SULFANILAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFANILAMIDE (SULFANILAMIDE).
Competitive inhibitor of dihydropteroate synthase, blocking para-aminobenzoic acid (PABA) incorporation into dihydropteroic acid, thereby inhibiting bacterial folic acid synthesis.
| Metabolism | Hepatic acetylation (N-acetyltransferase) and glucuronidation; sulfanilamide is acetylated to N4-acetylsulfanilamide, which is inactive. |
| Excretion | Primarily renal via glomerular filtration and tubular secretion; ~50-70% excreted unchanged in urine; biliary/fecal excretion minimal (<5%). |
| Half-life | Terminal elimination half-life: 7-12 hours; prolonged in renal impairment (up to 24-48 hours). |
| Protein binding | ~10-20% bound to albumin. |
| Volume of Distribution | 0.2-0.4 L/kg; distributes widely but primarily in extracellular fluid. |
| Bioavailability | Oral: 70-100% (well absorbed). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: immediately (within minutes). |
| Duration of Action | 12-24 hours (dose-dependent); sustained-release formulations: up to 24 hours. |
| Molecular Weight | 172.2 |
2-4 g orally initially, then 2-4 g every 4-6 hours, not to exceed 12 g/day; intravenous: 4-8 g/day in divided doses every 6-8 hours.
| Dosage form | CREAM |
| Renal impairment | CrCl 10-50 mL/min: administer 75-100% of normal dose every 12-24 hours; CrCl <10 mL/min: administer 50-75% of normal dose every 24-48 hours. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use due to risk of hepatotoxicity. |
| Pediatric use | Loading dose 75 mg/kg, then 150 mg/kg/day divided every 6 hours, maximum 6 g/day. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 2 g loading dose, then 2 g every 6 hours) due to age-related renal impairment; monitor renal function and adjust based on CrCl. |
| 1st trimester | Avoid use due to risk of kernicterus in neonate and potential for teratogenic effects (folic acid antagonism). |
| 2nd trimester | Avoid use; sulfonamides can cause kernicterus in the newborn if given near term. |
| 3rd trimester | Contraindicated in third trimester due to risk of kernicterus in the neonate. Sulfonamides displace bilirubin from albumin, increasing risk of bilirubin encephalopathy. |
Clinical note
Comprehensive clinical and safety monograph for SULFANILAMIDE (SULFANILAMIDE).
| Placental transfer | Sulfanilamide crosses the placenta readily, achieving fetal serum concentrations 50-100% of maternal levels. |
| Breastfeeding | Sulfanilamide is excreted into breast milk in small amounts. In healthy, full-term infants, the risk of adverse effects is low, but caution is advised in infants with hyperbilirubinemia or G6PD deficiency. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
Sulfonamides have been associated with severe hypersensitivity reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Fatalities have occurred. Discontinue at first sign of rash.
| Serious Effects |
Hypersensitivity to sulfonamidesPregnancy (third trimester)Infants less than 2 months of age (except for congenital toxoplasmosis)Severe hepatic or renal impairmentPorphyria
| Precautions | Hemolytic anemia in G6PD deficiency; bone marrow suppression; hypersensitivity reactions including skin rashes and Stevens-Johnson syndrome; renal toxicity due to crystalluria; photosensitivity; discontinue if rash or signs of hypersensitivity occur. |
| Food/Dietary | No specific food interactions. However, avoid alcohol as it may increase risk of adverse effects. Maintain adequate hydration to prevent crystalluria. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Potential risk of kernicterus and hemolytic anemia in neonates, especially in G6PD deficiency. Avoid in third trimester due to competition with bilirubin for albumin binding sites and risk of neonatal hyperbilirubinemia. First trimester: limited data, avoid unless essential. Second trimester: may be used if benefit outweighs risk. Third trimester: contraindicated near term. |
| Fetal Monitoring | Monitor maternal CBC (for hemolytic anemia), renal and hepatic function. In newborns, monitor for jaundice, hemolytic anemia, and bilirubin levels. Consider G6PD status in mother and infant. |
| Fertility Effects | No reported adverse effects on fertility in animal studies or human data. Theoretical risk of folate antagonism; ensure adequate folic acid supplementation if used peri-conception. |
| Clinical Pearls | Sulfanilamide is a short-acting sulfonamide bacteriostatic antibiotic. It is now rarely used systemically due to resistance and availability of safer alternatives. Topical use for vaginal yeast infections is obsolete. Monitor for hypersensitivity reactions, crystalluria (ensure adequate hydration), and hemolysis in G6PD deficiency. Avoid in pregnancy (near term) and neonates due to risk of kernicterus. |
| Patient Advice | Take with a full glass of water and maintain high fluid intake throughout treatment to prevent kidney stones. · Complete the full course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen as sulfonamides may cause photosensitivity. · Report any rash, fever, sore throat, or unusual bleeding immediately. · Do not use leftover medication for future infections. · Inform your doctor if you have glucose-6-phosphate dehydrogenase deficiency or are pregnant/breastfeeding. |