Endocrine/Metabolic Agent (Hyperammonemia)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of carglumic acid in human pregnancy have been located. Although the animal data suggested risk when the drug was used from organogenesis through postpartum day 21, a portion of the risk may have reflected exposure during nursing (see Breastfeeding Summary). Women with N-acetylglutamate synthase (NAGS) deficiency must remain on treatment throughout pregnancy to prevent irreversible neurologic damage and death. If a pregnant woman does require this therapy, she should be informed of the absence of human pregnancy experience.
FETAL RISK SUMMARY
Carglumic acid is a structural analog of N-acetylglutamate available as oral tablets. It is indicated as adjunctive therapy for the treatment of acute and chronic hyperammonemia due to the deficiency of the hepatic co-enzyme NAGS. The agent is partially metabolized in the gut before absorption. Plasma protein binding has not been determined. The median terminal half-life is 5.6 hours (1).
Reproduction studies have been conducted in rats and rabbits. In these species, oral doses up to 1.3 times the maximum recommended human starting dose based on BSA (MRHSD) resulted in maternal toxicity, but no effects on embryo–fetal development were observed. When female rats received doses up to 1.3 times the MRHSD from organogenesis through day 21 postpartum, a reduction in offspring survival was seen at the highest dose and a reduction in offspring growth was seen at all doses (1).
Carcinogenicity studies have not been conducted with carglumic acid, but the drug was not mutagenic in multiple assays. No effects on fertility or reproductive performance were noted in female rats at doses up to 1.3 times the MRHSD, or mating or fertility in male rats at doses up to 0.6 times the MRHSD (1).
It is not known if carglumic acid crosses the human placenta. The molecular weight (about 190) and moderately long terminal half-life suggest that the drug will cross to the embryo–fetus. However, ionization at physiologic pH could limit the exposure.
BREASTFEEDING SUMMARY
No reports describing the use of carglumic acid during human lactation have been located. The molecular weight (about 190) and moderately long terminal half-life (5.6 hours) suggest that the drug will be excreted into breast milk, but ionization at physiologic pH could limit the exposure. The effect of the exposure on a nursing infant is unknown. However, the drug is excreted into rat milk, resulting in increased mortality and impaired body weight gain (1).
Reference
1.Product information. Carbaglu. Accredo Health Group, 2010.