Topiramate (Topamax, Ortho-McNeil)
Topiramate was just released in 1997. It is a sulfa- related drug, like acetazolamide (Diamox) and zonisamide. As such, it produces occasional allergic reactions, and may precipitate kidney stones. Topiramate is a substantially effective medication, with responder rates in the 50% range in intractable epilepsy. It also has the advantage of being a broad-spectrum antiepileptic medication, in a category with valproic acid, lamotrigine, zonisamide, and benzodiazepines.
Topiramate is given in a twice-daily dosing regimen, typically in doses of 200 - 400 mg total per day. However, this typical dose may in fact be too high, and evidence is accumulating that doses in the 100 - 200 mg per day range may be effective without as many side effects. The usual side effects include dizziness, sleepiness and unsteadiness.
In addition, the medication produces temporary impairment of thinking and memory in about 30% of cases of people taking full doses. Subtle impairments, such as slow thinking and slow talking, noticed mainly by family may occur in even more. Cognitive problems are more common in people taking doses of topiramate higher than 400 mg per day, during initiation of the drug, and in people on topiramate in combination with other AEDs (polypharmacy).
Dr. Fisher says he uses topiramate when he wants a powerful, broad-spectrum AED, but its use is limited by a relatively high incidence of thinking problems, a risk for kidney stones, and the need to start the drug slowly. Because of kidney stone risk, topiramate theoretically probably should not be used in conjunction with zonisamide (Zonegran) or acetazolamide (Diamox), although no actual proof exists for high kidney stone risk with such combination therapy. Some people like the common weight loss side effect of topiramate; others find it to be a problem.
Summary Data for Topiramate
Pill sizes: 15, 25 mg sprinkle capsule;
25 mg (round white tablet, not scored)
100 mg (round peach tablet, not scored)
200 mg (round salmon tablet, not scored)
Liquid for oral: none.
Injectable: none.
Typical adult starting dose: 25-50 mg in 1-2 divided doses.
Typical adult dose: 400 - 600 mg per day in 2 divided doses. Some do better on as little as 100 - 200 mg/d. Patients usually start with 25 mg per week, and increase by 25 mg daily each week to 200 mg in a twice-daily dose. Physicians can then switch patients to 100 mg pills and move to 100, 200 mg per day for a week, then 200, 200 mg (400 mg/d) as a target dose.
Typical pediatric dose: Start 1 - 3 mg/kg/d, then increase over a month or two to 5 - 9 mg/kg/d.
Metabolism: 70% unchanged in the kidney when the only drug, but more complex with polypharmacy.
Half-life: 12 - 30 hours, longer with kidney failure.
Serum levels: not established
Pregnancy: Category C - can cause birth defects in animals, unknown in humans.
Drugs that lower TPM levels: Dilantin, Tegretol, phenoarbital
TPM increases effects of: Dilantin, Diamox (more kidney stone risk), Zonegran (more kidney stone risk).
TPM decreases effects of other drugs: Oral contraceptives.
Dangerous Side Effects
Severe thinking impairment, kidney stones (2 - 3%), behavior problems, precipitation of acute glaucoma.
Common Side Effects
Thinking impairment, GI upset, dizziness, sleepiness, unsteadiness, weight loss.
Other Side Effects
Dizziness, numbness.