Benefit should outweigh risk

AU TGA pregnancy category: B1
US FDA pregnancy category: C

Risk Summary: There are no adequate and well controlled studies in pregnant women; in rabbit studies, a rare defect, holoprosencephaly, was observed in rabbits dosed at 10 times the recommended human dose during organogenesis.

Comments:
-Uncontrolled phenylalanine (Phe) levels above 600 micromol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies.
-Good dietary control of Phe levels prior to and during pregnancy are essential; this drug should be considered only if dietary restriction of Phe is ineffective.

In rats, oral doses up to 3 times the maximum recommended human dose (MRHD) administered during the period of organogenesis failed to reveal clear evidence of teratogenic activity; however, in a rabbit study, doses of 10 times the MRHD were associated with a non-statistically significant increase in the incidence of holoprosencephaly; holoprosencephaly occurred in 2 treated litters compared to 1 control-treated litter. Available data from the Maternal Phenylketonuria Collaborative Study (n=468 pregnancies and 331 live births) showed that uncontrolled Phe levels above 600 micromol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies. There are no controlled data in human pregnancy.

US: To monitor the outcomes of pregnant women exposed to this drug, a patient registry has been established. For additional information: 1-800-983-4587

AU TGA pregnancy category B1: 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 not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

See references

It is not known whether this drug or its metabolites are excreted in human breastmilk. In rat studies, this drug was observed in rat milk after IV administration, however, no increase was observed after oral administration.

Benefit should outweigh risk

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this drug and any potential adverse effects on the infant from the drug or from the underlying maternal condition.
-Some authorities (AU and UK) recommend against use during breastfeeding.

See references