SULFATRIM-DS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFATRIM-DS (SULFATRIM-DS).
Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking folate synthesis. Trimethoprim inhibits bacterial dihydrofolate reductase, inhibiting reduction of dihydrofolate to tetrahydrofolate. Sequential blockade of folate metabolism exerts bactericidal effect.
| Metabolism | Sulfamethoxazole is primarily metabolized via N-acetylation and glucuronidation; trimethoprim is metabolized by oxidation (CYP3A4) and conjugation. |
| Excretion | Renal: 50-70% of total sulfamethoxazole (SMX) and 30% of trimethoprim (TMP) as unchanged drug via glomerular filtration and tubular secretion; 20-40% of SMX as N4-acetylated metabolite; biliary excretion accounts for <5%. |
| Half-life | SMX: 9-11 hours (terminal); TMP: 8-10 hours; prolonged in renal impairment (creatinine clearance <30 mL/min: up to 20-30 hours for both). |
| Protein binding | SMX: ~70% bound to albumin; TMP: ~44% bound to albumin. |
| Volume of Distribution | SMX: 0.15-0.2 L/kg; TMP: 1.5-2.5 L/kg; TMP distributes widely into tissues (e.g., lung, kidney, prostate) and exceeds serum concentrations. |
| Bioavailability | Oral: 90-100% for both components (well absorbed from GI tract); IV: 100%. |
| Onset of Action | Oral: 1-4 hours for peak plasma concentrations and clinical effect; IV: immediate for systemic effect. |
| Duration of Action | 12 hours for bacteriostatic effect; dosing every 12 hours maintains therapeutic concentrations; duration may extend with renal impairment. |
One double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) orally every 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: 50% of usual dose every 12 hours; CrCl <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: caution, consider dose reduction; Child-Pugh Class C: contraindicated. |
| Pediatric use | 6-12 weeks: 4 mg/kg trimethoprim/20 mg/kg sulfamethoxazole orally every 12 hours; >12 weeks: 4-6 mg/kg trimethoprim/20-30 mg/kg sulfamethoxazole orally every 12 hours; maximum single dose 160 mg trimethoprim/800 mg sulfamethoxazole. |
| Geriatric use | Start at lower end of dosing range; monitor renal function and potassium levels; adjust dose based on CrCl; avoid in those with folate deficiency. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULFATRIM-DS (SULFATRIM-DS).
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted in breast milk. Milk-to-plasma ratio is approximately 0.5 for both. Risk of kernicterus in infants with G6PD deficiency or hyperbilirubinemia. Avoid in breastfeeding unless no alternative; monitor infant for jaundice, hemolysis, and diarrhea. |
| Teratogenic Risk | Sulfatrim-DS contains sulfamethoxazole and trimethoprim. In first trimester, sulfonamides cross placenta and may cause kernicterus due to bilirubin displacement; also associated with increased risk of neural tube defects (OR 2.7). In second and third trimesters, risk of kernicterus persists; trimethoprim is a folate antagonist, increasing risk of neural tube defects, cardiovascular malformations, and cleft lip/palate. Contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and fulminant hepatic necrosis have occurred. Discontinue at first sign of rash or any adverse reaction.
| Serious Effects |
Hypersensitivity to sulfonamides or trimethoprim, megaloblastic anemia due to folate deficiency, severe hepatic or renal impairment (CrCl <15 mL/min), pregnancy (especially first trimester and near term), lactation, infants <2 months of age, concurrent use with dofetilide.
| Precautions | Severe hypersensitivity reactions, hematologic toxicity (including agranulocytosis, aplastic anemia), hemolytic anemia in G6PD deficiency, hyperkalemia, acute renal injury, photosensitivity, risk of kernicterus in neonates, hepatic necrosis, electrolyte disturbances, increased risk of hypoglycemia with sulfonylureas, and potential for Clostridioides difficile infection. |
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| Fetal Monitoring | Maternal: Complete blood count (CBC), renal function, liver function tests, bilirubin levels, and signs of hypersensitivity. Fetal: Serial ultrasounds for congenital anomalies if exposed in first trimester; monitor for neonatal hyperbilirubinemia and hemolysis if exposed near term. |
| Fertility Effects | Trimethoprim may inhibit dihydrofolate reductase, potentially affecting gametogenesis. Animal studies show impaired fertility and increased preimplantation loss. Human data limited; advise caution in women attempting conception. |