Dimethyl Fumarate and Breastfeeding

Summary of use during lactation

The active form of both dimethyl fumarate and diroximel fumarate is monomethyl fumarate. Amounts of monomethyl fumarate in breastmilk appear to be low and would not be expected to cause any adverse effects in breastfed infants. Clinical data in over 20 infants indicates that it is acceptable to use during breastfeeding, at least after one month of age. Breastfed infants should be monitored for adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants. Some authors also recommend monitoring breastfed infants for flushing, vomiting and diarrhea.[1,2]

Drug levels in milk and infant serum

Dimethyl fumarate is not found in the plasma because it is rapidly converted to the active drug, monomethyl fumarate, which has a half-life of about 1 hour. Maternal Levels. Two nursing mothers with relapsing-remitting multiple sclerosis began oral dimethyl fumarate 240 mg twice daily after discontinuing breastfeeding. They continued pumping milk and on day 8 of therapy, they each provided milk samples at 1, 2, 4, 8 and 12 hours after a dose. Peak monomethyl fumarate milk levels were 3.7 mcg/L in one mother and 11.2 mcg/L in the other and occurred at about 2 hours after the dose. Average milk levels were 2.7 mcg/L and 7.5 mcg/L, respectively. These values indicate that the infants would receive daily dosages of about 0.8 mcg/kg and 1.13 mcg/kg, respectively, or weight-adjusted relative infant dosages of 0.007% and 0.019% of the maternal dosage.[2] A woman with multiple sclerosis who was 3 months postpartum began dimethyl fumarate 120 mg (Polpharma SA Pharmaceutical works, Starogard Gdański, Poland) orally twice daily after weaning her infant. Four milk samples were collected over a 24-hour period 6 days after starting therapy. The concentration of monomethyl fumarate ranged from 83.5 mcg/L just after a dose to undetectable (<5.5 mcg/L) at 2 hours before the next dose. The authors estimated a daily dose of 5.76 mcg/kg with a daily milk intake of 150 mL/kg, which represents a relative infant dose of 0.16%.[3] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

Twenty-six women taking dimethyl fumarate for relapsing-remitting multiple sclerosis were followed during 29 pregnancies from 2015 to 2020. Dimethyl fumarate was administered through week 24 of pregnancy and resumed 1 month after delivery. Twenty-two of 26 mothers breastfed (extent not stated) for 4 to 7 months. Infants were monitored up to the third year of life for infections and developmental disorders. All children were the 70th and 95th percentile for height and weight. The authors concluded that continuing dimethyl fumarate while breastfeeding is safe,[4] although infants were not exposed during the first month of life. One group reported two mothers with multiple sclerosis who resumed taking dimethyl fumarate 1 week after delivery while partially breastfeeding their infants. One was taking 240 mg daily and withheld breastfeeding for 4 hours after each dose. The other was taking 480 mg daily with mixed feeding continuing for 15 months. The latter patient became pregnant again and once again used mixed feeding while taking dimethyl fumarate. All 3 infants developed normally and had no serious infections.[5]

Effects on lactation and breastmilk

Relevant published information was not found as of the revision date.

Alternative drugs to consider

(Multiple Sclerosis) Glatiramer, Immune Globulin, Interferon Beta

References

1. Almas S, Vance J, Baker T, et al. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int 2016;2016:6527458.26966579 PubMed
2. Ciplea AI, Datta P, Rewers-Felkins K, et al. Dimethyl fumarate transfer into human milk. Ther Adv Neurol Disord 2020;13:x.33193814 PubMed
3. Van Neste M, Nauwelaerts N, Ceulemans M, et al. Very low monomethyl fumarate exposure via human milk: A case report—a contribution from the ConcePTION project. Front Public Health 2024;12:1393752. doi:10.3389/fpubh.2024.139375239015385 PubMed
4. Borriello G, Ianniello A. Efficacy, safety and tolerability of dimethylfumarate during pregnancy and breastfeeding. Mult Scler Relat Disord 2022;67:103949. doi:10.1016/j.msard.2022.103951
5. Saito S, Ikeguchi R, Kitagawa K, et al. Clinical experience with dimethyl fumarate and natalizumab in pregnant women with multiple sclerosis: A four-patient case series. Case Rep Neurol Med 2024;2024:7808140.39044765 PubMed