SULFADIAZINE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Competitive inhibitor of dihydropteroate synthase, blocking the synthesis of folic acid in bacteria.
| Metabolism | Hepatic acetylation (N-acetyltransferase) and glucuronidation. |
| Excretion | Renal excretion of unchanged drug (50-70%) and acetylated metabolites; minor biliary/fecal (<5%) |
| Half-life | Terminal elimination half-life 10-20 hours (prolonged in renal impairment; may require dose adjustment) |
| Protein binding | 50-70% bound to albumin |
| Volume of Distribution | 0.6-1.0 L/kg (distributes widely, including CSF with inflamed meninges) |
| Bioavailability | Oral: 70-100% (well absorbed; food may reduce rate) |
| Onset of Action | Oral: 2-4 hours (time to therapeutic serum concentrations); IV: immediate |
| Duration of Action | 12-24 hours (serum levels above MIC for susceptible organisms); prolonged with renal impairment |
| Molecular Weight | 250.28 |
Oral: 2-4 g initially, then 1 g every 4-6 hours for mild to moderate infections; for severe infections, 4 g initially followed by 1.5 g every 4 hours. IV: Not available in IV form in the US; if using oral suspension, adjust accordingly.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: standard dosing; CrCl 15-50 mL/min: administer 50% of normal dose at normal intervals or normal dose at extended intervals (every 12-24 hours); CrCl <15 mL/min: avoid use or administer 50% of normal dose every 24-48 hours; hemodialysis: administer after dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment necessary; Child-Pugh Class B and C: use with caution, consider dose reduction due to impaired metabolism, no specific guidelines; monitor liver function and adjust based on toxicity. |
| Pediatric use | Neonates (≥2 months): 75 mg/kg initially, then 150 mg/kg/day divided every 6 hours; maximum 6 g/day. Infants and Children (2 months to 12 years): 50-75 mg/kg initially (max 4 g), then 150 mg/kg/day divided every 4-6 hours (max 6 g/day). |
| Geriatric use | Elderly patients may have reduced renal function; start with lower doses (e.g., 500 mg every 6 hours) and titrate based on renal function and response; monitor for hypersensitivity and renal toxicity. |
| 1st trimester | Avoid in first trimester; teratogenic risk (folic acid antagonism) and possible kernicterus risk; use only if clearly needed and no safer alternative. |
| 2nd trimester | Use only if benefit outweighs risk; risk of kernicterus theoretical but generally avoided in pregnancy, especially near term. |
| 3rd trimester | Contraindicated in third trimester due to risk of kernicterus in the newborn; displaces bilirubin from protein binding. |
Clinical note
May potentiate the effects of warfarin and sulfonylureas Can cause crystalluria and Stevens-Johnson syndrome.
| Placental transfer | Sulfadiazine crosses the placenta; cord blood concentrations approximate maternal levels due to rapid placental transfer. |
| Breastfeeding | Sulfadiazine is excreted into breast milk in low concentrations. In healthy term infants, risk is low, but caution is advised in preterm infants, those with hyperbilirubinemia, or G6PD deficiency due to potential for kernicterus and hemolysis. Manufacturer advises caution. |
■ FDA Black Box Warning
None.
| Common Effects | other infections |
| Serious Effects |
Hypersensitivity to sulfonamides or any componentPorphyria (may precipitate acute attack)Third trimester of pregnancy (risk of kernicterus)Infants <2 months of age (except for congenital toxoplasmosis treatment)Significant hepatic or renal impairment (avoid if severe)
| Precautions | Severe hypersensitivity reactions (including Stevens-Johnson syndrome), hematologic toxicity (agranulocytosis, aplastic anemia), renal toxicity due to crystalluria, kernicterus in neonates, hemolytic anemia in G6PD deficiency, and photosensitivity. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., citrus fruits, tomatoes, carbonated drinks) as they increase risk of crystalluria. Avoid alcohol as it may cause disulfiram-like reaction. Stay well hydrated; drink at least 2-3 liters of fluid daily unless contraindicated. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - Use caution, especially in high-risk infants. |
| Teratogenic Risk | First trimester: Sulfadiazine crosses placenta. Risk of neural tube defects, cleft palate, and cardiovascular anomalies in animal studies; human data limited but potential risk due to folate antagonism. Second trimester: Avoid near term due to risk of kernicterus from bilirubin displacement. Third trimester: Contraindicated in pregnancy near term (after 38 weeks) and during labor due to risk of kernicterus in neonate. |
| Fetal Monitoring | Maternal: Complete blood count (CBC) with differential, renal function, liver function tests, urinalysis for crystalluria. Fetal: Ultrasound for growth and anatomy if used in first trimester. Neonatal: Monitor for jaundice, bilirubin levels, and signs of hemolysis or kernicterus after birth. |
| Fertility Effects | Sulfadiazine may impair fertility by interfering with folate metabolism, potentially affecting spermatogenesis and oogenesis. Folate supplementation may mitigate risk. No direct evidence of permanent infertility. |
| Clinical Pearls | Sulfadiazine is a short-acting sulfonamide used primarily in combination with pyrimethamine for toxoplasmosis. Monitor for crystalluria by ensuring adequate hydration and urine output; alkalinize urine to pH >7 if needed. Avoid in patients with G6PD deficiency due to risk of hemolytic anemia. Caution in renal impairment; adjust dose if CrCl <30 mL/min. Check for sulfa allergy history due to cross-reactivity with other sulfonamides. |
| Patient Advice | Take with a full glass of water and maintain high fluid intake to prevent kidney stones. · Finish the entire prescribed course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen as sulfadiazine can cause photosensitivity. · Report any rash, fever, sore throat, or unusual bleeding/bruising immediately. · Do not take with bismuth subsalicylate or acidic foods as they may reduce absorption. |