Endocrine/Metabolic Agent (Gaucher’s Disease)
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
No imiglucerase-related adverse effects in embryos and fetuses have been reported in the limited data on pregnancies complicated by type I Gaucher’s disease. Pregnancy may exacerbate existing disease or result in new disease manifestations, but the data suggest that treatment may reduce the risk of spontaneous abortion and bleeding complications. However, systematic human or animal studies have not been conducted. Nevertheless, a brief 2009 review cited a recommendation from the European Medicines Agency that in women receiving imiglucerase, treatment continuation throughout pregnancy should be considered (1).
FETAL RISK SUMMARY
Imiglucerase, an enzyme given by IV infusion, is used in the treatment of patients with type I Gaucher’s disease. It is in the same pharmacologic subclass as alglucerase, taliglucerase alfa, and velaglucerase alfa. Imiglucerase replaces the endogenous enzyme β-glucocerebrosidase. Imiglucerase is produced by recombinant DNA technology and differs from the endogenous enzyme by one amino acid substitution. After infusion, the terminal elimination half-life is 3.6–10.4 minutes (2).
Reproduction studies with imiglucerase have apparently not been conducted. Moreover, the carcinogenic and mutagenic potential of imiglucerase has not been studied.
It is not known if imiglucerase crosses the human placenta. The relatively high molecular weight (about 55,600) and the short terminal half-life suggest that placental transfer will be limited.
A 2007 case report described the pregnancy outcome of a 23-year-old woman with Gaucher’s disease who was treated throughout gestation with imiglucerase 30 U/kg every 2 weeks (3). She gave birth to a healthy female infant at term (additional details not provided).
Outcomes of exposed pregnancies treated with either imiglucerase or the similar enzyme, alglucerase, have been summarized from surveys gathered from international treatment centers, from reports in the literature, as well as from the manufacturer’s pharmacovigilance database. The total number of exposed patients is unclear as there could be overlap between the various sources of reports. However, as reviewed in a 2010 publication, among 43 to 78 treated pregnancies compared with 71 to 388 untreated pregnancies with the same disease, the risk of spontaneous abortion, disease-related bleeding complications at delivery, and disease-related complications postpartum were reduced. No evidence of teratogenic risk was noted (4,5). An additional four case reports (which may or may not have been included in the larger review) described successful pregnancy outcome in patients treated with imiglucerase, including three healthy liveborn singletons and one set of healthy liveborn twins (6–8).
BREASTFEEDING SUMMARY
Although the relatively high molecular weight (about 55,600) and the short terminal elimination half-life (3.6–10.4 minutes) suggest that excretion of the enzyme in milk will be limited, one case report did detect imiglucerase. Samples were collected from maternal serum and breast milk before and up to 24 hours after an imiglucerase IV infusion (8). Slightly increased enzymatic activity was observed in the first breast milk sample after the infusion, but levels were undetectable thereafter.
In a 2007 case report discussed earlier, a 23-year-old woman took imiglucerase 30 U/kg every 2 weeks throughout pregnancy and during the first 3 months of breastfeeding (3). Because of Gaucher’s disease progression, her dose was increased to 60 U/kg every 2 weeks. She continued this dose until breastfeeding was discontinued at 1 year. Apparently, no toxicity was noted in the infant, but the infant’s condition was not mentioned (3).
The effect, if any, on a nursing infant is unknown. However, the enzyme is probably digested in the infant’s gut and is unlikely to reach the systemic circulation (1).
References
1.Belmatoug N. Considerations for pregnant patients with Gaucher disease: challenges for the patient and physician. Clin Ther 2009;31(Suppl C): S192–3.
2.Product information. Cerezyme. Genzyme, 2011.
3.Mrsic M, Fumic K, Vrcic H, Potocki K, Stern-Padovan R, Prutki M, Durakoviae N. Successful pregnancy on enzyme replacement therapy with Cerezyme. Clin Ther 2007;29(Suppl C):S84.
4.Zimran A, Morris E, Mengel E, Kaplan P, Belmatoug N, Hughes DA, Malinova V, Heitner R, Sobreira E, Mrsic M, Granovsky-Frisaru S, Amato D, vom Dahl S. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis 2009;43:264–88.
5.Granovsky-Grisaru S, Belmatoug N, vom Dahl S, Mengel E, Morris E, Zimran A. The management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol 2011;156:3–8.
6.Sherer Y, Dulitzki M, Levy Y, Livneh A, Shoenfeld Y, Langevitz P. Successful pregnancy outcome in a patient with Gaucher’s disease and antiphospholipid syndrome. Ann Hematol 2002;81:161–3.
7.Malinova V, Poupetova H, Dvorakova L, Zeman J. Enzyme replacement therapy for Gaucher disease in twin pregnancy. Int J Gynaecol Obstet 2009; 106:64–6.
8.Sekijima Y, Ohashi T, Ohira S, Kosho T, Fukushima Y. Successful pregnancy and lactation outcome in a patient with Gaucher disease receiving enzyme replacement therapy, and the subsequent distribution and excretion of imiglucerase in human breast milk. Clin Ther 2010;32:2048–52.