Enzyme-Inducing Antiepileptic Drugs Increase Vitamin D Requirements in Epilepsy

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Investigators aimed to determine whether utilization of enzyme-inducing antiepileptic drugs increases vitamin D requirements.

The following article is part of conference coverage from the American Epilepsy Society’s Annual Meeting in New Orleans, LA. The Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.

Patients with epilepsy who take enzyme-inducing antiepileptic drugs (EIAEDs) require larger vitamin D supplement doses to achieve a similar plasma level of 25-OH vitamin D (25-OHD) as patients with epilepsy who take non-inducing antiepileptic drugs (NIAEDs), according to research presented at the 2018 American Epilepsy Society meeting held November 30-December 4, 2018 in New Orleans, Louisiana.

“It has been suggested that EIAEDs affect CYP450 isoenzymes, potentially increasing vitamin D metabolism, resulting in reduced 25-OH vitamin D (25-OHD) plasma levels,” the study researchers wrote. “It follows then that a potential pharmacokinetic interaction could exist between EIAEDs and oral formulations of vitamin D used for supplementation. Our objective was to characterize concomitant administration of antiepileptic drugs upon vitamin D dose requirements.”

Researchers from the University of Wisconsin and the William Middleton Memorial VA Hospital retrospectively reviewed medical charts of patients with epilepsy who were on any antiepileptic drug regimen and were prescribed a vitamin D supplement (n=315). Patients were stratified into 2 groups: patients taking an EIAED(s) and patients taking NIAEDs.

The investigators defined a minimum 25-OHD plasma level of 30 ng/ml to be the therapeutic goal. In addition, the researchers compared differences between the 2 treatment groups in the vitamin D dose required to reach the therapeutic goal.

A total of 1113 observations were obtained and retrospectively reviewed. Of the 263 observations in the EIAED group, approximately half of the patients took phenytoin (50.6%) whereas carbamazepine, phenobarbital, oxcarbazepine, primidone, and eslicarbazepine acetate were prescribed to 31.9%, 14.1%, 6.8%, 1.9%, and 0.8% of the patients, respectively.

No difference was observed between the groups in terms of 25-OHD levels, and both the EIAED and NIAED patient groups met the therapeutic goal levels (32 ng/ml vs 33.2 ng/ml, respectively; P =.28).

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The daily dose of vitamin D needed in patients taking EIAED was significantly higher (1587 units/d) than patients taking NIAED (1108 units/d). Results of the linear regression were consistent with the primary analysis with a 409-unit increase in vitamin D dose in the EIAED group (P =.052).

According to the researchers, the findings from this study suggest “that patients taking EIAEDs may benefit from more intensive monitoring of their vitamin D supplementation, and clinicians should anticipate this likely pharmacokinetic interaction.”

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Gidal BE, Menninga N, Koukounas Y, Margolis A, Breslow R. Impact of enzyme-inducing antiepileptic drugs on vitamin d dose requirements in veterans with epilepsy. Presented at: AES 2018; November 30-December 4, 2018; New Orleans, Louisiana. Abstract #1.315.