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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULFANILAMIDE (SULFANILAMIDE).
| Breastfeeding | Excreted into breast milk in low amounts. M/P ratio approximately 0.1-0.2. Risk of kernicterus in neonates with G6PD deficiency or hyperbilirubinemia. Use with caution, avoid in premature infants or those with hyperbilirubinemia. American Academy of Pediatrics considers compatible with breastfeeding. |
| 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. |
■ 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 sulfonamides or any component; porphyria; hepatic or renal impairment; pregnancy (third trimester) due to risk of kernicterus; lactation; children less than 2 months of age.
| 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. |
Loading safety data…
| 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. |