ANTIEPILEPTIC DRUGS - A REVIEW OF CLINICALLY SIGNIFICANT DRUG-INTERACTIONS

Approximately 20 to 30% of patients with active intractable epilepsy a re commonly treated with polytherapy antiepileptic drug regimens, and these patients may experience complicated drug interactions. Furthermo re, because of the long term nature of treatment, the possibility of d rug interactions with drugs used for the treatment of concomitant dise ase is high. Classically, clinically significant drug interactions, bo th pharmacokinetic and pharmacodynamic, have been considered to be det rimental to the patient, necessitating dosage adjustment. However, thi s need not always be the case. With the introduction of new drugs (e.g . vigabatrin and lamotrigine) with known mechanisms of action, the pos sibility exists that these can be used synergistically. The most commo nly observed clinically significant pharmacokinetic interactions can b e attributed to interactions at the metabolic and serum protein bindin g levels. The best known examples relate to induction (e.g. phenobarbi tal, phenytoin, carbamazepine and primidone) or inhibition [e.g. valpr oic acid (sodium valproate)] of hepatic monooxygenase enzymes. The ext ent and direction of interactions between the different antiepileptic drugs are varied and unpredictable. Interactions in which the metaboli sm of phenobarbital, phenytoin or carbamazepine is inhibited are parti cularly important since these are commonly associated with toxicity. S ome inhibitory drugs include macrolide antibiotics, chloramphenicol, c imetidine, isoniazid and numerous sulphonamides. A reduction in effica cy of antibiotic, cardiovascular, corticosteroid, oral anticoagulant a nd oral contraceptive drugs occurs during combination therapy with enz yme-inducing antiepileptic drugs. Discontinuation of the enzyme induce r or inhibitor will influence the concentrations of the remaining drug (s) and may necessitate dosage readjustment.