GANTRISIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GANTRISIN (GANTRISIN).
Competitive inhibitor of dihydropteroate synthase, blocking para-aminobenzoic acid (PABA) incorporation into dihydropteroic acid, thereby inhibiting bacterial folate synthesis and nucleic acid production.
| Metabolism | Primarily hepatic via N4-acetylation and glucuronidation; major metabolite is N4-acetylsulfisoxazole. |
| Excretion | Renal: 70% as unchanged drug; hepatic metabolism: 30% as acetylated metabolites; biliary: <3% |
| Half-life | 7-12 hours (mean 10 hours); prolonged to 20-50 hours in renal impairment (CrCl <30 mL/min) |
| Protein binding | 98-99% (primarily to albumin; also to alpha-1-acid glycoprotein) |
| Volume of Distribution | 0.36 L/kg (range 0.28-0.44 L/kg); indicates distribution primarily in extracellular fluid |
| Bioavailability | Oral: 85-100% (well absorbed); IM: 70-80% (due to depot effect) |
| Onset of Action | Oral: 30-60 minutes (bacteriostatic effect); IV: immediate (within minutes) |
| Duration of Action | 12-24 hours (dose-dependent); clinical effect persists for 6-12 hours after single oral dose |
2-4 g orally initially, then 4-8 g daily in 3-6 divided doses
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: 50% of dose; CrCl <10 mL/min: 25% of dose |
| Liver impairment | No specific Child-Pugh based adjustments; use with caution in severe hepatic impairment |
| Pediatric use | >2 months: 75 mg/kg initially, then 120-150 mg/kg/day in 4-6 divided doses, max 6 g/day |
| Geriatric use | Consider age-related renal decline; adjust based on CrCl |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GANTRISIN (GANTRISIN).
| Breastfeeding | Sulfisoxazole (Gantrisin) is excreted into breast milk; M/P ratio approx 0.1–0.4. Risk of kernicterus in preterm or jaundiced infants, or G6PD deficiency. Generally contraindicated during breastfeeding in first month of life; may use with caution in older healthy infants, but alternatives preferred. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: risk of kernicterus in neonates, particularly if maternal bilirubin elevated; may cause hemolytic anemia in G6PD-deficient fetuses. Second/third trimester: increased risk of bilirubin displacement and kernicterus; caution in maternal sulfonamide hypersensitivity, rare reports of congenital malformations but not clearly attributable. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to sulfonamides or any component","Infants <2 months of age (except for congenital toxoplasmosis therapy with pyrimethamine)","Pregnancy at term and nursing mothers due to risk of kernicterus","Porphyria (may precipitate attack)","Severe hepatic or renal impairment"]
| Precautions | ["Fatalities due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias","Hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients","Renal toxicity due to crystalluria; maintain adequate fluid intake","Hepatotoxicity, including jaundice and hepatic necrosis","Hypersensitivity reactions including anaphylaxis, drug fever, and serum sickness","Prolonged or repeated use may lead to superinfection","May cause kernicterus in neonates; contraindicated in infants <2 months"] |
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| Fetal Monitoring | Monitor maternal bilirubin, LFTs, CBC with differential, and G6PD status in mother and fetus/newborn; fetal ultrasound for anomalies if exposure in first trimester; assess newborn for signs of kernicterus, hemolytic anemia, and hypersensitivity reactions. |
| Fertility Effects | No known direct impairment of fertility in humans; animal studies not indicative of adverse effects at therapeutic doses. |