Choice of initial antiepileptic drug for older veterans: possible pharmacokinetic drug interactions with existing medications.
OBJECTIVE
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.


METHODS
Five-year retrospective cohort study of veterans with new-onset epilepsy.


METHODS
National Veterans Affairs and Medicare databases.


METHODS
Veterans aged 66 and older with a new diagnosis of epilepsy between October 1, 1999, and September 30, 2004 (N=9,682).


METHODS
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).


CONCLUSIONS
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.
Pugh
Mary Jo V
MJ
South Texas Veterans Health Care System, VERDICT REAP, San Antonio, Texas 78229, USA. pughm@uthscsa.edu
Vancott
Anne C
AC
Steinman
Michael A
MA
Mortensen
Eric M
EM
Amuan
Megan E
ME
Wang
Chen-Pin
CP
Knoefel
Janice E
JE
Berlowitz
Dan R
DR
D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D015897:Comorbidity; D004347:Drug Interactions; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D019338:Polypharmacy; D014481:United States / Q000453:epidemiology; D014728:Veterans
D000927:Anticonvulsants
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