What causes flushing with Tecfidera?

40% of people report flushing as a side effect of Tecfidera and although experts aren’t sure how Tecfidera causes flushing they suggest it may be due to one of the pathways affected by Tecfidera called HCAR2. When the metabolite of Tecfidera, MMF binds to HCAR2, it induces prostanoid-forming enzymes in different cell types. These enzymes form prostaglandins which, in addition to other effects, signal capillaries to open, which causes flushing.

The incidence of flushing with Tecfidera can be greatly reduced by:

• Taking Tecfidera with food. Research has shown taking Tecfidera with food reduced the incidence of flushing by about 25%
• Taking a small dose of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes before taking Tecfidera. Aspirin reduces prostaglandin synthesis which reduces flushing.

Flushing is one of the most common side effects of Tecfidera with symptoms may include a feeling of warmth, redness, itching, and/or a burning sensation. These symptoms generally begin soon after initiating Tecfidera and usually improve or resolve over time. For most patients, symptoms are mild or moderate but less than 1% have serious flushing symptoms that led to hospitalization. 3% discontinue Tecfidera because of flushing.

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How does Tecfidera cause flushing?

Experts are not sure exactly how Tecfidera (dimethyl fumarate) causes flushing but they know it has antioxidant and immunomodulating (affecting the immune system) properties.

The antioxidant potential of Tecfidera appears to be mediated through two different pathways, one being the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is activated during oxidative stress. The other pathway involves a receptor for nicotinic acid/niacin and HCAR2.

HCAR2 is thought to be involved in the flushing reaction. When the metabolite of Tecfidera, monomethyl fumarate (MMF) binds to HCAR2, it induces prostanoid forming enzymes in different cell types. These enzymes form prostaglandins which signal capillaries to open, which causes flushing. Taking aspirin reduces prostaglandin synthesis which reduces flushing.