SULFOSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFOSE (SULFOSE).
Sulfonamide antibiotic; inhibits bacterial dihydropteroate synthase, blocking folate synthesis and bacterial growth.
| Metabolism | Primarily hepatic via N-acetylation and glucuronidation; major enzyme NAT2. |
| Excretion | Renal: ~90% as unchanged drug via glomerular filtration; biliary/fecal: <10%. |
| Half-life | Terminal elimination half-life: 3-4 hours in patients with normal renal function; prolonged to 20-50 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 25-30% bound primarily to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 70-80% (first-pass metabolism minimal). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: Immediate (within 5 minutes). |
| Duration of Action | Oral: 6-8 hours; Intravenous: 4-6 hours. Duration is prolonged in renal impairment. |
| Molecular Weight | Sulfadiazine: 250.27 Da; Pyrimethamine: 248.71 Da. Combination product: component weights. |
Meningococcal meningitis: 100 mg/kg/day intravenously in 4 divided doses (maximum 6 g/day). For other infections: 2-4 g/day IV/IM in 3-4 divided doses.
| Dosage form | SUSPENSION |
| Renal impairment | GFR 30-50 mL/min: no adjustment. GFR 15-29 mL/min: 2 g every 12 hours. GFR <15 mL/min: 2 g every 24 hours. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 75% of normal dose. Child-Pugh C: 50% of normal dose. |
| Pediatric use | Neonates: 100 mg/kg/day IV divided every 12 hours. Infants >1 month: 100 mg/kg/day IV divided every 6 hours. Children: 100-200 mg/kg/day IV divided every 6 hours; maximum 6 g/day. |
| Geriatric use | No specific dose adjustment, but monitor renal function; reduce dose based on creatinine clearance. |
| 1st trimester | Sulfose (sulfadiazine/pyrimethamine) is contraindicated in the first trimester due to teratogenic risk from pyrimethamine (folate antagonist). Use only if benefit clearly outweighs risk. |
| 2nd trimester | Use with caution in second trimester. Monitor for kernicterus risk due to sulfonamide; avoid near term. |
| 3rd trimester | Contraindicated in third trimester near term due to risk of kernicterus and hemolytic anemia in neonate. |
Clinical note
Comprehensive clinical and safety monograph for SULFOSE (SULFOSE).
| Placental transfer | Both sulfadiazine and pyrimethamine cross the placenta. Pyrimethamine reaches therapeutic levels in fetal circulation; sulfadiazine binds to plasma proteins but still crosses. Documented effective transplacental transfer. |
| Breastfeeding | Sulfadiazine and pyrimethamine are excreted in breast milk. Potential for significant toxicity in nursing infants: sulfadiazine may cause kernicterus in jaundiced or G6PD-deficient infants; pyrimethamine may cause hemolytic anemia. Avoid breastfeeding during therapy; if essential, monitor infant for adverse effects and consider expressing and discarding milk. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.
| Serious Effects |
Hypersensitivity to sulfonamides or pyrimethamineMegaloblastic anemia due to folate deficiencyFirst trimester pregnancy (relative contraindication; only if benefit outweighs risk)Severe hepatic or renal impairmentNeonates (<2 months of age due to sulfonamide competition with bilirubin)
| Precautions | Hypersensitivity reactions, severe skin reactions, hematologic toxicity, hepatic and renal impairment, photosensitivity, glucose-6-phosphate dehydrogenase deficiency, sulfonamide allergy, pregnancy (avoid near term), lactation. |
| Food/Dietary | Avoid acidic foods (e.g., citrus fruits, tomatoes) as they may increase crystalluria risk. No significant food restrictions otherwise. |
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| Lactation Rating | L5 (Contraindicated) or Avoid |
| Teratogenic Risk | SULFOSE contains sulfamethoxazole and sulfadiazine, both FDA Pregnancy Category D. First trimester: Risk of neural tube defects, cardiovascular malformations, and cleft palate based on animal studies and limited human data. Second/third trimester: Risk of kernicterus in neonates due to bilirubin displacement from albumin; avoid near term. |
| Fetal Monitoring | Monitor maternal CBC, renal function, liver enzymes, and bilirubin levels. Fetal assessment: serial ultrasound for growth and anatomy; consider amniotic fluid volume assessment. Neonatal monitoring for jaundice, hemolysis, and kernicterus. |
| Fertility Effects | No significant impairment in fertility reported in animal studies. Sulfonamides may cause reversible sperm abnormalities in males at high doses. No documented effect on female fertility. |
| Clinical Pearls | SULFOSE is a sulfonamide antibiotic; ensure adequate hydration to prevent crystalluria. Monitor renal function and complete blood count due to risk of agranulocytosis. Avoid use in patients with G6PD deficiency due to hemolytic anemia risk. |
| Patient Advice | Take with full glass of water and maintain good fluid intake. · Complete the full course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen as sulfonamides may cause photosensitivity. · Report rash, sore throat, fever, or unusual bleeding immediately. |