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Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs.
Clin Pharmacokinet 2013; 52(11):927-66CP

Abstract

Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide; 16 in total. Because often the treatment of epilepsy is lifelong, and because patients are commonly prescribed polytherapy with other AEDs, AED interactions are an important consideration in the treatment of epilepsy and indeed can be a major therapeutic challenge. For new AEDs, their propensity to interact is particularly important because inevitably they can only be prescribed, at least in the first instance, as adjunctive polytherapy. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. The principal pharmacokinetic interaction relates to hepatic enzyme induction or inhibition whilst pharmacodynamic interactions principally entail adverse effect synergism, although examples of anticonvulsant synergism also exist. Overall, the new AEDs are less interacting primarily because many are renally excreted or not hepatically metabolised (e.g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin) and most do not (or minimally) induce or inhibit hepatic metabolism. A total of 139 pharmacokinetic interactions between concurrent AEDs have been described. The least pharmacokinetic interactions (n ≤ 5) are associated with gabapentin, lacosamide, tiagabine, vigabatrin and zonisamide, whilst lamotrigine (n = 17), felbamate (n = 15), oxcarbazepine (n = 14) and rufinamide (n = 13) are associated with the most. To date, felbamate, gabapentin, oxcarbazepine, perampanel, pregabalin, retigabine, rufinamide, stiripentol and zonisamide have not been associated with any pharmacodynamic interactions.

Authors+Show Affiliations

Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK, p.patsalos@ucl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23784470

Citation

Patsalos, Philip N.. "Drug Interactions With the Newer Antiepileptic Drugs (AEDs)--part 1: Pharmacokinetic and Pharmacodynamic Interactions Between AEDs." Clinical Pharmacokinetics, vol. 52, no. 11, 2013, pp. 927-66.
Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52(11):927-66.
Patsalos, P. N. (2013). Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clinical Pharmacokinetics, 52(11), pp. 927-66. doi:10.1007/s40262-013-0087-0.
Patsalos PN. Drug Interactions With the Newer Antiepileptic Drugs (AEDs)--part 1: Pharmacokinetic and Pharmacodynamic Interactions Between AEDs. Clin Pharmacokinet. 2013;52(11):927-66. PubMed PMID: 23784470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. A1 - Patsalos,Philip N, PY - 2013/6/21/entrez PY - 2013/6/21/pubmed PY - 2014/6/11/medline SP - 927 EP - 66 JF - Clinical pharmacokinetics JO - Clin Pharmacokinet VL - 52 IS - 11 N2 - Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide; 16 in total. Because often the treatment of epilepsy is lifelong, and because patients are commonly prescribed polytherapy with other AEDs, AED interactions are an important consideration in the treatment of epilepsy and indeed can be a major therapeutic challenge. For new AEDs, their propensity to interact is particularly important because inevitably they can only be prescribed, at least in the first instance, as adjunctive polytherapy. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. The principal pharmacokinetic interaction relates to hepatic enzyme induction or inhibition whilst pharmacodynamic interactions principally entail adverse effect synergism, although examples of anticonvulsant synergism also exist. Overall, the new AEDs are less interacting primarily because many are renally excreted or not hepatically metabolised (e.g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin) and most do not (or minimally) induce or inhibit hepatic metabolism. A total of 139 pharmacokinetic interactions between concurrent AEDs have been described. The least pharmacokinetic interactions (n ≤ 5) are associated with gabapentin, lacosamide, tiagabine, vigabatrin and zonisamide, whilst lamotrigine (n = 17), felbamate (n = 15), oxcarbazepine (n = 14) and rufinamide (n = 13) are associated with the most. To date, felbamate, gabapentin, oxcarbazepine, perampanel, pregabalin, retigabine, rufinamide, stiripentol and zonisamide have not been associated with any pharmacodynamic interactions. SN - 1179-1926 UR - https://www.unboundmedicine.com/medline/citation/23784470/Drug_interactions_with_the_newer_antiepileptic_drugs__AEDs___part_1:_pharmacokinetic_and_pharmacodynamic_interactions_between_AEDs_ L2 - https://dx.doi.org/10.1007/s40262-013-0087-0 DB - PRIME DP - Unbound Medicine ER -