-800 mg/day PO in 2 equally divided doses. Patients on valproate should begin rufinamide at a dose lower than 400 mg/day. The dosage should be increased every other day by 400-800 mg/day to a target and maximum dose of 3200 mg/day given in 2 equally divided doses. It is not known whether doses less than 3200 mg/day are effective. If drug discontinuation is necessary, rufinamide should be withdrawn gradually (e.g., 25% dose reduction every 2 days) to minimize the potential for increased seizure frequency.
Children and Adolescents 1-16 years: Initially, 10 mg/kg/day PO given as 2 equally divided doses. Pediatric patients receiving valproate should begin rufinamide at a dose lower than 10 mg/kg/day. The dose should be increased every other day by 10 mg/kg to a target dose of 45 mg/kg/day or 3200 mg/day, whichever is less, given in 2 equally divided doses. If drug discontinuation is necessary, rufinamide should be withdrawn gradually (e.g., 25% dose reduction every 2 days) to minimize the potential for increased seizure frequency.
Neonates and Infants: Safety and efficacy have not been established.
For the adjunctive treatment of refractory partial seizures*:
Oral dosage:
Adults: 3200 mg/day PO given in 2 divided doses was compared to placebo in a study of approximately 3 months duration (n=313). Subjects in the rufinamide group had a 20.4% decrease in median seizure frequency compared to baseline versus a 1.6% median increase in the placebo group. In a separate study (n=647), subjects were randomized to placebo or rufinamide (200 mg, 400 mg, 800 mg, or 1600 mg/day given in 2 divided doses). Subjects receiving rufinamide experienced a statistically significant reduction in the primary efficacy variable, seizure frequency per 28 days, compared to those receiving placebo. NOTE: For the treatment of seizures associated with Lennox-Gastaut syndrome, the manufacturer recommends dosage titration over several days to the target dose.
Maximum Dosage Limits:
-Adults
3200 mg/day PO.
-Geriatric
3200 mg/day PO.
-Adolescents
17 years: 3200 mg/day PO.
13-16 years: 45 mg/kg/day PO (Max: 3200 mg/day).
-Children
45 mg/kg/day PO (Max: 3200 mg/day).
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use in patients with severe hepatic impairment (Child-Pugh score 10-15) is not recommended. Exercise caution in patients with mild (Child-Pugh score 5-6) to moderate (Child-Pugh score 7-9) impairment. Rufinamide has not been studied in patients with hepatic impairment.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
Intermittent hemodialysis
Hemodialysis reduces exposure of rufinamide by approximately 30%. This reduction should be considered when dosing rufinamide in patients receiving dialysis.
*non-FDA-approved indication
Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with rufinamide may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with rufinamide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking rufinamide, reduce initial dosage and titrate to clinical response. If rufinamide is initiated a patient taking an opioid agonist, use a lower initial dose of rufinamide and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bortezomib: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as bortezomib, may occur during concurrent use with rufinamide.
Buprenorphine: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as buprenorphine, may occur during concurrent use with rufinamide.
Buprenorphine; Naloxone: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as buprenorphine, may occur during concurrent use with rufinamide.
Busulfan: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as busulfan, may occur during concurrent use with rufinamide.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and rufinamide. CNS depressants can potentiate the effects of cannabidiol.
Carbamazepine: (Moderate) Rufinamide is metabolized by carboxylesterases. The clearance of rufinamide may be increased due to induction of carboxylesterases by carbamazepine.
Cenobamate: (Moderate) Use caution when administering cenobamate and rufinamide due to the potential for a synergistic effect on the QT interval that would increase the QT shortening risk. Both cenobamate and rufinamide are associated with QT shortening. Nonclinical data indicate that QT shortening is associated with ventricular fibrillation.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Chlorzoxazone: (Moderate) In theory, plasma concentrations of chlorzoxazone or other CYP2E1 substrates may be increased due to the weak 2E1 inhibitory effects of rufinamide.
Cilostazol: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as cilostazol, may occur during concurrent use with rufinamide.
Cisapride: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as cisapride, may occur during concurrent use with rufinamide.
Clomipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Cyclosporine: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as cyclosporine, may occur during concurrent use with rufinamide.
Dapsone: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as dapsone, may occur during concurrent use with rufinamide.
Desipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Desogestrel; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as rufinamide, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dextromethorphan; Quinidine: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as quinidine, may occur during concurrent use with rufinamide.
Dienogest; Estradiol valerate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Docetaxel: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as docetaxel, may occur during concurrent use with rufinamide.
Donepezil: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as donepezil, may occur during concurrent use with rufinamide.
Donepezil; Memantine: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as donepezil, may occur during concurrent use with rufinamide.
Doxepin: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Drospirenone: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Drospirenone; Estetrol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Drospirenone; Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Estradiol; Levonorgestrel: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Estradiol; Norethindrone: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Estradiol; Norgestimate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethinyl Estradiol; Norelgestromin: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Ethinyl Estradiol; Norgestrel: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Ethosuximide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as ethosuximide, may occur during concurrent use with rufinamide.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Etonogestrel: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Etonogestrel; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Fosphenytoin: (Moderate) A population pharmacokinetic analysis showed an increase of 7 to 21% in phenytoin concentrations and a decrease of 25 to 46% in rufinamide concentrations during concurrent use. A similar interaction may be expected to occur with fosphenytoin.
Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as rufinamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Imipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Isavuconazonium: (Moderate) Use caution when administering rufinamide and isavuconazonium due to the potential for a synergistic effect on the QT interval that would increase the QT shortening risk. Both rufinamide and isavuconazonium are associated with QT shortening. Nonclinical data indicate that QT shortening is associated with ventricular fibrillation.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., rufinamide), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Shortening of the QT interval has occurred during treatment with rufinamide. Therefore, caution is advisable during co-administration with other drugs associated with QT-shortening including lamotrigine. In addition, a population pharmacokinetic analysis showed a 7% to 13% decrease in lamotrigine concentrations and no effect on rufinamide concentrations during concurrent use.
Leuprolide; Norethindrone: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Levonorgestrel: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Macimorelin: (Major) Discontinue rufinamide and allow a sufficient washout period to pass before administering macimorelin. Use of these drugs together can decrease macimorelin plasma concentrations, and may result in a false positive test for growth hormone deficiency. No drug-drug interaction studies have been conducted; however, macimorelin is primarily metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Midazolam: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as midazolam, may occur during concurrent use with rufinamide.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Nanoparticle Albumin-Bound Sirolimus: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as sirolimus, may occur during concurrent use with rufinamide.
Nefazodone: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as nefazodone, may occur during concurrent use with rufinamide.
Non-oral combination contraceptives: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norethindrone: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norgestimate; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Norgestrel: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Oral Contraceptives: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Paclitaxel: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as paclitaxel, may occur during concurrent use with rufinamide.
Paricalcitol: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as paricalcitol, may occur during concurrent use with rufinamide.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Phenobarbital: (Moderate) Rufinamide is metabolized by carboxylesterases. The clearance of rufinamide may be increased due to induction of carboxylesterases by phenobarbital.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Rufinamide is metabolized by carboxylesterases. The clearance of rufinamide may be increased due to induction of carboxylesterases by phenobarbital.
Phenytoin: (Moderate) A population pharmacokinetic analysis showed an increase of 7 to 21% in phenytoin concentrations and a decrease of 25 to 46% in rufinamide concentrations during concurrent use. A similar interaction may be expected to occur with fosphenytoin.
Primidone: (Moderate) A population pharmacokinetic analysis showed a decrease in rufinamide concentrations during concurrent use of primidone.
Protriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Quinidine: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as quinidine, may occur during concurrent use with rufinamide.
Quinine: (Minor) The potential interaction between quinine and rufinamide is unpredictable. CYP isozymes 3A4 and, to a lesser extent, 2E1 are involved in quinine metabolism. In theory, plasma concentrations of CYP2E1 substrates may be increased due to the weak 2E1 inhibitory effects of rufinamide. Conversely, the weak CYP3A4 inducer effects of rufinamide may result in decreased exposure of drugs that are metabolized by this isozyme.
Relugolix; Estradiol; Norethindrone acetate: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Segesterone Acetate; Ethinyl Estradiol: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer.
Sirolimus: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as sirolimus, may occur during concurrent use with rufinamide.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rufinamide. CNS depressants can potentiate the effects of stiripentol.
Tacrolimus: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as tacrolimus, may occur during concurrent use with rufinamide.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Trimipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Valproic Acid, Divalproex Sodium: (Major) A population pharmacokinetic analysis showed no effect on valproate concentrations and an increase of less than 16 to 70% in rufinamide concentrations during concurrent use. Adult patients currently stabilized on valproic acid or divalproex should initiate rufinamide therapy at a dosage lower than 400 mg/day, and pediatric patients stabilized on valproate therapy should begin rufinamide at a dose lower than 10 mg/kg/day. Similarly, patients stabilized on rufinamide before being prescribed valproate should initiate valproate therapy at a low dose followed by careful titration.
Zolpidem: (Minor) Rufinamide is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as zolpidem, may occur during concurrent use with rufinamide.
The exact mechanism by which rufinamide exerts its anticonvulsant effects is unknown. In vitro data suggest that the drug exerts its therapeutic effects through modulation of sodium channels, primarily through prolongation of the inactive state of the channel. Rufinamide slows sodium channel recovery from inactivation and limits sustained repetitive firing of sodium-dependent action potentials.
Rufinamide is administered orally. The volume of distribution is 50 liters at a dose of 3200 mg/day. Protein-binding is not considered to be clinically relevant (34%). Rufinamide is extensively metabolized in the liver, primarily to an inactive carboxylic acid metabolite produced via enzymatic hydrolysis. Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inhibitor of CYP2E1 and a weak inducer of CYP3A4. The elimination half-life is 6-10 hours. Less than 2% of a dose is excreted unchanged in the urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2E1, CYP3A4
Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inhibitor of CYP2E1 and a weak inducer of CYP3A4.
-Route-Specific Pharmacokinetics
Oral Route
The oral suspension is bioequivalent on a mg per mg basis to the tablet formulation. Following an oral dose, rufinamide tablets are well absorbed (>= 85%) under fed conditions; however, the rate of absorption is slow and the extent of absorption decreases with increasing doses. Food increases the extent of tablet absorption by 34% and peak exposure by 56%. Because clinical trials were conducted under fed conditions, administration with food is recommended. Maximum plasma concentrations occur 4-6 hours after administration under fed and fasted conditions.
-Special Populations
Renal Impairment
In patients with severe renal impairment (n = 9; CrCl < 30 mL/min), the pharmacokinetics of rufinamide were similar to that of healthy subjects during clinical trials. Patients undergoing hemodialysis 3 hours after rufinamide dosing showed a reduction in AUC and Cmax of 29% and 16%, respectively.
Pediatrics
Based on population analysis that included 85 pediatric patients, the pharmacokinetic profile of rufinamide in pediatric patients >= 1 year is similar to that of adults.
Geriatric
The elderly appear to demonstrate similar rufinamide pharmacokinetics as compared to adults.
Gender Differences
Differences in the pharmacokinetic parameters of rufinamide based upon gender do not appear to be clinically significant.
Ethnic Differences
No differences in clearance or volume of distribution have been observed between black and caucasian subjects. Information on other races is not available.