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. |
| Molecular Weight | 253.28 |
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 | Contraindicated due to risk of neural tube defects and other congenital malformations; folate antagonist. |
| 2nd trimester | Use only if benefit outweighs risk; risk of kernicterus in newborn if used near term. |
| 3rd trimester | Avoid after 38 weeks due to risk of hemolytic anemia and kernicterus in the neonate. |
Clinical note
May potentiate the effects of warfarin and sulfonylureas Can cause Stevens-Johnson syndrome and blood dyscrasias.
| Placental transfer | Crosses placenta readily; fetal levels reach 50-100% of maternal serum levels. |
| Breastfeeding | Excreted into breast milk in small amounts; may cause kernicterus in jaundiced or G6PD-deficient infants; American Academy of Pediatrics considers compatible with breastfeeding but caution advised. |
■ 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 componentHistory of drug-induced immune thrombocytopenia with sulfonamidesPorphyriaMegaloblastic anemia due to folate deficiencySevere hepatic or renal dysfunctionPregnancy at term or breastfeeding nursing infants with G6PD deficiency or hyperbilirubinemia
| 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. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) or 'Safe with caution' |
| 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. |
| 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. |
| Food/Dietary |
| Avoid high-potassium foods (e.g., bananas, oranges, potatoes) if patient is on concurrent potassium-sparing diuretics or has renal impairment, as sulfamethoxazole may increase potassium levels. No significant food interactions otherwise, but maintain adequate hydration. |
| Clinical Pearls | Sulfamethoxazole is often combined with trimethoprim (co-trimoxazole) for synergy. Monitor for hypersensitivity reactions, especially in patients with sulfa allergies. Use with caution in patients with folate deficiency, G6PD deficiency, or renal impairment. Adjust dose in CrCl 15-30 mL/min; contraindicated if CrCl <15 mL/min. Avoid in infants <2 months due to risk of kernicterus. May potentiate warfarin, sulfonylureas, and phenytoin. |
| Patient Advice | Take with a full glass of water to prevent crystalluria and maintain adequate fluid intake. · Complete the full course even if symptoms improve to prevent resistance. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · Report any rash, sore throat, fever, or unusual bleeding immediately. · Notify your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not take if you have a known allergy to sulfonamides or thiazide diuretics. |