GOLD SODIUM THIOMALATE

Fetal Risk Summary

Gold sodium thiomalate is indicated in the treatment of active rheumatoid arthritis. Teratogenic effects were observed in rats and rabbits given SC doses 140 and 175 times the usual human dose, respectively, during organogenesis (1). In rats, the defects were hydrocephaly and microphthalmia, whereas those in rabbits were limb malformations and gastroschisis.

Gold compounds have been used for the treatment of maternal rheumatoid arthritis and other conditions in a small number of pregnancies (2,3,4,5,6 and 7). One review noted that several pregnant patients had been treated with gold salts without harmful effects observed in the newborns (2). In a Japanese report, 119 patients were treated during the 1st trimester with gold, 26 of whom received the drug throughout pregnancy (3). Two anomalies were observed in the newborns—a dislocated hip in one infant and a flattened acetabulum in another—but the association with the therapy is unknown. A German case history involved a woman who received her last injection of gold for chronic polyarthritis in the 3rd week of pregnancy (4). A growth-retarded, 1750-g female infant was delivered at 40 weeks' gestation. Other than the low birth weight, no other abnormalities were noted in the infant, whose development during the next 2 years was normal. In another case, a woman had been treated with gold sodium thiomalate (sodium aurothiomalate) for 2 years immediately prior to pregnancy, receiving her last dose when several weeks pregnant (5). No adverse effects in the newborn were mentioned.

Gold compounds cross the placenta. A patient who had received a total dose of 570 mg of gold sodium thiomalate from before conception through the 20th week of gestation elected to terminate her pregnancy (6). No obvious fetal abnormalities were observed, but gold deposits were found in the fetal liver and kidneys. A second patient received monthly 100-mg injections of gold throughout pregnancy (7). The last dose, given 3 days prior to delivery, produced a cord serum concentration of 2.25 µg/mL, 57% of the simultaneous maternal serum level. No anomalies were observed in the infant.

Although gold compounds apparently do not pose a major risk to the fetus, the clinical experience is limited and long-term follow-up studies of exposed fetuses have not been reported.

Breast Feeding Summary

Gold is excreted in milk (5,8,9 and 10). A woman received a total aurothioglucose dose of 135 mg in the postpartum period (8). Gold levels in two milk samples collected a week apart were 8.64 and 9.97 µg/mL. The validity of these figures has been challenged on a mathematical basis, so the exact amount excreted is open to question (9). In addition, the timing of the samples in relation to the dose was not given. Of interest, however, was the demonstration of gold levels in the infant's red blood cells (0.354 µg/mL) and serum (0.712 µg/mL) obtained on the same date as the second milk sample. The author speculated that this unexpected oral absorption may have been the cause of various unexplained adverse reactions noted in nursing infants of mothers receiving gold injections, such as rashes, nephritis, hepatitis, and hematologic abnormalities (8).

Another report described a lactating woman who was treated with 50 mg of gold sodium thiomalate weekly for 7 weeks after an initial 20-mg dose (total dose 370 mg) (10). Milk and infant urine samples collected 66 hours after the last dose yielded gold levels of 22 and 0.4 ng/mL, respectively. Repeat samples collected 7 days after an additional 25-mg dose produced milk and urine levels of 40 and <0.4 ng/mL, respectively. Three months after cessation of therapy, transient facial edema was observed in the nursing infant, but it was not known whether this was related to the maternal gold administration.

In a 1986 report, two women were given IM injections of gold sodium thiomalate (5). One patient received 20 mg on day 1 followed by 50 mg on day 3. Milk concentrations rose from a low of 17 ng/mL (1.4% of simultaneous maternal serum) 10 hours after the first dose to a peak of 153 ng/mL (approximately 4.6% of maternal serum) 22 hours after the second dose. The second patient received three doses of the gold salt consisting of 10 mg on day 1, 20 mg on day 8, and 20 mg on day 12. The peak milk concentration, 185 ng/mL (10.4% of maternal serum), occurred 3 hours after the third dose. The levels of gold in the milk of both patients increased steadily over the sampling periods. The investigators estimated that the nursing infant would receive about 20% of the maternal dose (5).

In summary, three studies have described the excretion of gold into breast milk with milk concentrations, in two of the studies, similar in magnitude. Gold absorption by the nursing infant has been documented. Although adverse effects have been suggested, a direct cause and effect relationship has not been proven. At least one set of investigators cautioned that, due to the prolonged maternal elimination time after gold administration and the potential for toxicity in the infant, nursing should be avoided (5). However, the American Academy of Pediatrics considers gold salts to be compatible with breast feeding (11).

References

1. Product information. Myochrysine. Merck, 2000.
2. Freyberg RH, Ziff M, Baum J. Gold therapy for rheumatoid arthritis. In Hollander JL, McCarty DJ Jr, eds. Arthritis and Allied Conditions. 8th ed. Philadelphia, PA:Lea & Febiger, 1972:479.
3. Miyamoto T, Miyaji S, Horiuchi Y, Hara M, Ishihara K. Gold therapy in bronchial asthma-special emphasis upon blood level of gold and its teratogenicity. J Jpn Soc Intern Med 1974;63:1190–7.
4. Fuchs U, Lippert TH. Gold therapy and pregnancy. Dtsch Med Wochenschr 1986;111:31–4.
5. Ostensen M, Skavdal K, Myklebust G, Tomassen Y, Aarbakke J. Excretion of gold into human breast milk. Eur J Clin Pharmacol 1986;31:251–2.
6. Rocker I, Henderson WJ. Transfer of gold from mother to fetus. Lancet 1976;2:1246.
7. Cohen DL, Orzel J, Taylor A. Infants of mothers receiving gold therapy. Arthritis Rheum 1981;24:104–5.
8. Blau SP. Metabolism of gold during lactation. Arthritis Rheum 1973;16:777–8.
9. Gottlieb NL. Suggested errata. Arthritis Rheum 1974;17:1057.
10. Bell RAF, Dale IM. Gold secretion in maternal milk. Arthritis Rheum 1976;19:1374.
11. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.