Antidote
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
Although the limited animal data suggest low embryo–fetal risk, there are no reports of dimercaprol use during organogenesis in humans. This absence of data prevents an assessment of the human embryo risk. However, the maternal benefit, and indirect embryo–fetal benefit, appears to far outweigh the unknown embryo–fetal risk. Therefore, if indicated, dimercaprol should not be withheld because of pregnancy (1).
FETAL RISK SUMMARY
Dimercaprol is a chelating agent indicated in the treatment of arsenic, gold, and acute mercury poisoning, and for lead poisoning when used concomitantly with edetate calcium disodium. It is not very effective for chronic mercury poisoning. Dimercaprol is administered by IM injection. The mechanism of action involves dimercaprol sulfhydryl groups forming complexes with certain heavy metals, thereby preventing or reversing the metal from binding sulfhydryl-containing enzymes (2).
A 1998 review cited five studies that evaluated the reproductive toxicity of dimercaprol in animals (3). The antidote was given to pregnant mice in doses of 15–60 mg/kg/day for 4 days to protect against methylmercury-induced developmental toxicity. Similar single or multiple doses given to mice daily did not alleviate arsenate-induced fetal toxicity, but no dimercaprol-induced developmental toxicity was noted. In another study, SC dimercaprol (125 mg/kg/day) in mice on gestational days 9–12 resulted in embryotoxicity (growth restriction, increased mortality) and teratogenicity (digits with abnormal direction and situation, cleft palate, and cerebral hernia) (3). (Note: the human IM dose, depending on the type of poisoning, varies from 2.5 mg/kg/day to 18 mg/kg/day with up to 13-day courses.)
It is not known if dimercaprol can cross the human placenta. The low molecular weight (about 124) suggests that the drug does cross to the embryo–fetal compartment.
The first reported case of dimercaprol in a human pregnancy appeared in 1948 (4). An 18-year-old woman at about 26 weeks’ gestation was given dimercaprol for arsenical encephalopathy. The woman had received several arsenic-containing injections for vaginal and perineal warts 10 days earlier. She was given a total dose of 5440 mg over 13 days. Labor was induced at about 36 weeks’ gestation because of eclampsia, and she delivered a 5.5-lb male infant who required resuscitation but was otherwise healthy. Long-term follow-up of the infant was not reported (4).
A 1969 case report detailed the pregnancy outcome of a 17-year-old patient at 30 weeks’ gestation who had ingested approximately 30 mL of arsenic trioxide containing 1.32% of total elemental arsenic (5). About 24 hours after ingestion, she was treated with 150 mg of IM dimercaprol but developed renal failure over the next 72 hours. Spontaneous labor occurred, and she delivered a 1.1-kg female infant with an Apgar score of 4 at 1 minute. A qualitative test for arsenic on the baby’s plasma was negative. The infant died 11 hours later of respiratory distress syndrome. At autopsy, toxicologic analysis for arsenic (reported as arsenic trioxide per 100 g of wet tissue) revealed that the metal had crossed the placenta to the fetus with the following concentrations: 0.740 mg (liver), 0.150 mg (kidneys), and 0.0218 mg (brain). The arsenic levels in the infant were all significantly higher than those measured in adult autopsy material. The authors could locate only one other similar case of inorganic arsenic poisoning in pregnancy. In that case, published in 1928 in a French journal, both the mother and infant died. Arsenic levels for the infant were not reported, but the level in the maternal liver was 0.56 g/100 g, less than the level found in the current infant (5).
A 2002 report described the use of IV edetate and IM dimercaprol (dose not specified) in a woman at 30 weeks’ gestation with a high blood lead concentration (5.2 µmol/L; goal ≤0.48 µmol/L) (6). Twenty-four hours after initiation of chelation therapy, her lead level was 2.3 µmol/L. Twelve hours later, labor was induced because of uterine hemorrhage and she gave birth to a 1.6-kg (75th percentile) female infant. Lead concentration in the cord blood was 7.6 µmol/L. The Apgar scores were 4 and 6 (presumably at 1 and 5 minutes, respectively). The newborn was flaccid with absent reflexes, no movement to noxious stimuli, and no gag reflex, but she did have spontaneous eye movement. Bilateral diaphragmatic palsy was confirmed by fluoroscopy. During her 7 months of hospitalization, the infant received multiple courses of chelation to treat the intrauterine lead intoxication. In spite of this therapy, she had right sensorineural deafness and neurodevelopment delay at discharge. Oral succimer was continued at home because the blood lead level was still elevated (0.95 µmol/L). The mother’s lead source was identified as herbal tablets that had been prescribed for a gastrointestinal complaint. She had taken the tablets periodically over the past 9 years and throughout her pregnancy. Mercury also was present in some of the tablets. The lead intake during pregnancy was estimated to be 50 times the average weekly intake of Western populations (6). In a 2003 case report and review of severe lead poisoning in pregnancy, seven new cases and eight from the literature were identified (7). Ten of the women admitted to intentional ingestion of pica. Among the 15 cases, five underwent chelation while they were pregnant, four with edetate calcium disodium, including one who also received IM dimercaprol, and one who received succimer. No lead-induced congenital defects were noted in the infants, but all received chelation therapy in the neonatal period (7).
BREASTFEEDING SUMMARY
No reports describing the use of dimercaprol during human lactation have been located. The molecular weight (about 124) and the typical prolonged therapy (13 days) suggest that the antidote will be excreted into breast milk. The effect, if any, of this exposure on a nursing infant is unknown. Because the use of dimercaprol implies poisoning with arsenic, gold, mercury, or lead, these metals also will be excreted into milk and are toxic to a nursing infant. Therefore, breastfeeding is contraindicated in women receiving dimercaprol.
References
1.Bailey B. Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women? Birth Def Res A Clin Mol Teratol 2003;67:133–40.
2.Product information. BAL in oil. Akorn, 2004.
3.Domingo JL. Developmental toxicity of metal chelating agents. Reprod Toxicol 1998;12:499–510.
4.Kantor HI, Levin PM. Arsenical encephalopathy in pregnancy with recovery. Am J Obstet Gynecol 1948;56:370–4.
5.Lugo G, Cassady G, Palmisano P. Acute maternal arsenic intoxication with neonatal death. Am J Dis Child 1969;117:328–30.
6.Tait PA, Vora A, James S, Fitzgerald DJ, Pester BA. Severe congenital lead poisoning in a preterm infant due to a herbal remedy. Med J Aust 2002;177:193–5.
7. Shannon M. Severe lead poisoning in pregnancy. Ambul Pediatr 2003;3:37-9.