Topirva XR 100

Epilepsy, Migraine prophylaxis, Seizures associated w/ Lennox-gastaut syndrome

May be taken with or without food.

Oral Partial-Onset or Primary Generalized Tonic-Clonic Seizures Monotherapy Adult: 25 mg PO q12hr initially; may increase by 50 mg/day at weekly intervals to 200 mg PO q12hr. Adjunctive therapy 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr. Lennox-Gastaut Syndrome Indicated as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr Migraine Headache Indicated for prophylaxis of migraine headache Titrate over 4 wk to achieve a dose of 50 mg PO BID Week 1: 25 mg PO at night Week 2: 25 mg PO BID Week 3: 25 mg PO in the morning and 50 mg at night Week 4: 50 mg PO BID Hepatic impairment: Dosage adjustment may be needed.

Oral Partial-Onset or Primary Generalized Tonic-Clonic Seizures Monotherapy <2 years: Safety and efficacy not established 2 to <10 years: 25 mg PO at night for 1 week; titrate dose over 5-7 weeks to target daily maintenance dose (weight based) and divide into q12hr dosing schedule Weight-based dosing Up to 11 kg: 150 mg/day minimum; 250 mg/day maximum 12-22 kg: 200 mg/day minimum; 300 mg/day maximum 23-31 kg: 200 mg/day minimum; 350 mg/day maximum 32-38 kg: 250 mg/day minimum; 350 mg/day maximum >38 kg: 250 mg/day minimum; 400 mg/day maximum >10 years 25 mg PO q12hr initially Titrate by increments of 50 mg/week up to 200 mg q12hr Adjunctive therapy <2 years: Safety and efficacy not established 2-16 years: 25 mg PO qHS(once at night) initially for first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day PO divided q12hr at 1-2 week intervals to 5-9 mg/kg/day divided q12hr >17 years: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr for generalized tonic/clonic seizures Lennox-Gastaut Syndrome Adjunctive therapy <2 years: Safety and efficacy not established 2-16 years: 25 mg PO qHS initially for first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day PO divided q12hr at 1-2 week intervals to 5-9 mg/kg/day divided q12hr >17 years: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr for generalized tonic/clonic seizures Migraine Headache Indicated for prophylaxis of migraine headache <12 years: Safety and efficacy not established Guide dose/titration rate by clinical outcome; if needed, use longer intervals between dose adjustments >12 years Titrate over 4 wk to achieve a dose of 50 mg PO BID Week 1: 25 mg PO qHS(once at night) Week 2: 25 mg PO BID Week 3: 25 mg PO in the morning and 50 mg HS Week 4: 50 mg PO BID

Renal impairment: Moderate to severe: Doses should be halved. Haemodialysis: supplemental dose equal to about ½ of the daily dose should be given in divided doses (at the start and finish of haemodialysis).

Contraindicated in persons showing hypersensitivity to any component of this preparation.

Topiramate is a sulfamate-substituted monosaccharide with precise mechanism of action unknown. It may be due to various mechanisms e.g. blocking of voltage-dependent sodium channels; augmenting the activity of ?-aminobutyric acid (GABA) at GABA-A receptor; antagonising AMPA/kainate glutamate receptors; inhibiting carbonic anhydrase.

Renal or hepatic impairment, pregnancy, lactation. May impair ability to drive or operate machinery. Maintain adequate hydration to reduce the risk of renal calculi especially in predisposed patients. Measure serum bicarbonate at baseline and periodically during treatment. Avoid abrupt withdrawal; decrease dose by 100 mg daily at wkly intervals. Seek immediate medical attention if blurred vision or eye pain. Monitor closely for decreased sweating and increased body temperature, especially in hot weather. Ensure proper hydration before and during activities or exposure to warm temperatures. Lactation: Excreted in milk; use caution

>10% Decrease in serum bicarbonate (7-67%),Dizziness (4-29%),Fatigue (9-16%),Ataxia (6-16%),Nervousness (9-18%),Paresthesia (1-11%),Psychomotor slowing (3-13%),Abnormal vision (2-13%),Anorexia (4-24%),Confusion (4-11%),Decreased memory (2-12%),Nausea (6-10%),Speech disorder (2-13%),Injury (14%) 1-10% Abdominal pain (6-10%),Weight loss (4-9%),Diplopia (1-10%),Mood problems (<6%),Pharyngitis (6%),Tremor (3-9%),Abnormal gait (3-8%),Apathy (1%),Asthenia (1-5%),Dry mouth (2%),Menorrhagia (1-2%),Skin disorder (2-3%),Taste change (2%),Edema (2%),Hypertension (1-2%),Syncope (1%),Bradycardia (1%),Pallor (1%) <1% Angina,Erythema,Hepatic failure,Hyperthermia,Hypokalemia,Neuropathy,Toxic epidermal necrolysis

Coadmin with antiepileptic drugs e.g. phenytoin, carbamazepine, phenobarbital decreases plasma concentration of topiramate. Possible increase in phenytoin levels. Increased risk of renal stone formation with carbonic anhydrase inhibitors e.g. acetazolamide. Increased risk of CNS depression with CNS depressants and alcohol. Increased risk of hyperammonaemia and encephalopathy with valproic acid. Increased risk of contraceptive failure in women taking combined oral contraceptives.