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
Animal studies have revealed evidence of fetotoxicity and teratogenicity. There are no controlled data in human pregnancy. Both drugs pass the placental barrier. The outcome of 186 pregnancies, during which the mother received either placebo or TMP-SMX, was reported in a retrospective study. The incidence of congenital abnormalities was 4.5% with placebo and 3.3% with TMP-SMX. No abnormalities were reported in the 10 children whose mothers used TMP-SMX during the first trimester. In a separate survey, no congenital abnormalities were found in 35 children whose mothers used oral TMP-SMX at time of conception or shortly thereafter. Some retrospective epidemiologic studies suggest first trimester exposure to TMP-SMX may be associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot. However, these studies had the following limitations: small number of exposed cases; lack of adjustment for multiple statistical comparisons and confounders; recall, selection, and information biases; and limited ability to generalize results. Additionally, outcome measures varied between studies, limiting cross-study comparisons. Alternatively, statistically significant links between TMP-SMX exposure and specific malformations were not detected by other epidemiologic studies. Like all sulfonamides, sulfamethoxazole crosses the placenta, reaching equilibrium with maternal serum within 2 to 3 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). Experts generally recommend that TMP-SMX be avoided near term due to the risk of kernicterus, hyperbilirubinemia, and jaundice. While there are no definitive data demonstrating an association between sulfonamides and congenital defects, 4 significant sources of information are worthy of mention. First, a retrospective study of 1369 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 TMP-SMX. This report is a summary of information from 2 studies, one in which 1116 of 104,000 pregnant women from 1980 to 1983, and one in which 2296 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 3 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, 1455 of which had first trimester exposure to sulfonamides. In addition, a total of 5689 exposures to sulfonamides at any time 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. FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
FDA pregnancy category: D Trimethoprim-sulfamethoxazole (TMP-SMX) should be used during pregnancy only if the benefit outweighs the risk. Comments: TMP-SMX may interfere with folic acid metabolism.
Sulfamethoxazole / trimethoprim Breastfeeding Warnings
Sulfamethoxazole-trimethoprim levels in breast milk are about 2% to 5% of the recommended daily dose for infants over 2 months of age. The average milk levels obtained after trimethoprim 160 mg twice a day range from 1.8 to 2 mcg/mL between 2 and 3 hours after dosing. No adverse effects of trimethoprim on nursing infants have been reported.
Caution is recommended, especially if the infant is premature, ill, jaundiced, or stressed (risk of bilirubin displacement and kernicterus); sulfamethoxazole-trimethoprim is contraindicated in patients younger than 2 months. Excreted into human milk: Yes (sulfamethoxazole and trimethoprim) Excreted into animal milk: Data not available Sulfamethoxazole-trimethoprim is considered compatible with breastfeeding by the American Academy of Pediatrics if the infant is healthy and full-term. Sulfamethoxazole-trimethoprim has been used without apparent harmful effects in the nursing infant.
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