Sulfisoxazole Pregnancy and Breastfeeding Warnings

Brand names: Gantrisin, Gantrisin Pediatric, Truxazole

Sulfisoxazole Pregnancy Warnings

Sulfisoxazole has been assigned to pregnancy category C by the FDA. Some animal studies have revealed evidence of teratogenicity. There are no controlled data in human pregnancies. Sulfisoxazole should only be given during pregnancy when benefit outweighs risk. Sulfisoxazole use near term is considered contraindicated.

Like all sulfonamides, sulfisoxazole crosses the placenta, reaching equilibrium with maternal serum within two to three hours after administration. Because sulfonamides compete with bilirubin for binding to serum albumin, free bilirubin levels rise in the presence of sulfonamides. Neonates are, therefore, at risk of hyperbilirubinemia, jaundice, and kernicterus when sulfonamides are administered to the mother near term (prior to birth, the fetus is able to dispose of bilirubin via the placental circulation).

While there are no definitive data to demonstrate an association between sulfonamides and congenital defects, four significant sources of information are worthy of mention.

First, a retrospective study of 1,369 patients revealed that significantly more mothers of 458 offspring with congenital malformations had taken sulfonamides than did mothers of normal offspring.

Second, a retrospective study of 599 offspring with oral clefts revealed a significantly greater exposure of sulfonamides during the first and second trimesters compared with matched controls. Significance was found only when other defects were present.

Third, the Michigan Medicaid surveillance study showed a possible association between the combination drug, trimethoprim-sulfamethoxazole (TMP-SMX), and congenital defects (written communication. This report is a summary of information from two studies, one in which 1,116 of 104,000 pregnant women from 1980 to 1983, and one in which 2,296 of 229,000 pregnant women from 1985 to 1992 received TMP-SMX. In the first study 83 total defects (13 cardiovascular defects) were observed (14 and 2 were expected, respectively). In the second study, 126 total defects (37 cardiovascular defects) were observed (98 and 27 were expected, respectively). Cleft palate was observed in three cases in the latter study. These data support an association between TMP-SMX and congenital defects, although other causes, such as the underlying disease(s) of the mother, the contribution of trimethoprim, and concomitant drug therapy are unaccounted for.

Fourth, and finally, the Collaborative Perinatal Project monitored 50,282 mother-child pairs, 1,455 of which had first trimester exposure to sulfonamides. In addition, a total of 5,689 exposures to sulfonamides at anytime during pregnancy were retrospectively analyzed. There was no evidence to suggest a relationship of sulfonamides to large categories of major or minor malformations.

In summary, some experts, including Briggs, agree that in general sulfonamides as single agents do not appear to pose a significant teratogenic risk, but due to their potential toxicity to the neonate, they should be avoided near term.

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Sulfisoxazole Breastfeeding Warnings

Sulfisoxazole is excreted into human milk in low concentrations. The manufacturer considers the use of sulfisoxazole to be contraindicated in breast-feeding women. It is considered compatible with breast-feeding by the American Academy of Pediatrics if the infant is healthy and full-term. Breast-feeding should be avoided if the infant is premature, is ill, has hyperbilirubinemia, or has glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because sulfonamides may cause kernicterus in infants less than 2 months of age, a decision should be made to discontinue (or substitute) drug therapy or discontinue breast-feeding based on the importance of the drug to the mother.

Because sulfisoxazole is relatively water-soluble, its concentration in milk is low. The average milk to maternal drug level ratio is 0.06. In one study, the total amount of sulfisoxazole recovered in milk 48 hours after a 4-gram divided dose was equivalent to only 0.45%. These data indicate that sulfisoxazole poses a very small risk to the nursing infant.

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Further information

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