SULFADIAZINE SODIUM
Clinical safety rating: avoid
May potentiate the effects of warfarin and sulfonylureas Can cause crystalluria and Stevens-Johnson syndrome.
Sulfadiazine is a competitive inhibitor of dihydropteroate synthase, blocking the conversion of p-aminobenzoic acid (PABA) to dihydropteroate, thereby inhibiting bacterial folic acid synthesis.
| Metabolism | Primarily hepatic metabolism via acetylation (N-acetyltransferase) and glucuronidation; also undergoes renal tubular reabsorption and elimination. |
| Excretion | Renal: 60-85% (via glomerular filtration and tubular secretion, with acetylation in liver reducing solubility and increasing crystalluria risk). Biliary/fecal: less than 15%. Unchanged drug and acetylated metabolites both excreted. |
| Half-life | Terminal elimination half-life: 10-20 hours (prolonged in renal impairment; context: requires dose adjustment in CrCl <50 mL/min). |
| Protein binding | 50-60% (primarily to albumin; decreased binding in uremia or hypoalbuminemia). |
| Volume of Distribution | 0.5-0.8 L/kg (extensive distribution into tissues, including CSF and placenta; Vd larger in neonates and children). |
| Bioavailability | Oral: 85-95% (well absorbed; food delays absorption but does not reduce extent). |
| Onset of Action | Intravenous: within 30 minutes (achievement of therapeutic CSF concentrations within 2-4 hours). Oral: 1-2 hours (peak concentration at 3-6 hours). |
| Duration of Action | Intravenous: 6-12 hours (dosing every 4-6 hours for systemic infections; with probenecid, duration may be extended). Oral: 6-8 hours (short half-life requires frequent dosing for sustained effect). |
2-4 g IV initially, then 1-2 g IV every 6-8 hours; oral dose: 2-4 g loading, then 1-2 g every 6 hours
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: administer every 8-12 hours; CrCl <10 mL/min: administer every 12-24 hours; hemodialysis: administer after dialysis |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment due to potential for reduced metabolism |
| Pediatric use | Neonates: 100 mg/kg IV once, then 50 mg/kg every 12 hours; Infants and children: 50-100 mg/kg IV loading dose, then 50-100 mg/kg/day divided every 6 hours; maximum 6 g/day |
| Geriatric use | Use with caution; monitor renal function and adjust dose based on creatinine clearance; avoid in patients with severe renal impairment |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
May potentiate the effects of warfarin and sulfonylureas Can cause crystalluria and Stevens-Johnson syndrome.
| FDA category | Positive |
| Breastfeeding | Sulfadiazine is excreted into breast milk. M/P ratio not reported. Use with caution in breastfeeding mothers of infants with G6PD deficiency, hyperbilirubinemia, or illness. Potential for kernicterus in neonates, particularly if premature or with hyperbilirubinemia. American Academy of Pediatrics considers compatible with breastfeeding, but avoid in preterm infants or those with hyperbilirubinemia. |
| Teratogenic Risk |
■ FDA Black Box Warning
Fatalities have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
| Common Effects | other infections |
| Serious Effects |
Hypersensitivity to sulfonamides, sulfonylureas, or thiazides; porphyria; severe hepatic or renal impairment; pregnancy at term and breastfeeding (risk of kernicterus); infants <2 months of age (except for congenital toxoplasmosis).
| Precautions | Monitor for hypersensitivity reactions, severe cutaneous adverse reactions (SCARs), hematologic toxicity, renal impairment (crystalluria), and photosensitivity. Use with caution in G6PD deficiency, hepatic impairment, and during pregnancy (risk of kernicterus in neonates). |
Loading safety data…
| Sulfadiazine sodium crosses the placenta. First trimester: Risk of teratogenicity not established; limited human data, animal studies show cleft palate at high doses. Second and third trimesters: Risk of kernicterus in neonates, especially near term, due to bilirubin displacement from albumin binding. Avoid use after 38 weeks gestation. |
| Fetal Monitoring | Monitor maternal CBC, renal function, and liver function tests. Assess for hypersensitivity reactions (Stevens-Johnson syndrome, hepatotoxicity). Fetal monitoring: Ultrasound for growth restriction if used long-term; avoid near term due to kernicterus risk. |
| Fertility Effects | No specific data on sulfadiazine sodium affecting fertility in humans. Animal studies have not shown impaired fertility at therapeutic doses. |