A mechanistic approach to antiepileptic drug interactions.
Article Details
- CitationCopy to clipboard
Anderson GD
A mechanistic approach to antiepileptic drug interactions.
Ann Pharmacother. 1998 May;32(5):554-63. doi: 10.1345/aph.17332.
- PubMed ID
- 9606477 [ View in PubMed]
- Abstract
OBJECTIVE: To describe the primary types of antiepileptic drug (AED) interactions by using a mechanistic approach. DATA SOURCES: A literature search was performed using MEDLINE and bibliographies of recent review articles and published abstracts. DISCUSSION: AEDs are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition and protein-binding displacement. Hepatic induction by AEDs affects the metabolism of a limited number of drugs with low therapeutic indices. Anticipation of induction interactions and careful clinical monitoring may alleviate potential problems. Most commonly used AEDs are eliminated through hepatic metabolism catalyzed by the cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) enzymes. Phenytoin, phenobarbital, and carbamazepine induce CYP and UGT enzymes. Lamotrigine is a weak inducer of UGT. Valproate is a broad-spectrum inhibitor of UGT enzymes, epoxide hydrolase, and CYP2C enzymes. Felbamate induces CYP3A4, but inhibits CYP2C19 substrates. Topiramate inhibits only CYP2C19 substrates. Ethosuximide, gabapentin, tiagabine, and vigabatrin are neither inducers nor inhibitors of drug metabolism. Hepatic enzyme inhibition usually occurs because of competition at the enzyme site. Knowledge of the specific metabolic enzymes involved in the metabolism of AEDs allows clinicians to predict potential interactions. CONCLUSIONS: By understanding the mechanisms of drug interactions, the pharmacist can play a key role in patient care by anticipating and preventing AED drug interactions.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Valproic acid Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareCanagliflozinPhenytoin The serum concentration of Canagliflozin can be decreased when it is combined with Phenytoin. CanagliflozinFosphenytoin The serum concentration of Canagliflozin can be decreased when it is combined with Fosphenytoin. CanagliflozinCarbamazepine The metabolism of Canagliflozin can be increased when combined with Carbamazepine.