Summary of Product Characteristics 1. Name of The
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SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Topiramat Orion 25 mg film-coated tablets Topiramat Orion 50 mg film-coated tablets Topiramat Orion 100 mg film-coated tablets Topiramat Orion 200 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Topiramat Orion 25 mg film-coated tablets: Each film-coated tablet contains 25 mg topiramate. Excipient: 20.09 mg lactose/film-coated tablet Topiramat Orion 50 mg film-coated tablets: Each film-coated tablet contains 50 mg topiramate. Excipient:. 40.19 mg lactose/film-coated tablet Topiramat Orion 100 mg film-coated tablets: Each film-coated tablet contains 100 mg topiramate. Excipient: 80.37 mg lactose/film-coated tablet Topiramat Orion 200 mg film-coated tablets: Each film-coated tablet contains 200 mg topiramate. Excipient: 58.62 mg lactose/film-coated tablet For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Topiramat Orion 25 mg film-coated tablets: White, circular, biconvex film-coated tablets debossed with ‘E’ on one side and ‘22’ on the other side. Topiramat Orion 50 mg film-coated tablets: Light yellow colored, circular, biconvex film-coated tablets debossed with ‘E’ on one side and ‘33’ on the other side. Topiramat Orion 100 mg film-coated tablets: Dark yellow colored, circular, biconvex beveled edged film-coated tablets debossed with ‘E’ on one side and ‘23’ on the other side. Topiramat Orion 200 mg film-coated tablets: Pink colored, circular, biconvex, beveled edged film-coated tablets debossed with ‘E’ on one side and ‘24’ on the other side. 1 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Epilepsy - as monotherapy in adults, adolescents and children with 2 years and above who have generalised tonic- clonic seizures and/or partial onset seizures (with or without secondarily generalised seizures) - as adjunctive therapy in adults, adolescents and children with 2 years and above who have partial seizures (with or without secondarily generalised seizures) and/or primary generalised tonic-clonic seizures and/or seizures associated with Lennox Gastaut Syndrome. Migraine In adults: The prophylaxis of migraine headache in patients intolerant of or unresponsive to other migraine treatments. Topiramate is not intended to treat an acute migraine attack. 4.2 Posology and method of administration General: For optimal seizure control and to avoid dose-dependent undesirable effects it is recommended that therapy be initiated at a low dose followed by titration to a clinically effective dose. Estimation of plasma levels is not necessary for optimisation of topiramate therapy. Topiramat Orion should not be divided or broken. Topiramat Orion can be taken without regard to meals and should be swallowed unchewed with a sufficient quantity of liquid. When concomitant antiepilepsy drugs (AED) 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. When enzyme inducing medicinal products are withdrawn topiramate levels will increase. A decrease in topiramate dosage may be required if clinically indicated. Topiramate should be withdrawn gradually to minimise the potential of increased seizure frequency. In clinical trials, dosages were decreased by 50–100 mg/day at weekly intervals. In some patients, dose decrease was accelerated without complications. The following dosing recommendations apply to children, adolescents and all adults, including the elderly, in the absence of underlying renal disease (see section 4.4). For doses not realisable/practicable with this medicinal product other strengths of this medicinal product are available. Monotherapy in Adults and Adolescents aged 12 years and over: Titration should begin at 25 mg in the evening for 7 days. The dosage should then be increased at 7 day or 14 day intervals by increments of 25–50 mg/day, administered in two divided doses. If the patient is unable to tolerate the titration regimen, smaller dose increments or longer intervals between dose increments may be used. Dose titration should be guided by clinical outcome. The recommended initial target dose for topiramate monotherapy in adults is 100 mg/day. The recommended maximum daily dose is 400 mg. Children of 2 years and above 2 Treatment should begin at 0.5–1 mg/kg in the evening for the first week. The dosage should then be increased at 7 day or 14 day intervals by increments of 0.5–1 mg/kg/day, administered in two divided doses. 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 is 3–6 mg/kg/day. Children less than 2 years The use of the medicinal product in children less than 2 years of age is not recommended as no data are available. Adjunctive Therapy in Adults and Adolescents aged 12 years and over: Titration should begin at 25–50 mg in the evening for 7 days. The dosage should then be increased at 7 day or 14 day intervals by increments of 25–50 mg/day, administered in two divided doses. If the patient is unable to tolerate the titration regimen, smaller dose increments or longer intervals between dose increments may be used. Dose titration should be guided by clinical outcome. The minimal effective dose given in clinical studies as adjunctive therapy was 200 mg per day. The usual total daily dose is 200 mg to 400 mg administered in two divided doses. Some patients may achieve efficacy with a once-a-day dosing. Some patients may require higher doses. Some patients may require the maximum daily dose of 800 mg. Children of 2 years and above The recommended total daily dose of topiramate is approximately 5–9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day in the evening for the first week (or lower, e.g. 0.5–1 mg/kg/day). The dosage should then be increased at 7 day or 14 day intervals by increments of about 1 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome. In individual children daily doses up to 30 mg/kg/day have been studied and were generally well tolerated. Prophylaxis of Migraine in Adults: Titration should begin at 25 mg in the evening for 7 days. The dosage should then be increased at 7 day intervals by increments of 25 mg/day. If the patient is unable to tolerate the regimen, longer intervals between dose adjustments may be used. The recommended total daily dose of topiramate for prophylaxis of migraine in adults is 100 mg/day administered in two divided doses. Higher doses do not result in increased benefit. Some patients may experience a benefit at a total daily dose of 50 mg/day. Dose and titration should be guided by clinical outcome. Impaired RenalFunction: For patients with moderate (creatinine clearance 30-69 ml/min) and severe (creatinine clearance <30 ml/min) renal dysfunction, it is recommended to start with half of the daily dose than usual and to titrate with smaller steps and at slower pace as is usual. As with all patients, the titrations schedule should be guided by clinical outcome with the knowledge that it may require longer to reach steady-state after each dose change in renally impaired patients. In patients with moderate or severe renal impairment, it may take 10 to 15 days to reach steady concentrations as compared to 4 to 8 days in patients with normal renal function. Impaired HepaticFunction: In hepatically impaired patients, topiramate should be administered with caution as the clearance of topiramate may be decreased (see section 4.4 and 5.2). 3 Patients Undergoing Haemodialysis: Topiramate is removed from plasma by haemodialysis. Therefore a supplemental dose of topiramate equal to approximately one-half the daily dose should be administered on haemodialysis days. The supplemental dose should be administered in divided doses at the beginning and completion of the haemodialysis procedure. The supplemental dose may differ based on the characteristics of the dialysis equipment being used. As for all patients, the dose titration should be guided by clinical outcome (e.g. seizure control, avoidance of side effects). 4.3 Contraindications Hypersensitivity to topiramate or to any of the excipients in the medicinal product. Treatment for prophylaxis of migraine during pregnancy, and in women of child bearing potential if not using an effective method of contraception (see section 4.6). 4.4 Special warnings and precautions for use General: Hydration: Adequate hydration while using topiramate is important. Hydration can reduce the risk of nephrolithiasis (see below). Treatment with topiramate may decrease sweating, primarily in paediatric patients. Activities such as exercise or exposure to warm temperatures while using topiramate may increase the risk of heat-related adverse events (see section 4.8). Weight loss: Patients on long-term topiramate treatment should be regularly monitored for weight loss. A dietary supplement or increased food intake may be considered if the patient is losing weight or has inadequate weight gain while on this medication. If clinically significant weight loss occurs, discontinuation of the medication should be considered. Topiramate should only be used for the prophylaxis of migraine and is not intended for acute treatment. Renal Impairment: Caution should be exercised when treating patients with moderate to severe renal impairment (see section 4.2) as subjects with known renal impairment may require longer to reach a steady state at each dose.