Drug Interactions between Risperdal and valproic acid

MONITOR: Coadministration with risperidone may alter the serum concentrations of valproic acid, although data are conflicting. The mechanism is unknown but may be related to risperidone displacement of valproate from plasma proteins. In one pediatric patient, serum valproate level rose from 143 mg/L to 191 mg/L five days following the addition of risperidone, necessitating a 43% dosage reduction of valproic acid. The level declined to 108 mg/L within 3 days and stabilized thereafter. In another patient, the addition of risperidone was associated with a drop in serum valproate level. The combination has also been associated with the development of edema in one patient. In contrast, a group of investigators found no difference in the mean valproate serum concentration-to-dose ratio (C/D) in 4 patients treated concomitantly with risperidone compared to that of 172 patients who did not receive risperidone. In two of the four patients, serum valproate concentrations measured on occasions when they were not taking risperidone also indicate no change in valproate C/D. Another group of investigators compared trough serum valproate levels in 45 patients, 29 of whom received concurrent treatment with atypical antipsychotics, and found no significant difference among those receiving divalproex with risperidone versus those receiving divalproex alone or with olanzapine.

MANAGEMENT: Until further data are available, clinicians may consider monitoring the pharmacologic response and serum valproate levels more closely whenever risperidone is added to or withdrawn from therapy. Ambulatory patients should be made aware of the possibility of additive central nervous system effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

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