Tags

Type your tag names separated by a space and hit enter

Drug interactions involving the new second- and third-generation antiepileptic drugs.
Expert Rev Neurother 2010; 10(1):119-40ER

Abstract

During the period 1989-2009, 14 new antiepileptic drugs (AEDs) were licensed for clinical use and these can be subdivided into new second- and third-generation AEDs. The second-generation AEDs comprise felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. The third-generation AEDs comprise eslicarbazepine acetate and lacosamide. The interaction propensity of AEDs is very important because all new AEDs are licensed, at least in the first instance, as adjunctive therapy. The present review summarizes the interactions (pharmacokinetic and pharmacodynamic) that have been reported with the newer AEDs. The pharmacokinetic interactions include those relating to protein-binding displacement from albumin in blood, and metabolic inhibitory and induction interactions occurring in the liver. Overall, the newer AEDs are less interacting because their pharmacokinetics are more favorable and many are minimally or not bound to blood albumin (e.g., eslicarbazepine, felbamate, gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) and are primarily renally excreted or metabolized by noncytochrome P450 or uridine glucoronyl transferases (e.g., gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) as opposed to hepatic metabolism which is particularly amenable to interference. Gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin are essentially not associated with clinically significant pharmacokinetic interactions. Of the new AEDs, lamotrigine and topiramate are the most interacting. Furthermore, the metabolism of lamotrigine is susceptible to both enzyme inhibition and enzyme induction. While the metabolism of felbamate, tiagabine, topiramate and zonisamide can be induced by enzyme-inducing AEDs, they are less vulnerable to inhibition by valproate. Noteworthy is the fact that only five new AEDs (eslicarbazepine, felbamate, oxcarbazepine, rufinamide and topiramate) interact with oral contraceptives and compromise contraception control. The most clinically significant pharmacodynamic interaction is that relating to the synergism of valproate and lamotrigine for complex partial seizures. Compared with the first-generation AEDs, the new second- and third-generation AEDs are less interacting, and this is a desirable development because it allows ease of prescribing by the physician and less complicated therapeutic outcomes and complications for patients.

Authors+Show Affiliations

Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Oslo, Norway.No affiliation info available

Pub Type(s)

Historical Article
Journal Article
Review

Language

eng

PubMed ID

20021326

Citation

Johannessen Landmark, Cecilie, and Philip N. Patsalos. "Drug Interactions Involving the New Second- and Third-generation Antiepileptic Drugs." Expert Review of Neurotherapeutics, vol. 10, no. 1, 2010, pp. 119-40.
Johannessen Landmark C, Patsalos PN. Drug interactions involving the new second- and third-generation antiepileptic drugs. Expert Rev Neurother. 2010;10(1):119-40.
Johannessen Landmark, C., & Patsalos, P. N. (2010). Drug interactions involving the new second- and third-generation antiepileptic drugs. Expert Review of Neurotherapeutics, 10(1), pp. 119-40. doi:10.1586/ern.09.136.
Johannessen Landmark C, Patsalos PN. Drug Interactions Involving the New Second- and Third-generation Antiepileptic Drugs. Expert Rev Neurother. 2010;10(1):119-40. PubMed PMID: 20021326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug interactions involving the new second- and third-generation antiepileptic drugs. AU - Johannessen Landmark,Cecilie, AU - Patsalos,Philip N, PY - 2009/12/22/entrez PY - 2009/12/22/pubmed PY - 2010/3/2/medline SP - 119 EP - 40 JF - Expert review of neurotherapeutics JO - Expert Rev Neurother VL - 10 IS - 1 N2 - During the period 1989-2009, 14 new antiepileptic drugs (AEDs) were licensed for clinical use and these can be subdivided into new second- and third-generation AEDs. The second-generation AEDs comprise felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. The third-generation AEDs comprise eslicarbazepine acetate and lacosamide. The interaction propensity of AEDs is very important because all new AEDs are licensed, at least in the first instance, as adjunctive therapy. The present review summarizes the interactions (pharmacokinetic and pharmacodynamic) that have been reported with the newer AEDs. The pharmacokinetic interactions include those relating to protein-binding displacement from albumin in blood, and metabolic inhibitory and induction interactions occurring in the liver. Overall, the newer AEDs are less interacting because their pharmacokinetics are more favorable and many are minimally or not bound to blood albumin (e.g., eslicarbazepine, felbamate, gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) and are primarily renally excreted or metabolized by noncytochrome P450 or uridine glucoronyl transferases (e.g., gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) as opposed to hepatic metabolism which is particularly amenable to interference. Gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin are essentially not associated with clinically significant pharmacokinetic interactions. Of the new AEDs, lamotrigine and topiramate are the most interacting. Furthermore, the metabolism of lamotrigine is susceptible to both enzyme inhibition and enzyme induction. While the metabolism of felbamate, tiagabine, topiramate and zonisamide can be induced by enzyme-inducing AEDs, they are less vulnerable to inhibition by valproate. Noteworthy is the fact that only five new AEDs (eslicarbazepine, felbamate, oxcarbazepine, rufinamide and topiramate) interact with oral contraceptives and compromise contraception control. The most clinically significant pharmacodynamic interaction is that relating to the synergism of valproate and lamotrigine for complex partial seizures. Compared with the first-generation AEDs, the new second- and third-generation AEDs are less interacting, and this is a desirable development because it allows ease of prescribing by the physician and less complicated therapeutic outcomes and complications for patients. SN - 1744-8360 UR - https://www.unboundmedicine.com/medline/citation/20021326/Drug_interactions_involving_the_new_second__and_third_generation_antiepileptic_drugs_ L2 - http://www.tandfonline.com/doi/full/10.1586/ern.09.136 DB - PRIME DP - Unbound Medicine ER -