SULFISOXAZOLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).
Sulfisoxazole is a sulfonamide antibiotic that inhibits bacterial dihydropteroate synthase, blocking the synthesis of dihydrofolic acid and ultimately inhibiting bacterial folate synthesis and DNA replication.
| Metabolism | Primarily metabolized in the liver via acetylation and glucuronidation; also undergoes N4-acetylation. |
| Excretion | Renal excretion accounts for 70-85% of elimination, predominantly as unchanged drug (30-50%) and the N4-acetyl metabolite (15-30%). Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 5-7 hours in adults with normal renal function; prolonged to 12-20 hours in renal impairment (CrCl <30 mL/min). |
| Protein binding | 50-60% bound to serum albumin. |
| Volume of Distribution | 0.25-0.5 L/kg; distributes widely including CSF (30-80% of serum levels), pleural, and peritoneal fluids. |
| Bioavailability | Oral: 90-100% (well absorbed, but delayed by food). Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours after first dose; Intravenous: 30-60 minutes after infusion start. |
| Duration of Action | Duration is 6-12 hours for oral dosing, requiring dosing every 6 hours for continuous therapy. Renal impairment prolongs duration. |
| Molecular Weight | 267.3 |
1-2 g orally once, then 500 mg-1 g orally every 4-6 hours; maximum 6 g/day.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: give q8-12h; CrCl <10 mL/min: give q12-24h. |
| Liver impairment | No specific recommendations; use caution in severe hepatic impairment. |
| Pediatric use | >2 months: initial dose 75 mg/kg, then 150 mg/kg/day divided q4-6h; maximum 6 g/day. |
| Geriatric use | Start at lower end of dosing range due to age-related renal decline; monitor renal function. |
| 1st trimester | Avoid during first trimester due to risk of teratogenicity (folate antagonism, kernicterus potential). Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; risk of neonatal jaundice and kernicterus when given near term. Consider alternative if possible. |
| 3rd trimester | Avoid during third trimester (especially after 36 weeks) due to risk of kernicterus in the newborn by displacing bilirubin from albumin. |
Clinical note
Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).
| Placental transfer | Extensive placental transfer; concentrations in fetal plasma reach 50-90% of maternal levels. Competes for bilirubin binding sites, increasing risk of kernicterus. |
| Breastfeeding | Sulfisoxazole is excreted into breast milk in small amounts, but may cause kernicterus in infants with G6PD deficiency, hyperbilirubinemia, or prematurity. Use caution, monitor infant for jaundice, and consider alternatives. |
■ FDA Black Box Warning
Fatalities have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
| Serious Effects |
Hypersensitivity to sulfonamides or any componentInfants <2 months of age (except for congenital toxoplasmosis)Pregnancy at term (risk of kernicterus)Breastfeeding infants with hyperbilirubinemia or G6PD deficiencySevere hepatic or renal impairment
| Precautions | Increased risk of severe hypersensitivity reactions, especially in patients with HIV or G6PD deficiency, Hematologic toxicity including agranulocytosis and aplastic anemia, Hepatic injury and hepatitis, Renal impairment and crystalluria, Photosensitivity and skin reactions, Use in pregnancy: risk of kernicterus in neonates; avoid near term, Sulfonamide cross-sensitivity |
| Food/Dietary | Avoid alcohol while taking sulfisoxazole as it may cause adverse reactions. No significant food interactions reported; maintain adequate fluid intake. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - Use with caution; avoid in preterm or jaundiced infants. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Theoretical risk of teratogenicity due to folate antagonism; limited human data show no clear increase in major malformations. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; contraindicated near term (after 37 weeks) and during labor. |
| Fetal Monitoring | Maternal: CBC with differential, platelet count, urinalysis, renal function tests, liver function tests. Monitor for hypersensitivity reactions, crystalluria (ensure adequate hydration). Fetal: Ultrasound for growth and development if used in first trimester; monitor neonatal bilirubin and signs of kernicterus if used near term. |
| Fertility Effects | No direct evidence of adverse effects on fertility in humans. In animal studies, high doses have shown impaired fertility, but relevance to humans is unknown. |
| Clinical Pearls | Sulfisoxazole is a short-acting sulfonamide antibiotic; ensure adequate hydration to prevent crystalluria. Monitor for hypersensitivity reactions, including Stevens-Johnson syndrome. Use with caution in patients with G6PD deficiency due to risk of hemolytic anemia. Adjust dose in renal impairment (CrCl <50 mL/min). |
| Patient Advice | Take with a full glass of water and drink plenty of fluids throughout the day to prevent kidney problems. · Complete the full course of treatment even if you feel better. · Avoid prolonged sun exposure and use sunscreen; this drug can increase sun sensitivity. · Report any skin rash, sore throat, fever, or unusual bleeding immediately. · Do not take if you are allergic to sulfa drugs or have a history of sulfa allergy. |