THIOSULFIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THIOSULFIL (THIOSULFIL).
Thiosulfil (sulfamethizole) is a sulfonamide antibiotic that inhibits bacterial dihydropteroate synthase, blocking folic acid synthesis and thereby nucleic acid production.
| Metabolism | Primarily hepatic metabolism via acetylation and glucuronidation; excreted renally as unchanged drug and metabolites. |
| Excretion | Renal: 70-90% as unchanged drug via glomerular filtration and tubular secretion. Biliary/fecal: <5%. |
| Half-life | Terminal elimination half-life is 2-4 hours in patients with normal renal function (creatinine clearance >80 mL/min); prolonged to 20-50 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 85-90% bound to serum albumin. |
| Volume of Distribution | 0.2-0.4 L/kg, indicating distribution primarily in extracellular fluid and low tissue penetration. |
| Bioavailability | Oral: 85-95% (well absorbed from gastrointestinal tract). |
| Onset of Action | Oral: 2-4 hours for therapeutic urinary concentrations. |
| Duration of Action | 12-24 hours based on urinary concentrations above MIC for susceptible organisms; requires q6-8h dosing for sustained effect. |
| Molecular Weight | 421.53 |
500 mg orally twice daily for 10-14 days.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 500 mg every 24-36 hours; GFR 10-29 mL/min: 500 mg every 36-48 hours; GFR <10 mL/min: 500 mg every 48-72 hours or consider alternative. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 250 mg orally twice daily; Child-Pugh C: not recommended. |
| Pediatric use | For children >2 months: 25-50 mg/kg/day orally divided every 12 hours; maximum 4 g/day. For infants <2 months: not recommended. |
| Geriatric use | Start at 250 mg orally twice daily; increase to 500 mg twice daily based on tolerance and renal function; monitor for hypersensitivity and renal impairment. |
| 1st trimester | Avoid during first trimester due to potential teratogenic effects based on animal studies and case reports of congenital abnormalities (e.g., cleft palate). |
| 2nd trimester | Use only if clearly needed; sulfonamides compete for bilirubin binding sites and may increase risk of kernicterus in neonates if used near term. |
| 3rd trimester | Contraindicated near term (after 32 weeks) due to risk of kernicterus in the newborn. |
Clinical note
Comprehensive clinical and safety monograph for THIOSULFIL (THIOSULFIL).
| Placental transfer | Sulfonamides cross the placenta readily, achieving fetal serum concentrations approximately 50-80% of maternal levels. |
| Breastfeeding | Thiosulfil is excreted into breast milk in small amounts. In healthy full-term infants, risk of kernicterus is low, but caution is advised in premature infants or those with hyperbilirubinemia or G6PD deficiency. Monitor infant for jaundice. |
■ FDA Black Box Warning
Sulfonamides have been associated with severe hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hematologic toxicities. Use caution in patients with history of sulfonamide allergy.
| Serious Effects |
Hypersensitivity to sulfonamidesPorphyriaSevere hepatic or renal impairmentPregnancy at term or nursing mothers of premature/hyperbilirubinemic infantsConcurrent use with methenamine (increased risk of crystalluria)
| Precautions | Monitor for hypersensitivity reactions, hematologic effects (agranulocytosis, aplastic anemia), renal toxicity, and photosensitivity. Use cautiously in patients with renal impairment or G6PD deficiency. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., cranberry juice, citrus) as they may increase risk of crystalluria. Maintain adequate hydration. No significant food-drug interactions reported aside from the need for alkalinization of urine to prevent crystallization. Avoid alcohol as it may increase risk of side effects. |
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| Lactation Rating | L3 (Moderately Safe) - limited data but minimal risk in healthy term infants; avoid in high-risk situations. |
| Teratogenic Risk | Pregnancy category D. Sulfonamides cross the placenta and may cause kernicterus in the newborn if used near term. Avoid use in first and third trimesters; second trimester use only if clearly needed. |
| Fetal Monitoring | Monitor maternal complete blood count, renal function, and bilirubin levels. Fetal monitoring for jaundice and kernicterus if maternal use near term. Assess for hypersensitivity reactions. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment. |
| Clinical Pearls | THIOSULFIL (sulfamethizole) is a short-acting sulfonamide used primarily for urinary tract infections. Obtain baseline renal and hepatic function. Ensure adequate fluid intake (≥2 L/day) to prevent crystalluria. Monitor for hypersensitivity reactions, especially in patients with sulfa allergies. Note that sulfamethizole may potentiate the effects of warfarin, oral hypoglycemics, and methotrexate. Use with caution in G6PD deficiency due to risk of hemolytic anemia. |
| Patient Advice | Take this medication exactly as prescribed, with a full glass of water. · Drink plenty of fluids (at least 8 glasses per day) to prevent kidney stones. · Complete the full course even if you feel better to prevent antibiotic resistance. · Avoid prolonged sun exposure; use sunscreen as this drug can increase photosensitivity. · Report any rash, fever, sore throat, unusual bleeding, or yellowing of skin/eyes immediately. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · This medication may cause dizziness; avoid driving until you know how it affects you. · Do not take with antacids containing magnesium trisilicate as they reduce absorption. |