rufinamide

Rufinamide oral suspension should be given with food. ( 2.2 ) 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 mg to 800 mg per day in two equally divided doses ( 2.1 ) Increase by 400 mg to 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 oral suspension 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 oral suspension in adults with Lennox-Gastaut Syndrome is 400 mg to 800 mg per day administered in two equally divided doses. The dose should be increased by 400 mg to 800 mg…

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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 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:…

Rufinamide oral suspension is contraindicated in patients with Familial Short QT syndrome [see Warnings and Precautions (5.3) ] . Rufinamide oral suspension is contraindicated in patients with Familial Short QT syndrome ( 4 )

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.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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 mcg/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)].