BAFIERTAM SIDE EFFECTS

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Anaphylaxis and Angioedema.
• Progressive Multifocal Leukoencephalopathy.
• Herpes Zoster and Other Serious Opportunistic Infections.
• Lymphopenia.
• Liver Injury.
• Flushing.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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 practice.

The data described in the following sections were obtained using dimethyl fumarate delayed-release capsules (the prodrug of BAFIERTAM).

Adverse Reactions In Placebo-Controlled Trials With Dimethyl Fumarate

In the two well-controlled studies demonstrating effectiveness, 1529 patients received dimethyl fumarate with an overall exposure of 2244 person-years [see Clinical Studies].

The adverse reactions presented in Table 1 below are based on safety information from 769 patients treated with dimethyl fumarate 240 mg twice a day and 771 placebo-treated patients. The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for dimethyl fumarate were flushing, abdominal pain, diarrhea, and nausea.

Table 1: Adverse Reactions in Study 1 and 2 Reported for Dimethyl Fumarate at ≥ 2% Higher Incidence than Placebo

Gastrointestinal

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

Hepatic Transaminases

An increased incidence of elevations of hepatic transaminases in patients treated with dimethyl fumarate in clinical trials 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). Elevations of alanine aminotransferase and aspartate aminotransferase to ≥ 3 times the ULN occurred in a small number of patients treated with both dimethyl fumarate and in patients on placebo, and were balanced between the 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 dimethyl fumarate or placebo.

Eosinophilia

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

Adverse Reactions In Studies With BAFIERTAM (Monomethyl Fumarate)

In clinical studies, a total of 178 healthy subjects have received single doses of BAFIERTAM. The adverse reaction profile of BAFIERTAM was consistent with the experience in the placebo-controlled clinical trials with dimethyl fumarate. Taking BAFIERTAM without food may reduce the incidence of GI events.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of dimethyl fumarate (the prodrug of BAFIERTAM). 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 administration in postmarketing experience.

Herpes zoster infection and other serious opportunistic infections have been reported following administration in postmarketing experience.

SRC: NLM .