SULFISOXAZOLE DIOLAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFISOXAZOLE DIOLAMINE (SULFISOXAZOLE DIOLAMINE).
Sulfisoxazole diolamine is a sulfonamide antibiotic that competitively inhibits dihydropteroate synthase, blocking the conversion of p-aminobenzoic acid (PABA) to dihydropteroic acid, thereby inhibiting bacterial folate synthesis and nucleic acid production.
| Metabolism | Primarily acetylated in the liver via N-acetyltransferase; also undergoes glucuronidation. The major metabolite is N4-acetylsulfisoxazole. Renal excretion of unchanged drug and metabolites. |
| Excretion | Renal: 70-100% (primarily as unchanged drug and acetylated metabolite); Biliary/Fecal: <5% |
| Half-life | 5-10 hours (prolonged in renal impairment; normal half-life in adults ~6 hours) |
| Protein binding | 50-70% (primarily to albumin) |
| Volume of Distribution | 0.15-0.3 L/kg (low Vd, indicates distribution primarily in extracellular fluid; does not penetrate CSF well unless inflamed) |
| Bioavailability | Oral: 90-100% (well absorbed; >95% absorbed from GI tract) |
| Onset of Action | Oral: 2-4 hours (therapeutic concentrations achieved in urine); Ophthalmic: 30-60 minutes (topical antibacterial effect) |
| Duration of Action | Oral: 4-6 hours (dosing interval every 6 hours); Ophthalmic: 4-6 hours (sustained antibacterial activity in tears) |
2-4 g orally initially, followed by 4-8 g/day in 4-6 divided doses for urinary tract infections; 6-8 g/day in 4-6 divided doses for nocardiosis.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: administer 50% of usual dose every 12-24 hours; CrCl <10 mL/min: administer 50% of usual dose every 24-48 hours or avoid use. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment. |
| Pediatric use | Infants >2 months and children: initial dose 75 mg/kg, then 150 mg/kg/day in 4-6 divided doses; maximum 6 g/day. |
| Geriatric use | Start at lower end of dosing range; monitor renal function and adjust dose accordingly; increased risk of adverse effects due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULFISOXAZOLE DIOLAMINE (SULFISOXAZOLE DIOLAMINE).
| Breastfeeding | Sulfisoxazole is excreted into breast milk. The milk-to-plasma ratio (M/P) is not well established, but concentrations in milk are estimated to be about 20-30% of maternal plasma levels. The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency, hyperbilirubinemia, or high bilirubin levels, as sulfonamides can displace bilirubin and cause kernicterus in infants. Avoid in nursing premature infants or those with jaundice. |
| Teratogenic Risk | Sulfisoxazole diolamine is a sulfonamide antibiotic. Use during pregnancy is generally avoided due to potential risks. First trimester: Sulfonamides have been associated with a possible increased risk of neural tube defects in some studies, but data are conflicting; however, the drug crosses the placenta. Second and third trimesters: There is a risk of kernicterus in the neonate because sulfonamides displace bilirubin from plasma proteins, potentially causing jaundice and bilirubin encephalopathy. The drug is contraindicated at term and during labor due to the risk of neonatal jaundice. |
■ FDA Black Box Warning
Sulfonamides, including sulfisoxazole diolamine, have been associated with fatal hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and agranulocytosis. They are contraindicated in patients with a known hypersensitivity to sulfonamides.
| Serious Effects |
Hypersensitivity to sulfonamides or any component of the formulation. Porphyria. Pregnancy near term (may cause kernicterus). Lactation (use caution; American Academy of Pediatrics considers compatible, but manufacturer contraindicates). Infants <2 months of age (except for treatment of congenital toxoplasmosis). Concurrent use with methenamine (risk of crystalluria).
| Precautions | May cause severe hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, and drug fever. Risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. May cause kernicterus in neonates, especially premature infants. Monitor renal and hepatic function. Use caution in patients with hepatic or renal impairment. |
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| Fetal Monitoring | Monitor: Renal function (serum creatinine, BUN), urinalysis for crystalluria, complete blood count for hematologic toxicity (e.g., agranulocytosis, aplastic anemia), and signs of hypersensitivity (fever, rash). In pregnancy: Assess fetal growth and well-being if used during gestation. Neonates exposed near term: Monitor bilirubin levels for hyperbilirubinemia and signs of kernicterus. |
| Fertility Effects | No specific studies on sulfisoxazole diolamine and human fertility. Sulfonamides have not been reported to adversely affect fertility in animal studies. However, antibacterial agents may transiently affect fertility if they cause significant systemic illness or sperm motility impairment in males, but evidence is lacking for sulfisoxazole. |