This drug is not recommended during pregnancy and in patients of childbearing potential not using appropriate contraception; this drug should be used during pregnancy only if clearly needed and the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Based on animal data, this drug may cause fetal harm; no adequate data available on the developmental risk associated with use of this drug (or dimethyl fumarate [same active metabolite as this drug]) in pregnant women.

Comments:
-Patients should be advised to inform their health care provider if they are pregnant or plan to become pregnant during therapy.

Animal studies have revealed evidence of embryofetal toxicity, teratogenicity, and embryofetal lethality; adverse embryofetal effects were likely secondary to maternal toxicity. After oral doses (up to 400 mg/kg/day) to pregnant rats throughout organogenesis, decreased fetal body weight, increased fetal skeletal variations, and maternal toxicity were seen at the highest dose tested; plasma exposures (AUC) for monomethyl fumarate (MMF; active metabolite) and 2-hydroxyethyl succinimide (HES; inactive metabolite [the major circulating drug-related compound in humans]) at the no-effect dose (100 mg/kg/day) for adverse effects on embryofetal development were about 2 times those in humans at the maximum recommended human dose (MRHD). After oral doses (up to 350 mg/kg/day) to pregnant rabbits throughout organogenesis, increased fetal skeletal malformations and maternal toxicity were seen at the mid and high doses, and reduced fetal body weight, increased embryofetal death, and increased fetal skeletal variations were seen at the highest dose tested; plasma exposures (AUC) for MMF and HES at the no-effect dose (50 mg/kg/day) for adverse effects on embryofetal development were similar to (1.4 times) or less than (0.7 times), respectively, those in humans at the MRHD. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the child; caution is recommended.

Excreted into human milk: No (as parent drug); Yes (as active metabolite [monomethyl fumarate])

Comments:
-No information is available on the clinical use of this drug during breastfeeding.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered. A risk to newborns/infants cannot be excluded.
-Amounts of monomethyl fumarate in breast milk appear low and would not be expected to cause any adverse effects in breastfed infants.
---Breastfed infants should be monitored for adequate weight gain and developmental milestones, especially younger, exclusively breastfed infants.
---Some experts also recommend monitoring breastfed infants for flushing, vomiting, and diarrhea.

This drug is not found in plasma as it is rapidly converted to the active metabolite, monomethyl fumarate, which has a half-life of about 1 hour.

The closely related drug, dimethyl fumarate (240 mg orally twice a day), was started in 2 nursing mothers with relapsing-remitting multiple sclerosis after breastfeeding was discontinued; they continued pumping milk and on day 8 of therapy, they each provided milk samples at 1, 2, 4, 8, and 12 hours after dosing. Peak monomethyl fumarate milk levels were 3.7 mcg/L in 1 mother and 11.2 mcg/L in the other and occurred at about 2 hours after dosing; milk levels averaged 2.7 and 7.5 mcg/L, respectively. These values indicate that the infants would receive about 0.8 and 1.13 mcg/kg/day, respectively, or weight-adjusted relative infant dosages of 0.007% and 0.019% of the maternal dosage.

See references