Antigout (Uricosuric)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of pegloticase in human pregnancy have been located. Although animal data suggest low risk, the absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. If the drug is used in a pregnancy, the woman should be informed of the lack of data.
FETAL RISK SUMMARY
Pegloticase is a PEGylated, recombinant, mammalian urate oxidase enzyme given as an IV infusion every 2 weeks. It is indicated for the treatment of chronic gout in adult patients who are refractory to conventional therapy. No information was provided by the manufacturer on plasma protein binding, metabolism, or elimination half-life (1). However, in two studies, the mean elimination half-life was 12.5 (range 3.5–21.5 days) and 14 days (range 7–44 days) (2,3).
Reproduction studies have been conducted in rats. In this species, doses given on gestation days 6–16 that were 6–50 times higher than the maximum recommended human dose based on BSA were not teratogenic (1).
Pegloticase has not been evaluated for carcinogenesis, mutagenesis, or impairment of fertility.
It is not known if pegloticase crosses the human placenta. The high molecular weight (about 540,000) suggests that exposure of the embryo–fetus is unlikely to occur.
BREASTFEEDING SUMMARY
No reports describing the use of pegloticase during human lactation have been located.
The high molecular weight (about 540,000) suggests that the enzyme will not be excreted into breast milk. If excretion does occur, the enzyme most likely would be digested in the infant’s gut. Consequently, although the risk to a nursing infant is unknown, it appears to be negligible.
References
1.Product information. Krystexxa. Savient Pharmaceuticals, 2010.
2.Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, Hershfield MS. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis Rheum 2007;56:1021–8.
3.Yue CS, Huang W, Alton M, Maroli AN, Wright D, Marco MD. Population pharmacokinetic and pharmacodynamic analysis of pegloticase in subjects with hyperuricemia and treatment-failure gout. J Clin Pharmacol. 2008;48:708–18.