Side Effects of Tecfidera (dimethyl fumarate)

Tecfidera (dimethyl fumarate) is an oral disease-modifying agent used to treat relapsing forms of multiple sclerosis (MS). 

Although the exact mechanism of how Tecfidera works is unknown, it is thought to have protective effects on the nervous system and anti-inflammatory properties. Tecfidera prevents the immune cells from attacking the central nervous system. Tecfidera reduces the number of annual relapses rate. 

Common side effects of Tecfidera include

• flushing,
• abdominal pain,
• diarrhea, and
• nausea. 

Serious side effects of Tecfidera include

• decreased white blood cell counts and
• increased liver enzymes.

No potential drug interactions of Tecfidera were identified in clinical studies. 

There are no adequate data on the developmental risk associated with the use of Tecfidera in pregnant women. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Tecfidera during pregnancy.

It is unknown if Tecfidera is secreted into breast milk. Consult your doctor before breastfeeding. 

The most common side effects associated with dimethyl fumarate treatment are

• flushing,
• abdominal pain,
• diarrhea, and
• nausea.

A decrease in white blood cell count also occurs. Patients should check their baseline white blood cell count or have a recently completed blood cell count (CBC) (within 6 months) before starting treatment. Increase in liver enzymes has also been reported in clinical studies.

The following important adverse reactions are described elsewhere in labeling:

• Anaphylaxis and Angioedema
• Progressive multifocal leukoencephalopathy
• Lymphopenia
• Liver Injury
• Flushing

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for Tecfidera were

• flushing,
• abdominal pain,
• diarrhea, and
• nausea.

Adverse Reactions In Placebo-Controlled Trials

In the two well-controlled studies demonstrating effectiveness, 1529 patients received Tecfidera with an overall exposure of 2244 person-years.

The adverse reactions presented in the table below are based on safety information from 769 patients treated with Tecfidera 240 mg twice a day and 771 placebo-treated patients.

Table 1: Adverse Reactions in Study 1 and 2 reported for Tecfidera 240 mg BID at ≥ 2% higher incidence than placebo

Gastrointestinal

• Tecfidera caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia).
• The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with Tecfidera compared with placebo.
• Four percent (4%) of patients treated with Tecfidera and less than 1% of placebo patients discontinued due to gastrointestinal events.
• The incidence of serious GI events was 1% in patients treated with Tecfidera.

Hepatic Transaminases

• An increased incidence of elevations of hepatic transaminases in patients treated with Tecfidera was seen primarily during the first six months of treatment, and most patients with elevations had levels < 3 times the upper limit of normal (ULN) during controlled trials.
• Elevations of alanine aminotransferase and aspartate aminotransferase to ≥ 3 times the ULN occurred in a small number of patients treated with both Tecfidera and placebo and were balanced between groups.
• There were no elevations in transaminases ≥ 3 times the ULN with concomitant elevations in total bilirubin > 2 times the ULN. Discontinuations due to elevated hepatic transaminases were < 1% and were similar in patients treated with Tecfidera or placebo.

Eosinophilia

• A transient increase in mean eosinophil counts was seen during the first 2 months of therapy.

Adverse Reactions In Placebo-Controlled And Uncontrolled Studies

• In placebo-controlled and uncontrolled clinical studies, a total of 2513 patients have received Tecfidera and been followed for periods up to 4 years with an overall exposure of 4603 person-years.
• Approximately 1162 patients have received more than 2 years of treatment with Tecfidera.
• The adverse reaction profile of Tecfidera in the uncontrolled clinical studies was consistent with the experience in the placebo-controlled clinical trials.

Post Marketing Experience

• The following adverse reaction has been identified during post approval use of Tecfidera.
• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Liver function abnormalities (elevations in transaminases = 3 times ULN with concomitant elevations in total bilirubin > 2 times ULN) have been reported following Tecfidera administration in post marketing experience.

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