Drug Interactions

The goal of treatment is to control seizures using a single agent maintained at serum concentrations that do not produce adverse effects. If seizures persist, the dosage should be gradually increased until seizure control is achieved or intolerable side effects appear. Trough blood levels should be obtained during steady-state conditions, generally no sooner than five half-lives after a dosage adjustment. A second agent is introduced only after an adequate trial of the first drug has failed. If polytherapy is required, drugs should be chosen with different mechanisms of action and side effect profiles to maximize anticonvulsant benefit and minimize toxicity. Interactions among the various AEDs must also be kept in mind in the selection of drug combinations ( Table 52:7 ). Patients whose seizures continue despite adequate trials of several AEDs should be referred to an epilepsy center for further evaluation.

Clinical and laboratory monitoring is routinely performed in patients taking anticonvulsant medication. Blood levels help to achieve maximal medication effect and identify patients who are noncompliant. The older agents have an established therapeutic range within which most patients experience an improvement in seizure control and few or no adverse reactions. The therapeutic range should serve as a general guide only. Some patients become seizure-free with subtherapeutic serum concentrations, whereas others require levels in the "toxic" range to achieve satisfactory seizure control.

No standard recommendations exist for the timing of laboratory monitoring. Hematological parameters should be assessed periodically during carbamazepine, ethosuximide, and valproic acid therapy. Hepatic transaminases should be monitored in patients taking carbamazepine, valproic acid, phenytoin, primidone, and phenobarbital. Laboratory monitoring is particularly important in the setting of hepatic or renal dysfunction and during pregnancy. Free levels are useful when protein binding is altered such as in pregnancy, uremia, and hypoalbuminemia, and with highly protein-bound drugs like phenytoin and valproic acid.

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