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) |
| Molecular Weight | 267.31 |
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 | Contraindicated due to risk of kernicterus and teratogenicity (folate antagonism). |
| 2nd trimester | Avoid use, especially near term, due to risk of kernicterus in newborn. |
| 3rd trimester | Contraindicated (risk of kernicterus and hemolytic anemia in G6PD-deficient infants). |
Clinical note
Comprehensive clinical and safety monograph for SULFISOXAZOLE DIOLAMINE (SULFISOXAZOLE DIOLAMINE).
| Placental transfer | Crosses placenta; achieves fetal serum levels 50-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; potential for kernicterus in jaundiced or G6PD-deficient infants. Use caution, especially in preterm or ill infants. |
| Lactation Rating |
■ 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 sulfonamidesPorphyriaSevere hepatic or renal impairmentInfants <2 months of age (except for congenital toxoplasmosis)Pregnancy at term and nursing mothers (risk of kernicterus)
| 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. |
| Food/Dietary | No significant food interactions; however, maintain adequate fluid intake. Avoid alcohol as it may increase risk of side effects. |
Loading safety data…
| L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Clinical Pearls | Sulfisoxazole diolamine is a sulfonamide antibiotic; ensure adequate hydration to prevent crystalluria; monitor for hypersensitivity reactions, especially in patients with sulfa allergy; can cause photosensitivity; not for use in infants less than 2 months of age due to risk of kernicterus; adjust dose in renal impairment. |
| Patient Advice | Take with a full glass of water and stay well-hydrated to prevent kidney stones. · Finish the entire course even if you feel better. · Avoid prolonged sun exposure and use sunscreen. · Report any skin rash, fever, sore throat, or unusual bleeding. · This medication may make birth control pills less effective; use additional contraception. |