Drugs in Pregnancy and Lactation: Tenth Edition

LARONIDASE

Endocrine/Metabolic Agent (Enzyme)

PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk

BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity (≤7 Days after Birth) Probably Compatible (>7 Days after Birth)

PREGNANCY SUMMARY

One report of laronidase in human pregnancy has been located, and that case involved exposure before the onset of organogenesis. The animal reproduction data, although based on body weight, suggest low risk. However, the absence of human pregnancy experience during organogenesis and later prevents a more complete assessment. Nevertheless, the benefits (improved pulmonary function and walking capacity) of treatment with laronidase to a pregnant woman with mucopolysaccharidosis I (MPS I) appear to outweigh the unknown risks to the embryo and/or fetus. Therefore, if a woman requires this therapy, it should not be withheld because of pregnancy.

FETAL RISK SUMMARY

Laronidase, a polymorphic variant of the human enzyme, α-L-iduronidase, is a glycoprotein prepared by recombinant DNA technology. It is indicated for patients with the Hurler and Hurler-Scheie forms of MPS I and for patients with the Scheie form who have moderate-to-severe symptoms. The predicted amino acid sequence of laronidase is identical to the polymorphic form of human α-L-iduronidase. Laronidase is given as a once-weekly 3–4 hour IV infusion. The mean elimination half-life ranges from 1.5 to 3.6 hours (1).

Hypersensitivity reactions, including anaphylaxis, may occur during laronidase IV infusions. Patients should receive antipyretics and/or antihistamines 60 minutes before the infusion. Hypotension was observed in 9% (2/22) of the patients receiving an infusion of laronidase in a placebo-controlled study (1). This adverse effect in a pregnant woman could have deleterious effects on placental perfusion, resulting in embryo and fetal harm.

Reproduction studies have been conducted in rats. No evidence of fetal harm was observed with a dose that was 6.2 times the human dose (assumed to be based on body weight). In addition, the same dose had no effect on male and female rat fertility (1).

It is not known if laronidase crosses the human placenta. The molecular weight is high (about 83,000), suggesting that the glycoprotein will not cross to the embryo or fetus.

A 2006 case report described a 21-year-old woman with MPS I, who became pregnant while receiving weekly infusions (100 U/kg) of laronidase (2). Exposure appears to have been no longer than 4 weeks. Further laronidase treatment was stopped. The woman went into spontaneous premature labor at 29 weeks’ gestation and delivered a healthy, normal 1250-g female infant. Although the cause of the preterm labor was unknown, the authors speculated that it might have been secondary to the disease (2).

BREASTFEEDING SUMMARY

No reports describing the use of laronidase during human lactation have been located.

The high molecular weight (about 83,000) suggests that the glycoprotein will not be excreted into breast milk. However, many proteins (e.g., immunoglobulins) are excreted into milk and absorbed by the infant in the first few days after birth. Thus, laronidase could potentially be excreted and absorbed.

If laronidase is excreted into milk, one strategy to reduce the exposure of a nursing infant, especially during the first week after birth, involves using the pharmacokinetics and dosing schedule of the drug. Laronidase has a short elimination half-life (1.5–3.6 hours) and is infused once weekly over 3–4 hours. The woman could nurse immediately before the start of the infusion, and then pump and dump her milk for about 8–12 hours after the end of the infusion. During this period, the infant could be fed breast milk stored earlier. This strategy should markedly reduce laronidase exposure of the nursing infant. Nevertheless, if a woman receiving laronidase therapy chooses to nurse, especially during the first week after birth, her infant should be closely monitored for the adverse effects most commonly observed in adults (skin rash, upper respiratory tract infection, hyperreflexia, paresthesia, chest pain, edema, and hypotension).

References

1.Product information. Aldurazyme. Genentech, 2007.

2.Anbu AT, Mercer J, Wraith JE. Effect of discontinuing of laronidase in a patient with mucopolysaccharidosis type 1. J Inherit Metab Dis 2006;29:230–1.