Sulfamethoxazole / trimethoprim Pregnancy and Breastfeeding Warnings

Sulfamethoxazole / trimethoprim is also known as: Bactrim, Bactrim DS, Bactrim IV, Bactrim Pediatric, Bethaprim, Bethaprim Pediatric, Co-trimoxazole, Cotrim, Cotrim DS, Cotrim Pediatric, SMZ-TMP DS, Septra, Septra DS, Septra IV, Sulfatrim, Sulfatrim Pediatric, Uroplus, Uroplus DS

Sulfamethoxazole / trimethoprim Pregnancy Warnings

Like all sulfonamides, sulfamethoxazole 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 demonstrating 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 to sulfonamides during the first and second trimesters compared to matched controls. Significance was found only when other defects were present. Third, the Michigan Medicaid surveillance study demonstrated possible teratogenic effects associated with trimethoprim-sulfamethoxazole (TMP-SMX). 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 and concomitant drug therapy are unaccounted for. Moreover, the individual contributions of TMP versus SMX are not known. 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. There has been a single report of Niikawa-Kuroki syndrome, characterized by mental and growth retardation and craniofacial abnormalities, associated with TMP-SMX. In summary, some experts, including Briggs, agree that in general, sulfonamides as single agents do not appear to pose a significant teratogenic risk. However, due to potential toxicity to the neonate, they should be avoided near term. There are no reports of teratogenicity associated with trimethoprim when used alone, but consideration of the Michigan Medicaid surveillance study is appropriate prior to using this drug during pregnancy.

Trimethoprim-sulfamethoxazole has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of fetotoxicity and teratogenicity. There are no controlled data in human pregnancy. Trimethoprim-sulfamethoxazole should only be given during pregnancy when benefit outweighs risk. Experts generally recommend that it be avoided near term due to the risk of kernicterus, hyperbilirubinemia, and jaundice.

Sulfamethoxazole / trimethoprim Breastfeeding Warnings

The average milk levels obtained after trimethoprim 160 mg twice a day range from 1.8 to 2 mcg/mL between two and three hours after dosing. No adverse effects of trimethoprim on nursing infants have been reported.

Trimethoprim and sulfamethoxazole are excreted into human milk. The manufacturer considers the use of trimethoprim-sulfamethoxazole to be contraindicated in breast-feeding women. The American Academy of Pediatrics considers the drug compatible with breast-feeding if the infant is healthy and full-term. Breast-feeding should be avoided if the infant is premature, ill, hyperbilirubinemic, or G6PD-deficient. 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 nursing based on the importance of the drug to the mother.

See Also...

• sulfamethoxazole/trimethoprim Consumer Information
• Pregnancy Support Group
• FDA Pregnancy Categories
• Medicine use during Pregnancy
• Medicine use while Breastfeeding
• Safe Medications during Breastfeeding

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