Tecfidera Found in Breast Milk But Levels Appear Safe, Case Study Reports

Tecfidera (dimethyl fumarate) was detected in the breast milk of two women using the oral therapy to treat their multiple sclerosis, but at concentrations well below the “theoretical threshold of concern” for an infant, a case study reported.

According to its investigators, this is the first evidence of Tecfidera’s transfer to the breast milk of relapsing-remitting multiple sclerosis (RRMS) patients, and levels found there — even at peak concentration — were acceptably low and not accumulating, suggesting Tecfidera might be compatible with breastfeeding.

Larger and more extensive studies are needed for confirmation, they added.

The case study, “Dimethyl fumarate transfer into human milk,” was published in the journal Therapeutic Advances in Neurological Disorders.

Tecfidera, marketed by Biogen, is an oral medication that reduces MS exacerbations and flares by modulating the immune response. It is widely approved as a first-line treatment of RRMS, including across Europe, and for all relapsing forms of MS in the U.S.

Following intake, Tecfidera is metabolized into the active metabolite monomethyl fumarate (MMF). Its safety while breastfeeding and the risk of MMF transfer to the infant through breast milk are unknown, and patients taking Tecfidera are advised either to assess risks and benefits or to discontinue the therapy.

Researchers in Germany sought to determine if MMF is excreted into breast milk at a concentration harmful to the nursing infant.

Two RRMS patients, both breastfeeding mothers with the German MS and pregnancy registry, took part in their study. The women stopped breastfeeding when their disease required them to resume Tecfidera at a standard twice-daily oral dose of 240 mg.

They donated breast milk samples acquired through pumping. Samples were collected before the first Tecfidera dose in the postpartum period, and then repeatedly at eight days after restarting treatment at one, two, four, eight, and 12 hours after administration.

The first patient was a 35-year-old woman diagnosed with RRMS who restarted Tecfidera treatment after breastfeeding her daughter for almost six months.

An “MRI 6 months after delivery indicated new lesions, so she decided to wean her infant and restart oral Tecfidera (DMF) treatment. She continued to pump to retain her supply and donated milk samples for this study,” the researchers wrote.

The second patient, a 36-year-old with RRMS, breastfed her son for five months until new lesions were found and she restarted on Tecfidera.

Maximum MMF concentrations in milk varied between the two patients, with the first woman having considerably higher levels than the second — a maximum concentration of 11.23 ng/ml vs. 3.7 ng/ml — which the researchers associated to variability among patients. However, in both cases, peak MMF concentrations in breast milk was at two hours  after Tecfidera treatment.

The average MMF concentration for each patient was used to calculate the relative infant dose (RID), which estimates the nursing infant’s drug exposure through breast milk.

At 12 hours post-treatment, the RID was 0.019% for patient 1 and 0.007% for patient 2. Both RID calculations were considerably under the 10% theoretical threshold of concern for exposure-related adverse events.

“This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant,” the researchers wrote. “These data provide valuable information, assisting neurologists and patients in their decision-making process regarding treatment during lactation.”

The team, however, emphasized that although the results are encouraging, they should be viewed with caution due to the small sample size and the lack of analysis of maternal plasma levels, another indicator of drug concentration in breastmilk. The variability seen in MMF breast milk levels between these two women is also notable. 

“Low RIDs alone should not be automatically interpreted as being absolutely safe,” the researchers wrote. “Many other factors such as oral bioavailability [the proportion entering blood circulation] of the drug, and its overt toxicity in milk should also be considered.” 

Further and larger studies that included ” follow-up data on exposed breastfed infants are needed to confirm these findings,” the researchers concluded, “but our results suggest that DMF treatment might be compatible during lactation.”