SULLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULLA (SULLA).
SULLA (sulfamethoxazole/trimethoprim) inhibits bacterial dihydropteroate synthase and dihydrofolate reductase, sequentially blocking folate synthesis and thereby nucleic acid production.
| Metabolism | Sulfamethoxazole is primarily metabolized via N4-acetylation; trimethoprim undergoes hepatic metabolism via demethylation and oxidation. Both are eliminated renally. |
| Excretion | Renal: 70-90% unchanged; biliary/fecal: 5-10% |
| Half-life | 6-12 hours; prolonged in renal impairment (up to 30 hours) |
| Protein binding | 80% bound to albumin |
| Volume of Distribution | 2-3 L/kg; large distribution suggests extravascular penetration |
| Bioavailability | Oral: 100% (well absorbed) |
| Onset of Action | Oral: 2-4 hours; Intravenous: 5-15 minutes |
| Duration of Action | 6-12 hours; may extend in renal dysfunction |
100 mg orally once daily, increased to 200 mg daily if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: 100 mg every 48 hours. GFR <30 mL/min: 100 mg twice weekly. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: use with caution, dose reduction by 50%. |
| Pediatric use | Not established in patients <18 years. |
| Geriatric use | Start at 100 mg daily; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULLA (SULLA).
| Breastfeeding | Sulfadiazine is excreted into breast milk in low concentrations. M/P ratio not established for sulfadiazine specifically, but sulfonamides generally have M/P ratios ranging from 0.5 to 0.8. Theoretical risk of kernicterus in premature infants or those with G6PD deficiency. Caution advised; use only if benefit outweighs risk. |
| Teratogenic Risk | SULLA (sulfadiazine) is a sulfonamide antibiotic. First trimester: Limited data, but sulfonamides are generally avoided due to potential teratogenicity (e.g., cleft palate in animal studies); risk cannot be excluded. Second and third trimesters: Risk of kernicterus in neonates if administered near term due to displacement of bilirubin from albumin; avoid use after 32 weeks gestation. Overall, FDA Pregnancy Category C. |
■ FDA Black Box Warning
Fatalities associated with sulfonamide hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Avoid use in patients with a history of sulfonamide allergy.
| Serious Effects |
Hypersensitivity to sulfonamides or trimethoprim, megaloblastic anemia due to folate deficiency, severe hepatic damage, marked renal impairment (CrCl <15 mL/min not recommended), pregnancy (first trimester and near term), lactation, infants <2 months of age.
| Precautions | Hypersensitivity reactions, severe cutaneous adverse reactions (SCAR), hematologic toxicity, hepatic necrosis, renal impairment (dose adjustment), folate deficiency, hyperkalemia (especially in elderly), hypoglycemia, photosensitivity. |
Loading safety data…
| Fetal Monitoring | Maternal: Complete blood count, renal function, liver function tests, and urinalysis due to risk of hematologic toxicity (agranulocytosis, hemolytic anemia) and crystalluria; monitor for hypersensitivity reactions (Stevens-Johnson syndrome). Fetal: Ultrasound for growth and potential anomalies if administered in first trimester; assess for jaundice or signs of kernicterus if used near term. |
| Fertility Effects | No significant impact on fertility reported in human or animal studies. Sulfonamides are not known to adversely affect spermatogenesis or oogenesis. |