Metabolic (Enzyme Cofactor)
PREGNANCY RECOMMENDATION:Limited Human Data—Animal Data Suggest Low Risk (Maternal Benefit May Outweigh Any Embryofetal Risk)
BREASTFEEDING RECOMMENDATION:Probably Compatible
Five reports describing 32 patients using sapropterin either before or during pregnancy were identified. No embryofetal adverse effects were attributable to the therapy. The drug is likely to cross the placenta, so some fetal exposure will probably occur. However, this limited human pregnancy experience prevents a complete assessment of embryofetal risk. Animal studies did not show any embryofetal toxicity in two species at doses of less than 10 times the recommended human dose (RHD) in one and at 10 times the RHD in the second. Using this drug during pregnancy should be based on the pros and cons of the mother’s clinical need for treatment versus any potential fetal risk that might occur from exposure. The risk of uncontrolled phenylketonuria (PKU) is much greater to the embryo and/or fetus. If diet alone is not adequate to control maternal phenylalanine concentrations, the use of sapropterin appears to be a reasonable option. However, in clinical trials with nonpregnant adults, only about 40% of patients with PKU on average responded to treatment with sapropterin. Elevated phenylalanine levels are associated with developmental delays, microcephaly, congenital heart defects, growth delay, and seizures. The manufacturer recommends that phenylalanine levels should be maintained between 168 and 504 mcg/mL 3 months prior to conception and during pregnancy. ACOG recommends levels less than 600 mcg/mL for at least 3 months prior to conception and 200 to 600 mcg/mL during pregnancy. ACOG states that sapropterin may be an appropriate adjunct to dietary modification during pregnancy and breastfeeding.
The manufacturer reports that 16 women using sapropterin during lactation were identified from postmarketing registries. These women breastfed their infants for a mean of 3 to 4 months, and no lactation-related safety concerns were reported. In another case, the mother used sapropterin during pregnancy and through 25 months of lactation. The infant had normal development. Breastfeeding while using this drug should be based on the mother’s clinical need for treatment versus any potential infant risks that might occur. If used, the infant should be monitored for the most common reported adult side effects of headache and pharyngeal pain (both leading to irritability), rhinorrhea, diarrhea, vomiting, cough, and nasal congestion.