Immunologic Agent (Antirheumatic)
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 auranofin in human pregnancy have been located. Although there was evidence of embryo–fetal toxicity and/or teratogenicity in animals, the doses used caused maternal toxicity and the comparisons to the human dose (HD) were based on body weight. Doses that were not maternally toxic did not cause these effects. Based on experience with other gold compounds (see Gold Sodium Thiomalate), gold does not appear to pose a major risk to the fetus. However, long-term follow-up studies of exposed fetuses have not been reported. If auranofin is indicated in a pregnant woman she should be informed of this information.
FETAL RISK SUMMARY
Auranofin is an oral disease-modifying antirheumatic drug (DMARD) containing 29% gold. It is indicated in the management of adults with active classical or definite rheumatoid arthritis who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of full dose of one or more nonsteroidal anti-inflammatory drugs. Auranofin is rapidly metabolized and intact auranofin is undetectable in blood. Approximately 25% of the gold in auranofin is absorbed. The gold in auranofin is moderately bound (60%) to plasma proteins. The mean terminal plasma half-life of auranofin gold at steady state is 26 days (range 21–31 days), whereas the mean terminal body half-life at steady state is 80 days (range 42–128 days) (1).
Reproduction studies have been conducted in rabbits, rats, and mice. In rabbits, maternal toxic (impaired food intake) doses about 4–50 times the HD resulted in decreased fetal weights, increased incidence or resorptions and abortions, and an increased incidence of congenital abnormalities, mainly abdominal defects such as gastroschisis and umbilical hernia. No teratogenicity was noted in rats given a maternal toxic dose 42 times the HD, but there was an increase in the incidence of resorptions and a decrease in litter size and weight. A dose 21 times the HD that was not maternally toxic did not cause these effects or teratogenicity. In mice, a dose 42 times the HD was not teratogenic or maternal toxic (1).
In a 24-month carcinogenicity study in rats, doses that were 3–21 times the HD resulted in renal tumors. In a 12-month study in rats, a dose 192 times the HD caused renal tumors, whereas a dose 30 times the HD did not. In an 18-month study in mice, doses that were 8–72 times the HD were not associated with a significant increase in tumors. Auranofin was mutagenic in one assay but not in other assays (1). The effects of the drug animal fertility were apparently not studied.
Intact auranofin is not available to cross to the embryo or fetus because the agent has not been detected in blood. However, gold, released from auranofin, will cross the placenta (see Gold Sodium Thiomalate).
BREASTFEEDING SUMMARY
No reports describing the use of auranofin during human lactation have been located. Intact auranofin has not been detected in blood and, thus, would not be excreted into breast milk. However, gold, released from auranofin, will be excreted into milk (see Gold Sodium Thiomalate). Based solely on that information, breastfeeding when the mother is being treated with auranofin is probably compatible.
Reference
1.Product information. Ridaura. Prometheus Laboratories, 2007.