Choice of Initial Antiepileptic Drug for Older Veterans: Possible Pharmacokinetic Drug Interactions with Existing Medications

OBJECTIVES To identify clinically meaningful potential drug-drug interactions (PDIs) with antiepileptic drugs (AEDs), the AEDs and co-administered drugs commonly associated with AED-PDIs, and characteristics of patients with high likelihood of AED-PDI exposure. DESIGN Five-year retrospective cohort study of veterans with new-onset epilepsy. SETTING National Veterans Affairs and Medicare databases. PARTICIPANTS Veterans aged 66 and older with a new diagnosis of epilepsy between October 1, 1999, and September 30, 2004 (N=9,682). MEASUREMENTS AED-PDI was restricted to clinically meaningful PDIs identified using prior literature review. AED-PDIs were identified using participants' date of initial AED prescription and overlapping concomitant medications. Logistic regression analysis identified factors associated with AED-PDI, including demographic characteristics, chronic disease states, and diagnostic setting. RESULTS AED-PDI exposure was found in 45.5% (4,406/9,682); phenytoin, a drug with many PDIs, was the most commonly prescribed AED. Cardiovascular drugs, lipid-lowering medications, and psychotropic agents were the most commonly co-administered AED-PDI medications. Individuals with AED-PDI exposure were more likely to have hypertension (odds ratio (OR)=1.46, 99% confidence interval (CI)=1.24-1.82) and hypercholesterolemia (OR=1.40, 99% CI=1.24-1.57) than those without and to be diagnosed in an emergency or primary care setting than a neurology setting (emergency: OR=1.30, 99% CI=1.08-1.58; primary care: OR=1.29 99% CI=1.12-1.49). CONCLUSION Exposure to AED-PDI was substantial but less common in patients with epilepsy diagnosed in a neurology setting. Because potential outcomes associated with AED-PDI include stroke and myocardial infarction in a population already at high risk, clinicians should closely monitor blood pressure, coagulation, and lipid measures to minimize adverse effects of AED-PDIs. Interventions to reduce AED-PDIs may improve patient outcomes.