Abstracts

To determine clinical correlations of dosage and serum concentrations of topiramate (TPM) during clinical practice at a comprehensive epilepsy center. We reviewed 1237 drug regimens and 469 serum levels from 342 patients who received topiramate. Data collected included concomitant antiepileptic drugs (AEDs), doses, clinical toxicity and specific side effects. [lsquo]Toxic[rsquo] was defined as causing side effects that led to a dosage change or discontinuation of TPM. Rates of toxicity and specific side effects were calculated and analyzed for correlation with dosage and serum concentration. Correlation was tested using binary logistic regression, with significance set at p[lt]0.05. Overall, 163/1237 (13.2%) regimens included side effects requiring TPM dosage or medication change and 73/1237 (5.9%) regimens included side effects requiring TPM discontinuation. 129/342 (37.7%) patients had at least one toxic regimen and 70/342 (20.5%) patients had side effects that led to TPM discontinuation. Toxicity correlated with dosage (p[lt]0.01) but not serum concentrations. The mean TPM dosage was 222 mg/day and the mean serum concentration was 7.2 [mu]g/ml. Cognitive side effects and drowsiness were the most common side effects and led to a dosage or medication change in 14.9% and 7.3% of patients, respectively. Both cognitive side effects and drowsiness correlated with dosage (p[lt]0.05). At dosages [le]200 mg/day, 26/222 (11.7%) patients experienced cognitive side effects that led to a dosage or medication change. At dosages [underline][gt] [/underline]400 mg/day, 20/69 (29.0%) patients experienced cognitive side effects that led to a dosage or medication change. 3/342 (0.9%) patients experienced renal stones due to TPM. No patients experienced glaucoma. TPM is well tolerated, with approximately 80% of patients never experiencing side effects leading to discontinuation. Tolerability of TPM is correlated with dosage but not serum concentration. The most common side effects are cognitive side effects and drowsiness, both of which are correlated with dosage. (Supported by Elan, Glaxo, Ortho-McNeil, Pfizer, and UCB Pharma.)