No

Anticonvulsant, Miscellaneous

Adjunctive therapy for partial onset seizures in adults and pediatric patients (ages 2-16 years)

Orphan drug: Topiramate has also been granted orphan drug status for the treatment of Lennox-Gastaut syndrome

C

Breast-feeding/lactation: In studies of rats topiramate has been shown to be secreted in milk; however, it has not been studied in humans

Hypersensitivity to topiramate or any component

Avoid abrupt withdrawal of topiramate therapy, it should be withdrawn slowly to minimize the potential of increased seizure frequency. The risk of kidney stones is about 2-4 times that of the untreated population, the risk of this event may be reduced by increasing fluid intake. Use cautiously in patients with hepatic or renal impairment, during pregnancy, or in nursing mothers. May cause paresthesias. Sedation, psychomotor slowing, confusion, and mood disturbances may occur with topiramate use. Patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated.

>10%:

Central nervous system: Dizziness, ataxia, somnolence, psychomotor slowing, nervousness, memory difficulties, speech problems

Gastrointestinal: Nausea

Neuromuscular & skeletal: Paresthesia, tremor

Ocular: Nystagmus, diplopia, abnormal vision

Respiratory: Upper respiratory infections

1% to 10%:

Cardiovascular: Chest pain, edema

Central nervous system: Language problems, abnormal coordination, confusion, depression, difficulty concentrating, hypoesthesia

Endocrine & metabolic: Hot flashes

Gastrointestinal: Dyspepsia, abdominal pain, anorexia, constipation, xerostomia, gingivitis, weight loss

Neuromuscular & skeletal: Myalgia, weakness, back pain, leg pain, rigors

Otic: Decreased hearing

Renal: Nephrolithiasis

Respiratory: Pharyngitis, sinusitis, epistaxis

Miscellaneous: Flu-like symptoms

Activated charcoal has not been shown to adsorb topiramate and is, therefore, not recommended; hemodialysis can remove drug, however, most cases do not require removal and instead is best treated with supportive measures

CYP2C19 enzyme substrate; CYP2C19 enzyme inhibitor

Digoxin levels and ethinyl estradiol blood levels are decreased when coadministered with topiramate

Concomitant administration with other CNS depressants will increase its sedative effects; coadministration with other carbonic anhydrase inhibitors may increase the chance of nephrolithiasis

Topiramate may increase phenytoin concentration by 25%

Topiramate may decrease valproic acid concentration by 11%

Mechanism is not fully understood, it is thought to decrease seizure frequency by blocking sodium channels in neurons, enhancing GABA activity and by blocking glutamate activity

Absorption: Good; unaffected by food

Protein binding: 13% to 17%

Metabolism: Minimal, primarily eliminated unchanged in urine (~70% of administered dose)

Bioavailability: 80%

Half-life: Mean: 21 hours in adults

Time to peak serum concentration: ~2-4 hours

Elimination: Primarily eliminated unchanged in the urine

Dialyzable: ~30%

Adults: Initial: 25-50 mg/day; titrate in increments of 25-50 mg per week until an effective daily dose is reached; the daily dose may be increased by 25 mg at weekly intervals for the first 4 weeks; thereafter, the daily dose may be increased by 25-50 mg weekly to an effective daily dose (usually at least 400 mg); usual maximum dose: 1600 mg/day

Note: A more rapid titration schedule has been previously recommended (ie, 50 mg/week), and may be attempted in some clinical situations; however, this may reduce the patient's ability to tolerate topiramate.

Children 2-16 years: Partial seizures (adjunctive therapy): Initial dose titration should begin at 25 mg (or less, based on a range of 1-3 mg/kg/day) nightly for the first week. Dosage may be increased in increments of 1-3 mg/kg/day (administered in two divided doses) at 1- or 2-week intervals to a total daily dose of 5-9 mg/kg/day.

Dosing adjustment in renal impairment: Cl_cr <70 mL/minute: Administer 50% dose and titrate more slowly

Dosing adjustment in hepatic impairment: Clearance may be minimally reduced

Oral: May be administered without regard to meals

No information available to require special precautions

Up to 10% of patients may experience gingivitis and dry mouth

Take exactly as directed; do not increase dose or frequency or discontinue without consulting prescriber. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, dizziness, disturbed concentration, memory changes, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); mouth sores, nausea, vomiting, or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Wear identification of epileptic status and medications. Report behavioral or CNS changes; skin rash; muscle cramping, weakness, tremors, changes in gait; chest pain, irregular heartbeat, or palpitations; hearing loss; cough or difficulty breathing; worsening of seizure activity, or loss of seizure control. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant or intend to be pregnant. Consult prescriber if breast-feeding.

Capsule (Topamax® Sprinkles): 15 mg, 25 mg

Tablet: 25 mg, 100 mg, 200 mg

Doose DR, Walker SA, Gisclon LG, et al, "Single-Dose Pharmacokinetics and Effect of Food on the Bioavailability of Topiramate, a Novel Antiepileptic Drug," J Clin Pharmacol, 1996, 36(10):884-91.

Glauser TA, "Topiramate Use in Pediatric Patients," Can J Neurol Sci, 1998, 25(3):S8-12.

Glauser TA, Clark PO, and Strawsburg R, "A Pilot Study of Topiramate in the Treatment of Infantile Spasms," Epilepsia, 1998, 39(12):1324-8.

Glauser TA, "Preliminary Observations on Topiramate in Pediatric Epilepsies," Epilepsia, 1997, 38(Suppl 1):S37-41.

Sachdeo RC, "Topiramate. Clinical Profile in Epilepsy," Clin Pharmacokinet, 1998, 34(5):335-46.