TROKENDI XR® EXTENDED-RELEASE CAPSULE 50MG

CAPSULE, EXTENDED RELEASE

**2 DOSAGE AND ADMINISTRATION** **2.1 Dosing in Monotherapy Epilepsy** When concomitant antiepileptic drugs (AEDs) are withdrawn to achieve monotherapy with topiramate, consideration should be given to the effects this may have on seizure control. Unless safety concerns require an abrupt withdrawal of the concomitant AED, a gradual discontinuation at the rate of approximately one-third of the concomitant AED dose every 2 weeks is recommended \[see _Warnings and Precautions (5.9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. When enzyme inducing drugs are withdrawn, topiramate levels will increase. A decrease in topiramate dosage may be required if clinically indicated. Adults Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased at 1- or 2-week intervals by increments of 25 or 50 mg/day, administered orally once daily. If the patient is unable to tolerate the titration regimen, smaller increments or longer intervals between increments can be used. Dose and titration rate should be guided by clinical outcome. The recommended initial target dose for topiramate monotherapy in adults is 100 mg/day and the maximum recommended daily dose is 500 mg. Some patients with refractory forms of epilepsy have tolerated topiramate monotherapy at doses of 1,000 mg/day. These dosing recommendations apply to all adults including the elderly in the absence of underlying renal disease. Pediatric Patients Ages 6 to 9 Years of Age Treatment of children aged 6 to 9 years should begin at 0.5 to 1 mg/kg nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 0.5 to 1 mg/kg/day, administered orally once daily. If the child is unable to tolerate the titration regimen, smaller increments or longer intervals between dose increments can be used. Dose and dose titration rate should be guided by clinical outcome. The recommended initial target dose range for topiramate monotherapy in children aged two years and above is 3 to 6 mg/kg/day. Children with recently diagnosed partial onset seizures have received doses of up to 500 mg/day. **2.2 Dosing in Adjunctive Therapy Epilepsy** Adults The recommended total daily dose of TROKENDI XR® as adjunctive therapy in adults should begin at 25 to 50 mg nightly for one week. Subsequently, at weekly or bi-weekly intervals, the dose should be increased by 25 to 50 mg/day and taken orally once daily. Dose titration should be guided by clinical outcome. Some patients may achieve efficacy with once-a-day dosing. In clinical trials as adjunctive therapy, 200 mg was effective and was the lowest dosage studied. This is therefore considered the minimum effective dose. The usual daily dose is 200 to 400 mg orally once daily. Individual patients have received doses as high as 1600 mg/day. These dosing recommendations apply to all adults, including the elderly, in the absence of underlying renal disease \[see _Warnings and Precautions (5.13)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. Pediatric Patients 6 to 16 Years of Age The recommended total daily dose of TROKENDI XR® as adjunctive therapy for patients 6 to 16 years of age with partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 mg/kg to 9 mg/kg orally once daily. Begin titration at 25 mg once daily (or less, based on a range of 1 mg/kg/day to 3 mg/kg/day) given nightly for the first week. Subsequently, increase the dosage at 1-or 2-week intervals by increments of 1 mg/kg/day to 3 mg/kg/day (administered orally once daily) to achieve optimal clinical response. Dose titration should be guided by clinical outcome. The total daily dose should not exceed 400 mg/day. Daily doses up to 30 mg/kg/day have been studied and were generally well tolerated. **2.3 Dosing in Migraine Prophylaxis** Adults The recommended total daily dose of TROKENDI XR® as treatment for prophylaxis of migraine headache in adult patients is 100 mg once daily. Some patients may experience a benefit at a total daily dose of 50 mg/day. Patients have received a total daily dose up to 200 mg/day. Dose and titration rate should be guided by clinical outcome. Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased in increments of 25 mg/day administered at 1-week intervals. If the patient is unable to tolerate the titration regimen, longer intervals between dose adjustments can be used. **2.4 Administration with Alcohol** Alcohol use should be completely avoided within 6 hours prior to and 6 hours after TROKENDI XR® administration \[see _Warnings and Precautions (5.5)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. **2.5 Dose Modifications in Patients with Renal Impairment** In patients with renal impairment (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose of TROKENDI XR® is recommended \[see _Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. **2.6 Dosage Modifications in Patients Undergoing Hemodialysis** To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of TROKENDI XR® may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed _\[see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. **2.7 Administration Instructions** TROKENDI XR® can be taken without regard to meals. Swallow capsule whole and intact. Do not sprinkle on food, chew, or crush.