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 |
| Molecular Weight | 267.3 Da |
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 | Sulfisoxazole crosses the placenta. Avoid use in the first trimester due to potential teratogenic effects (folate antagonism) and risk of neural tube defects. |
| 2nd trimester | Use only if clearly needed. Risk of kernicterus in the newborn if used near term due to displacement of bilirubin from albumin. |
| 3rd trimester | Contraindicated in third trimester due to risk of jaundice and hemolytic anemia in the neonate. |
Clinical note
Comprehensive clinical and safety monograph for GANTRISIN (GANTRISIN).
| Placental transfer | Sulfisoxazole readily crosses the placenta with maternal-fetal serum concentration ratios approaching 1.0, indicating extensive transfer. |
| Breastfeeding | Sulfisoxazole is excreted into breast milk. Use caution in nursing mothers of infants with G6PD deficiency or hyperbilirubinemia. The American Academy of Pediatrics considers sulfonamides as compatible with breastfeeding but avoid in ill or stressed infants. |
■ FDA Black Box Warning
None
| Serious Effects |
History of hypersensitivity to sulfonamidesInfants less than 2 months of age (except for congenital toxoplasmosis)Pregnancy at term or third trimesterLactation in infants with G6PD deficiency or hyperbilirubinemiaSevere 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 |
| Food/Dietary | Avoid alcohol as it may cause disulfiram-like reaction. No specific food interactions; maintain adequate fluid intake. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Gantrisin (sulfisoxazole) is a short-acting sulfonamide antibiotic. It is highly protein-bound and undergoes hepatic acetylation; acetylated metabolites may crystallize in urine. Ensure adequate hydration to prevent crystalluria. Monitor renal function and CBC due to risk of agranulocytosis. Contraindicated in infants <2 months and in pregnancy near term due to kernicterus risk. |
| 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 medication even if you feel better. · Avoid prolonged sun exposure and use sunscreen; this drug can cause photosensitivity. · Report any skin rash, sore throat, fever, unusual bleeding, or bruising immediately. · Do not take if you have a history of sulfa allergy. |