Abstracts

Rationale: Many traditional, older antiepileptic drugs (AEDs) are broad spectrum inducers of hepatic and intestinal CYP enzymes. Concomitant administration with enzyme-inducing AEDs (EIAED) may result in kinetic interactions that may compromise the efficacy of other medications a patient may be receiving, such as a statin. While PK interactions between EIAEDs and several statins are well recognized, clinical outcomes have yet to be studied beyond a small cohort of patients. Our objective therefore was to characterize the effect of EIAEDs, versus non-enzyme inducing anti-epileptic medications (NEIAED) on lipid control and required statin dose in patients with epilepsy. Methods: A retrospective chart review of patients concurrently prescribed an AED along with a statin was performed. Patients were divided by those prescribed an EIAED versus solely NEIAEDs. Clinical endpoints included most recent LDL level on concurrent therapy, as well as proportion of patients with LDL reaching goal and the required atorvastatin-normalized statin dose. Eligible patients included those receiving a stable dose of an AED, at least one LDL value at least 3 months after the first instance of concurrent AED/statin co-prescription. Patients were excluded if receiving any other CYP450 inducers or inhibitors or pravastatin. Statistical analysis included T-tests and chi-square for continuous and categorical variables, respectively. Linear regression was used to evaluate the difference in LDL values while minimizing the effects of confounding variables (age, sex, BMI, number of concomitant LDL lowering medications, and adherence to both statins and AEDs). Results: Of 219 records reviewed, 82 were excluded based on the pre-defined exclusion criteria. Of those receiving EIAED (n=64) phenytoin was the most frequently prescribed (62.5%), followed by carbamazepine (34.4%). In the NEAED (n=73), levetiracetam (69.9%) followed by lamotrigine (30.1%) were the most commonly used agents. Baseline characteristics of these groups were similar (sex, age, BMI, co-morbidities diabetes, CAD, CAD risk equivalent, medication adherence). Treatment with an EIAED was associated with a 12.6 mg/dl higher mean LDL after controlling for the aforementioned covariates (p<0.003). The EIAED group also had higher total cholesterol (170 mg/dl vs. 156 mg/dl, p<0.02), and higher HDL (54 mg/dl vs. 48 mg/dl, p<0.04)). Interestingly, although both groups were similar in achieving LDL targets (EIAED: 79.7% vs NIAED: 83.6%, p=NS); as compared to patients prescribed NEIAEDs, patients prescribed an EIAED were receiving significantly higher atorvastatin-normalized statin doses (44.8 mg/d vs. 28.9/d mg, p<0.04). Conclusions: These data support the notion that PK interactions with enzyme inducers may likely result in less than optimal therapeutic outcomes. Clinicians should be mindful that in the presence of EIAEDs, more attention to routine dosages of concomitant medication may be required.