Interactions of antiepileptic drugs

Several interactions involving antiepileptic drugs are based on changes in the rate of their metabolism and elimination, with concomitant rise or fall of plasma levels. Thus, phenobarbital generally induces the production of the DPH metabolizing enzyme, but its presence inhibits the action of that enzyme. The net result depends upon the balance between these factors in individual patients. Either a decline, a rise, or no change of the DPH plasma level may occur after the onset of administration of phenobarbital. Drugs that may cause elevation of the DPH plasma level include disulfiram, sulthiame, bishydroxycoumarin, chloramphenicol, phenyramidol, benzodiazepines, sulfamethizole, and isoniazid. Isoniazid has been shown experimentally to be a strong inhibitor of DPH metabolism. The extent of DPH plasma level elevation by INH is related to the genetic make-up of individual patients. The highest and frequently toxic DPH plasma levels were seen in very slow INH inactivators. The incidence of clinically significant interactions is not high with most drug combinations; marked changes of antiepileptic drug levels occur only in apparently susceptible individuals. The effects of interactions are not necessarily detrimental; elevation of a low ineffective level may improve seizure control. A rise to a toxic level range requires reduction of the dose of primary drug or elimination of interfering drugs. Monitoring the blood levels of anti-epileptic drugs provides the best means to anticipate interactions and to regulate the doses when multiple medications have to be used.