SULFAMETHOXAZOLE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Displaces dihydropteroate synthetase from its substrate para-aminobenzoic acid (PABA), inhibiting bacterial folate synthesis. Bacteriostatic against susceptible organisms.
| Metabolism | Primarily metabolized in the liver via N-acetylation by N-acetyltransferase 2 (NAT2) and glucuronidation. Minor metabolism via CYP450. |
| Excretion | Primarily renal; ~80-90% excreted unchanged in urine, with 15-30% as acetylated metabolite. Biliary/fecal <5%. |
| Half-life | 9-11 hours in adults with normal renal function. Prolonged in renal impairment: up to 20-30 hours. In neonates, 6-12 hours. |
| Protein binding | ~65-70% bound, primarily to albumin. |
| Volume of Distribution | 0.15-0.3 L/kg (approx 10-20 L in adults), reflecting distribution primarily into extracellular fluid. |
| Bioavailability | Oral: ~85-100% (well absorbed); no significant first-pass metabolism. |
| Onset of Action | Oral: 2-4 hours for peak bacteriostatic effect; IV: immediate systemic exposure, bacteriostatic action within 1-2 hours. |
| Duration of Action | Approximately 12 hours following oral or IV administration, supporting twice-daily dosing. Sustained above MIC for 8-12 hours. |
800 mg sulfamethoxazole with 160 mg trimethoprim (DS tablet) orally every 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: 50% dose every 24 hours; CrCl <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: avoid use due to risk of toxicity. |
| Pediatric use | 8 mg/kg sulfamethoxazole (with 1.6 mg/kg trimethoprim) orally every 12 hours; up to 1600 mg sulfamethoxazole per dose. |
| Geriatric use | Adjust based on renal function; monitor for hypoglycemia, hyperkalemia, and folate deficiency; avoid in combination with ACE inhibitors and ARBs. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
May potentiate the effects of warfarin and sulfonylureas Can cause Stevens-Johnson syndrome and blood dyscrasias.
| Breastfeeding | Compatible with caution; low levels in breast milk (M/P ratio ~0.2-0.3). Potential risk of kernicterus in premature or hyperbilirubinemic neonates; monitor infant for jaundice. |
| Teratogenic Risk | First trimester: Associated with increased risk of neural tube defects, cardiovascular anomalies, and cleft palate due to folate antagonism. Second/third trimester: Risk of kernicterus in neonates if used near term due to bilirubin displacement; avoid after 32 weeks gestation. |
■ FDA Black Box Warning
Fatalities have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Use in pregnancy at term or in nursing mothers may cause kernicterus.
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to sulfonamides or any component. Patients with marked hepatic damage or severe renal insufficiency. Use in pregnancy at term and during lactation (risk of kernicterus). Infants less than 2 months of age (except for treatment of congenital toxoplasmosis).
| Precautions | Do not administer to patients with hypersensitivity to sulfonamides. Avoid use in patients with severe renal or hepatic impairment. Monitor for skin rashes, fever, pallor, or other signs of serious adverse reactions. Caution in patients with folate deficiency, G6PD deficiency, or porphyria. May cause photosensitivity. |
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| Fetal Monitoring |
| Maternal: CBC with differential, renal function, liver function tests. Fetal: Ultrasound for structural anomalies if used first trimester; bilirubin monitoring in neonate if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported in humans; theoretical risk of folate antagonism impairing implantation. |