Clinical safety rating: caution
TMP-SMX (Co-trimoxazole) is a folate antagonist with trimester-dependent risks. Trimethoprim inhibits dihydrofolate reductase, potentially impairing folate metabolism in early embryogenesis — associated with NTDs and cardiovascular defects in some studies. Sulfamethoxazole at term can displace bilirubin from albumin causing neonatal jaundice and theoretical kernicterus risk. Despite this, it remains essential for treating Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii, and certain MDR UTIs. Supplementation with folic acid 5 mg/day is recommended if used in T1.
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Dosing varies by indication and patient profile. Always follow your institution's current prescribing guidelines.
| Renal impairment | Consult protocols for adjustment. |
| Liver impairment | Consult protocols for adjustment. |
| 1st trimester | Caution. Folate antagonism may increase risk of NTDs and cardiac defects. Use folic acid 5 mg/day. Use only if no alternatives. |
| 2nd trimester | Caution. Acceptable for infections where no safer alternative exists. |
| 3rd trimester | Avoid at term (last 4 weeks). Risk of neonatal hyperbilirubinemia and theoretical kernicterus from bilirubin displacement by sulfonamide. |
Clinical note
TMP-SMX (Co-trimoxazole) is a folate antagonist with trimester-dependent risks. Trimethoprim inhibits dihydrofolate reductase, potentially impairing folate metabolism in early embryogenesis — associated with NTDs and cardiovascular defects in some studies. Sulfamethoxazole at term can displace bilirubin from albumin causing neonatal jaundice and theoretical kernicterus risk. Despite this, it remains essential for treating Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii, and certain MDR UTIs. Supplementation with folic acid 5 mg/day is recommended if used in T1.
| Breastfeeding | Caution. Compatible in most circumstances; avoid in neonates with jaundice or G6PD deficiency. Monitor infant. |
Avoid in patients with known hypersensitivity to this drug or any of its components.
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