Abstract
Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs.
Highlights
Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to interactions
The purpose of the present review is to focus upon clinically relevant interactions between AEDs and AEDs in combination with other important therapeutic drug classes, with emphasis on pharmacokinetic interactions
Oxcarbazepine induces the metabolism of oral contraceprives (OCs), ethinyl estradiol and levonorgestrel, as their AUCs were reduced by 47 %, accompanied by a 45 % decrease in their half-lives, by concomitant administration of oxcarbazepine as studied in healthy women [83] (Level 1 interactions)
Summary
Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to interactions. All new AEDs are licensed for add-on therapy for epilepsy patients. Population-based studies of drug utilization demonstrate that 19-24 % of patients with epilepsy use polytherapy with AEDs [2,3,4]. In recent studies of children and adults with refractory epilepsy, 64 % used polytherapy with two or more AEDs, and 35 % of the adults suffered from CNS-related comorbid conditions, resulting in a considerable risk of interactions [5, 6]. Polytherapy and the potential for interactions with other drugs increase with increasing age, and the elderly is the largest group with newonset epilepsy having a considerable risk of interactions with commonly prescribed drugs [7]
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