Alcohol May Interfere With Tecfidera Metabolism, Study Finds

Consuming alcohol inhibits a liver enzyme necessary to break down DMF to MMF

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Consuming alcohol around dosing time could limit the effectiveness of Tecfidera (dimethyl fumarate) for multiple sclerosis patients, a recent study suggests.

Results from the study, which involved lab and mouse experiments, showed alcohol inhibits an enzyme in the liver that’s necessary to break down Tecfidera’s main ingredient, dimethyl fumarate (DMF) to its active metabolite, monomethyl fumarate (MMF). When alcohol was present, MMF – which drives Tecfidera’s therapeutic effects – was completely absent in the mice’s blood and brain tissue.

“It is recommended based on this study that alcohol consumption be avoided in close temporal proximity to dosing with DMF to avoid this interaction,” the study’s researchers wrote, noting additional studies in humans are still needed.

The study, “Alcohol inhibits the metabolism of dimethyl fumarate to the active metabolite responsible for decreasing relapse frequency in the treatment of multiple sclerosis,” was published in PLOS One.

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Biogen‘s Tecfidera and a number of generic versions are approved for treating relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS.

Once ingested, inactive DMF is completely converted to its active form, MMF. As such, it’s thought DMF is so scant in the bloodstream after the medication is taken that it’s unable to be measured and MMF is present instead.

While MMF’s therapeutic mechanism isn’t fully known, its thought to work by altering the activity of immune cells that drive inflammation in MS.

Research suggests the metabolism of DMF to MMF is mediated by certain enzymes in the intestines or liver, but which enzymes involved haven’t been established. And while it’s thought that alcohol may interfere with Tecfidera, especially in the first hour after taking it, it hadn’t been established whether it may specifically disrupt the enzymes needed to break DMF down, leading researchers in Tennessee to learn which enzymes are responsible for DMF metabolism and if their activity is influenced by alcohol.

The researchers first incubated DMF with certain candidate enzymes, which showed it was significantly metabolized to MMF in the presence of one in particular enzyme, called carboxylesterase-1 (CES1). This enzyme is predominately found in the liver, whereas others largely found in the intestines had no discernible effects.

When alcohol was added to the mix, CES1 activity was inhibited and the conversion of DMF to MMF was reduced, however.

Mice also show reduced MMF concentrations with alcohol

The researchers then administered either alcohol or a placebo to mice, followed 10 minutes later by a 100 mg/kg dose of DMF. The mice were genetically engineered to have more human-like processes to drug metabolism.

As in the lab studies, MMF concentrations were reduced in the blood of animals that received alcohol. In turn, DMF concentrations were higher, reflecting the inhibition of DMF’s conversion to MMF with alcohol.

Alcohol exposure also led to drastic reductions of MMF in brain tissue, but DMF levels were not as high in the brain as in the blood.

“Collectively, these results predict that the most likely outcome of the consumption of alcohol with a DMF dose will be a decrease in exposure to the MMF active metabolite leading to reduced efficacy,” the researchers wrote.

The findings are particularly relevant given that consuming alcohol is common among MS patients, with more than 60% reporting that they drink at least small amounts.

“Thus, the interaction of DMF with alcohol is expected to be a common occurrence in people with [MS] taking this medication twice daily,” the researchers wrote, noting that, while their findings need to be confirmed in people, previous research with other medications suggest results will line up with the preclinical data.

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