GANTANOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GANTANOL (GANTANOL).
Sulfamethoxazole is a sulfonamide that inhibits bacterial dihydropteroate synthase, preventing folate synthesis. Trimethoprim inhibits bacterial dihydrofolate reductase, blocking tetrahydrofolate production. The combination produces sequential blockade of folate metabolism, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is metabolized primarily by N-acetylation and glucuronidation. Trimethoprim undergoes O-demethylation and oxidative metabolism. Both are excreted renally. |
| Excretion | Renal: 70% as unchanged drug; hepatic metabolism: 20% (glucuronidation); fecal: 10%. |
| Half-life | Terminal elimination half-life: 8-12 hours in healthy adults; prolonged in renal impairment (up to 24-36 hours in CrCl <30 mL/min). |
| Protein binding | 85-90% primarily to albumin. |
| Volume of Distribution | 0.15-0.3 L/kg; indicates limited extravascular distribution, primarily confined to plasma and interstitial fluid. |
| Bioavailability | Oral: 90-95%; Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 15-30 minutes. |
| Duration of Action | 12-24 hours; clinical effect persists for the dosing interval due to active metabolites. |
800 mg orally every 12 hours for 5-7 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: 800 mg every 24 hours. CrCl 15-29 mL/min: 800 mg every 48 hours. CrCl <15 mL/min or hemodialysis: 800 mg every 48-72 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: use contraindicated. |
| Pediatric use | 15 mg/kg orally every 6 hours for children 2 months to 12 years; maximum 2 g/day. |
| Geriatric use | Use with caution; start at 400 mg every 12 hours due to age-related renal decline. Monitor for toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GANTANOL (GANTANOL).
| Breastfeeding | Sulfamethoxazole is excreted into breast milk with a milk-to-plasma ratio of approximately 0.1. Based on limited data, not recommended in nursing mothers at term due to potential for neonatal kernicterus and hemolysis in G6PD-deficient infants; caution if used in preterm or jaundiced infants. |
| Teratogenic Risk | First trimester: Sulfonamides cross the placenta; risk of kernicterus in neonates if used near term. Animal studies show cleft palate and other anomalies at high doses. Human data insufficient; avoid use in first trimester unless benefit outweighs risk. Second/third trimester: Risk of neonatal jaundice and hemolytic anemia in G6PD deficiency; contraindicated after 38 weeks or near delivery due to kernicterus risk. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis have occurred. Also associated with fatal hematologic toxicities (e.g., agranulocytosis, aplastic anemia). Coadministration with methotrexate increases risk of megaloblastic anemia.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any component. History of drug-induced hypersensitivity reactions. Severe hepatic impairment. Severe renal impairment (CrCl <15 mL/min) not on dialysis. Megaloblastic anemia due to folate deficiency. Pregnancy (especially first trimester) and lactation (near term). Concurrent use with dofetilide.
| Precautions | Hypersensitivity and skin reactions (discontinue at first sign of rash). Hemolysis in G6PD-deficient patients. Risk of hepatotoxicity, including cholestatic jaundice and hepatic necrosis. Photosensitivity. Severe renal and hepatic impairment. Use caution in elderly, folate-deficient patients, and those with megaloblastic anemia. Possible hyperkalemia with high-dose treatment in renal impairment. |
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| Fetal Monitoring | Monitor complete blood count, renal function, liver enzymes, and bilirubin levels. Assess for fetal distress or preterm labor. In newborn, monitor for jaundice, anemia, and signs of kernicterus. |
| Fertility Effects | No significant adverse effects on fertility reported in animal studies or human data. Sulfonamides may rarely cause reversible oligospermia in males. |