Fumaric acid has been shown to be well tolerated over the many decades it has been used to treat psoriasis, with over 50,000 patient-years of safety information recorded. In one study of people with psoriasis who had received the medication for up to 14 years, the most common adverse effects included flushing, diarrhea, and nausea. However, Tecfidera (also known as BG12), as a second-generation fumaric acid medication, was formulated to reduce gastrointestinal or GI effects. During the Phase 2b study, the most common adverse effects included flushing, headaches, and GI symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. These GI symptoms tended to decrease over time, with continued treatment. Elevations in liver enzymes were also reported in people receiving Tecfidera.
Adverse effects in Phase 3 studies
The safety of Tecfidera was evaluated in the Phase 3 studies DEFINE and CONFIRM, which included a combined 1,529 patients with an overall drug exposure of over 2,000 person-years. Adverse effects that occurred at a higher rate in patients receiving Tecfidera compared with placebo included lymphopenia (2% vs <1%), abdominal pain (18% vs 10%), diarrhea (14% vs 11%), flushing (40% vs 6%), severe itching (pruritis) (8% vs 4%), rash (8% vs 3%), and selected laboratory tests.
Adverse effects in Phase 3 studies: Tecfidera vs placebo
Tecfidera 240 mg
|Albumin in urine||6%||4%|
Warnings and precautions with Tecfidera
In clinical trials conducted in patients with MS, Tecfidera resulted in decreased lymphocyte counts by about 30% during the first year. Counts then remained stable subsequently. When Tecfidera was stopped, lymphocyte counts increased. However, they did not return to pre-treatment levels. When lymphocyte counts (lymphocytes are white blood cells that play an important role in the immune system) drop below normal, it is called lymphopenia or lymphocytopenia.
Because Tecfidera can cause lymphopenia, before you start taking Tecfidera, and periodically (annually) while you are taking the drug, your doctor will test your blood to determine whether you have normal levels of lymphocytes. You should have normal lymphocyte counts before you start receiving Tecfidera and while you are taking the drug. Your doctor may decide to withhold treatment with Tecfidera if you develop a serious infection while taking the drug.
In clinical trials conducted in patients with MS, Tecfidera resulted in flushing (this includes warmth, redness, itching, and/or burning) in 40% of patients. This adverse effect improved shortly after starting treatment and the effect was of mild-to-moderate severity in most patients. Only 3% of patients discontinued taking Tecfidera due to flushing and less than 1% experienced serious flushing. Taking Tecfidera with food may reduce the risk of flushing.
Pregnancy and lactation
There are to date no adequate studies of the safety of Tecfidera in pregnant women to determine whether the drug may cause adverse effects on the developing fetus. Therefore, Tecfidera should only be used during pregnancy if the potential benefits outweigh any possible risks. Speak to your doctor before starting Tecfidera if you are planning to become pregnant, or if you become pregnant while taking Tecfidera.
It is not known whether Tecfidera is secreted into human breast milk, so speak to your doctor before taking Tecfidera if you are nursing.