Benefit should outweigh risk.
-According to some authorities: Use is not recommended unless clearly needed.

AU TGA Pregnancy Category: D
US FDA pregnancy category: Not assigned.

Risk summary: Based on animal studies, this drug may cause fetal harm; there is limited available data to inform a drug-associated risk of adverse developmental outcomes in humans. There are known fetal risks associated with poorly controlled phenylalanine concentrations in women during pregnancy.

Comments:
-It is suggested to monitor phenylalanine concentrations during pregnancy in women with phenylketonuria (PKU); blood phenylalanine concentrations should be maintained between 120 and 360 micromol/L during pregnancy and in the 3 months before conception.
-If phenylalanine concentrations fall below 30 micromol/L during pregnancy, it is suggested to adjust dose and/or modify dietary protein and phenylalanine intake.
-Pregnant women and those of reproductive potential should be advised of the risks to a fetus with this drug.
-A pregnancy exposure registry is available.

Animal studies have revealed evidence of teratogenicity and embryofetal toxicity at doses associated with maternal toxicity. The following studies were conducted in animals without PKU. In each study, maternal toxicity was associated with the studied doses; for doses that produced maternal toxicity, the maternal plasma phenylalanine concentrations were markedly reduced compared to the control group. The contribution of these markedly reduced maternal phenylalanine levels to the incidence of embryo-fetal developmental effects was not evaluated. In pregnant rabbits receiving 5 times the maximum recommended daily dose, a high incidence of fetal malformations throughout the skeletal system, in the kidneys, lungs, and eyes; and embryo-fetal toxicity including increased resorptions and reduced fetal weight were observed. In pregnant rats receiving 2.8 times the maximum recommended daily dose, increased skeletal variations with no malformations were observed. In a pre- and post-natal study in rats at 13 times the maximum recommended daily dose, reduced offspring survival during lactation, decreased pup weight and litter size, and delayed sexual maturation of offspring were observed. In women, uncontrolled phenylalanine concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes. Available data from the Maternal Phenylketonuria Collaborative Study (n=468 pregnancies; 331 live births in women with PKU) have shown that phenylalanine concentrations above 600 micromol/L are associated with an increased risk for miscarriage, major birth defects (including microcephaly, major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ. There are no controlled data in human pregnancy.

To monitor the outcomes of pregnant women exposed to this drug (during pregnancy or within 1 month after the last dose), a pregnancy registry has been established. Health care providers should report such exposure by calling 1-866-906-6100.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

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

If this drug was to be present in human milk, it may lower phenylalanine concentrations. Although there is no information on the use of this drug during breastfeeding, the amounts in milk appear to be trivial and absorption by the infant from breastmilk is unlikely, as it is a polypeptide that is probably destroyed in the infant's gastrointestinal tract.

Benefit should outweigh risk.

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

Comments:
-It is suggested to monitor blood phenylalanine concentrations in breastfeeding women.
-There are no data on the effects of this drug on the breastfed infant or its effects on milk production.
-The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects to the breastfed infant from the drug or from the underlying maternal condition.

See references