Antiepileptic drug interactions - principles and clinical implications.

Article Details

Citation

Johannessen SI, Landmark CJ

Antiepileptic drug interactions - principles and clinical implications.

Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254.

PubMed ID
21358975 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AprobarbitalCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
FelbamateCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
FosphenytoinCytochrome P450 1A2ProteinHumans
Unknown
Inducer
Details
PhenytoinCytochrome P450 1A2ProteinHumans
No
Inducer
Details
PhenytoinCytochrome P450 2C9ProteinHumans
No
Substrate
Inhibitor
Inducer
Details
PhenytoinCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
PrimidoneCytochrome P450 1A2ProteinHumans
Unknown
Inducer
Details
PrimidoneUDP-glucuronosyltransferases (UGTs) (Protein Group)Protein groupHumans
Unknown
Inducer
Details
Drug Interactions
DrugsInteraction
Albendazole
Phenytoin
The serum concentration of the active metabolites of Albendazole can be reduced when Albendazole is used in combination with Phenytoin resulting in a loss in efficacy.
Albendazole
Fosphenytoin
The serum concentration of the active metabolites of Albendazole can be reduced when Albendazole is used in combination with Fosphenytoin resulting in a loss in efficacy.
Bazedoxifene
Phenytoin
The serum concentration of Bazedoxifene can be decreased when it is combined with Phenytoin.
Bazedoxifene
Fosphenytoin
The serum concentration of Bazedoxifene can be decreased when it is combined with Fosphenytoin.
Carbamazepine
Magnesium salicylate
Magnesium salicylate can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Carbamazepine
Bentoquatam
Bentoquatam can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Carbamazepine
Magnesium oxide
Magnesium oxide can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Carbamazepine
Kaolin
Kaolin can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Carbamazepine
Zinc
Zinc can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Carbamazepine
Zinc trihydroxide
Zinc trihydroxide can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
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