Risk Factor: C
Class: Cardiovascular drugs / Cardiac drugs

Contents of this page:

Fetal Risk Summary

No reports linking digitalis or the various digitalis glycosides with congenital defects have been located. Animal studies have failed to show a teratogenic effect (1).

Rapid passage to the fetus has been observed after digoxin and digitoxin (2,3,4,5,6,7,8 and 9). One group of investigators found that the amount of digitoxin recovered from the fetus was dependent on the length of gestation (2). In the late 1st trimester, only 0.05%0.10% of the injected dose was recovered from three fetuses. Digitoxin metabolites accounted for 0.18%0.33%. At 34 weeks of gestation, digitoxin recovery was 0.85% and metabolite recovery was 3.49% from one fetus. Average cord concentrations of digoxin in three reports were 50%, 81%, and 83% of the maternal serum (3,4,9). The highest fetal concentrations of digoxin in the second half of pregnancy were found in the heart (5). The fetal heart has only a limited binding capacity for digoxin in the first half of pregnancy (5). In animals, amniotic fluid acts as a reservoir for digoxin, but no data are available in humans after prolonged treatment (5). The pharmacokinetics of digoxin in pregnant women have been reported (10,11).

Digoxin has been used for both maternal and fetal indications (e.g., congestive heart failure and supraventricular tachycardia) during all stages of gestation without causing fetal harm (12,13,14,15,16,17,18,19,20,21,22,23,24 and 25). Direct administration of digoxin to the fetus by periodic IM injections has been used to treat supraventricular tachycardia when indirect therapy via the mother failed to control the arrhythmia (26).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 34 newborns had been exposed to digoxin during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (2.9%) major birth defect was observed (one expected), an oral cleft. Although the number of exposures is small, these data are supportive of previous experience for a lack of association between the drug and congenital defects.

Fetal toxicity resulting in neonatal death has been reported after maternal overdose (27). The mother, in her 8th month of pregnancy, took an estimated 8.9 mg of digitoxin as a single dose. Delivery occurred 4 days later. The baby demonstrated digitalis cardiac effects until death at age 3 days from prolonged intrauterine anoxia.

In a series of 22 multiparous patients maintained on digitalis, spontaneous labor occurred more than 1 week earlier than in 64 matched controls (28). The first stage of labor in the treated patients averaged 4.3 hours vs. 8 hours in the control group. In contrast, others found no effect on duration of pregnancy or labor in 122 patients with heart disease (29).

Breast Feeding Summary

Digoxin is excreted into breast milk. Data for other cardiac glycosides have not been located. Digoxin milk:plasma ratios have varied from 0.60.9 (4,7,30,31). Although these amounts seem high, they represent very small amounts of digoxin due to significant maternal protein binding. No adverse effects in the nursing infant have been reported. The American Academy of Pediatrics considers digoxin to be compatible with breast feeding (32).


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