Treatment of concomitant illnesses in patients receiving anticonvulsants: drug interactions of clinical significance

Abstract

As epilepsy often is a chronic condition requiring prolonged therapy with anticonvulsants, patients being treated for epilepsy can be at risk when they are prescribed other drugs for concomitant diseases. Pharmacokinetic interactions can occur at each step of drug disposition (absorption, distribution, metabolism and elimination). Although such interactions may occur frequently with some drugs, only some will be clinically relevant. Alterations in the hepatic biotransformation of metabolised drugs due to hepatic isoenzyme induction or inhibition is of particular concern. The consequences of pharmacokinetic interactions are either accumulation of the drug leading to toxicity, or lowering of plasma concentrations resulting in reduced efficacy. Clinically relevant interactions depend on the structure, dosage and duration of administration of interacting agents, and on the individual's genetic make-up. In the past, drug interactions have been analysed empirically. At present, at least for interactions between drugs that are biotransformed in the liver, the risk should be predicted by considering the individual cytochrome P450 isoforms involved in the metabolism of coadministered drugs. Although drug-drug interactions can be predicted, their extent cannot be due to large interindividual variability. Even if nearly all drug combinations could be used with close clinical surveillance and blood concentration determinations, drugs that are not metabolised and are not highly protein bound, as are several of the new anticonvulsants, such as gabapentin, lamotrigine and vigabatrin, have a clear advantage in terms of a lower interaction potential.