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

Abstract

Objectives Identify clinically-meaningful potential drug-drug interactions with antiepileptic drugs (AED-PDI), the AEDs and co-administered drugs commonly associated with AED-PDI, and characteristics of patients with increased likelihood of AED-PDI exposure. Design Five-year retrospective cohort study of veterans with new-onset epilepsy. Setting National VA and Medicare databases. Participants Veterans age 66 years and older with a new diagnosis of epilepsy between October 1, 1999-September 30, 2004 (N=9,682). Measurements We restricted AED-PDI to clinically-meaningful potential drug interactions identified by prior literature review. AED-PDI 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 potential drug interactions, was the most commonly prescribed AED. Cardiovascular drugs, lipid-lowering medications and psychotropic agents were the most commonly co-administered AED-PDI medications. Individuals at higher likelihood of AED-PDI exposure had 1) hypertension (OR=1.46, 99% CI 1.24-1.82), 2) hypercholesterolemia (OR=1.40, 99% CI 1.24-1.57) and 3) were diagnosed in emergency or primary care vs. Neurology settings (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 epilepsy patients diagnosed in a neurology setting. Because potential outcomes associated with AED-PDI include stroke and myocardial infarction in a population already at elevated risk, clinicians should closely monitor blood pressure, coagulation, and lipid measures to minimize adverse effects of AED-PDI. Interventions to reduce AED-PDI may improve patient outcomes.

Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy

“…Our finding that veterans with cerebrovascular disease (CVD) were more likely to receive levetiracetam may be due to their higher likelihood of receiving neurology specialty care and the need for an AED with minimal potential drug interactions [36]. In contrast, the lower likelihood of topiramate use in these veterans may be associated with concern regarding the potential cognitive adverse events of topiramate and reduced verbal fluency [37].…”

Newer antiepileptic drug use and other factors decreasing hospital encounters

“…Additional indicators of quality care are avoidance of enzyme-inducing drugs as first or second choices and avoidance of drug interactions, factors mainly associated with first-generation drugs. In a recent study of older veterans, it was noted that neurologists were more likely to consider drug interactions in selecting an AED [28]. However, physician expertise may be a separate factor from drug choice [4].…”

Epilepsy in the Elderly

“…Geriatric patients are undoubtedly vulnerable to drugedrug interactions. Potential drug interactions are seen in nearly half of elderly epilepsy patients and mostly seen in phenytoin between cardiovascular medications or psychotropic agents 66 . The newer AEDs without significant drug interactions (such as gabapentin, levetiracetam, pregabalin or low-dose lamotrigine) may be suitable to minimize this problem 67e69 .…”