Polymyxin-B-trimethoprim ophthalmic solution has been assigned to pregnancy category C by the FDA. Animal studies with polymyxin-B have not been reported. Animal studies have revealed evidence of teratogenicity associated with the systemic use of trimethoprim. In some animal studies, increased fetal loss was associated with the use of orally administered trimethoprim in doses 6 times the human therapeutic dose. Retrospective data regarding the use of trimethoprim in combination with sulfamethoxazole in humans have revealed a possible association with congenital abnormalities. Trimethoprim may interfere with folic acid metabolism. Polymyxin B and trimethoprim undergo minimal absorption after ophthalmic administration (1 unit/mL and 0.03 mcg/mL, respectively). Polymyxin-B-trimethoprim ophthalmic solution is only recommended for use during pregnancy when benefit outweighs risk.

There are no reports of teratogenicity associated with trimethoprim as a single agent. However, the Michigan Medicaid surveillance study demonstrated possible teratogenic effects associated with the combination drug, trimethoprim-sulfamethoxazole (TMP-SMX) (Written communication, Franz Rosa, MD, Food and Drug Administration, 1994). 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.

Another retrospective study has reported on the outcome of 186 pregnancies during which the mother received either placebo or oral TMP-SMX. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those who received TMP-SMX. There were no abnormalities in the 10 children whose mothers received TMP-SMX during the first trimester. In a separate survey, the authors of this study found no congenital abnormalities in 35 children whose mothers had received oral TMP-SMX at the time of conception or shortly thereafter.

There has also been a single report of Niikawa-Kuroki syndrome, characterized by mental and growth retardation and craniofacial abnormalities, associated with TMP-SMX.

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There are no data on the excretion of polymyxin B-trimethoprim ophthalmic solution into human milk. Polymyxin B and trimethoprim undergo minimal systemic absorption after ophthalmic administration (1 unit/mL and 0.03 mcg/mL, respectively). The manufacturer recommends that caution be used when administering polymyxin B-trimethoprim ophthalmic to nursing women.

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