Comparative Pharmacology
Head-to-head clinical analysis: SULFATRIM PEDIATRIC versus SULFATRIM DS.
Peer-Reviewed Evidence
Head-to-head clinical analysis: SULFATRIM PEDIATRIC versus SULFATRIM DS.
SULFATRIM PEDIATRIC vs SULFATRIM-DS
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Sulfamethoxazole inhibits dihydropteroate synthase, blocking bacterial folic acid synthesis; trimethoprim inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. Sequential blockade leads to bactericidal activity.
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.
Treatment of urinary tract infectionsAcute otitis mediaAcute exacerbations of chronic bronchitisTraveler's diarrheaPneumocystis jirovecii pneumonia (PCP) treatment and prophylaxisToxoplasmosis (off-label)Nocardiosis (off-label)
Urinary tract infectionsAcute otitis mediaAcute exacerbations of chronic bronchitisTraveler's diarrheaPneumocystis jirovecii pneumonia (treatment and prophylaxis)Toxoplasmosis (prophylaxis in immunocompromised)NocardiosisStenotrophomonas maltophilia infections
Sulfatrim Pediatric suspension contains sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL. For patients >40 kg, dose is 800 mg SMX/160 mg TMP orally every 12 hours for 10-14 days.
One double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) orally every 12 hours.
None Documented
None Documented
Sulfamethoxazole: 9-11 hours; Trimethoprim: 8-10 hours; prolonged in renal impairment (e.g., CrCl <30 mL/min).
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).
Sulfamethoxazole is metabolized primarily by acetylation (N-acetyltransferase) and glucuronidation; trimethoprim undergoes O-demethylation, N-oxidation, and conjugation. Both are metabolized in the liver.
Sulfamethoxazole is primarily metabolized via N-acetylation and glucuronidation; trimethoprim is metabolized by oxidation (CYP3A4) and conjugation.
Renal: 50-70% of total sulfamethoxazole (SMX) and 30-50% of total trimethoprim (TMP) are excreted unchanged in urine; the remainder as metabolites; biliary/fecal excretion is minimal.
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%.
Sulfamethoxazole: ~70% bound to albumin; Trimethoprim: ~44% bound to albumin.
SMX: ~70% bound to albumin; TMP: ~44% bound to albumin.
Sulfamethoxazole: Vd ~0.21 L/kg; Trimethoprim: Vd ~1.4 L/kg (higher tissue penetration).
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.
Oral: ~100% for both SMX and TMP.
Oral: 90-100% for both components (well absorbed from GI tract); IV: 100%.
CrCl 15-30 mL/min: same dose but increase interval to every 24 hours. CrCl <15 mL/min: not recommended.
CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: 50% of usual dose every 12 hours; CrCl <15 mL/min: not recommended.
Child-Pugh A: no adjustment. Child-Pugh B or C: use with caution, no specific dose guidelines; consider alternative therapy.
Child-Pugh Class A: no adjustment; Child-Pugh Class B: caution, consider dose reduction; Child-Pugh Class C: contraindicated.
Children >2 months: dose based on TMP component at 8 mg/kg/day divided every 12 hours (e.g., for 10 kg child: 80 mg TMP/day = 40 mg TMP every 12 hours, equivalent to 5 mL suspension every 12 hours). Maximum 160 mg TMP every 12 hours.
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.
Elderly may have reduced renal function; dose adjustment based on creatinine clearance (see renal_adjustment). Monitor for hypersensitivity and renal function. Avoid in those with folic acid deficiency.
Start at lower end of dosing range; monitor renal function and potassium levels; adjust dose based on CrCl; avoid in those with folate deficiency.
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis; hemolytic anemia in G6PD deficiency; kernicterus in neonates; contraindicated in pregnancy at term and nursing mothers.
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.
Monitor for severe skin reactions, hepatic injury, hematologic toxicity (including agranulocytosis, aplastic anemia), electrolyte disturbances (hyperkalemia with high-dose trimethoprim), hypersensitivity reactions, and photosensitivity. Use with caution in folate deficiency, impaired hepatic/renal function, and elderly.
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.
Hypersensitivity to sulfonamides or trimethoprim; marked hepatic damage; severe renal insufficiency without monitoring; megaloblastic anemia due to folate deficiency; pregnancy (especially near term); nursing mothers; neonates (especially premature) due to risk of kernicterus.
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.
Data Pending Review
Data Pending Review
Avoid potassium-rich foods (e.g., bananas, oranges, potatoes) and high-potassium salt substitutes as trimethoprim can increase serum potassium. Alcohol may cause disulfiram-like reaction (rare).
Avoid alcohol as it may cause a disulfiram-like reaction. High potassium foods (e.g., bananas, oranges, potatoes) should be consumed cautiously due to risk of hyperkalemia. Ensure adequate hydration but do not restrict fluids.
Pregnancy Category D. First trimester: Associated with increased risk of neural tube defects, cardiovascular malformations, and oral clefts due to folate antagonism. Second and third trimesters: Risk of kernicterus in the neonate due to bilirubin displacement from albumin; avoid use near term.
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.
Compatible with caution. Sulfamethoxazole and trimethoprim are excreted into breast milk. M/P ratio not well established; concentrations are low but may cause hemolysis in G6PD-deficient infants or interfere with folate metabolism. Avoid in premature or ill infants.
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.
No standard dose adjustment required, but increased renal clearance in pregnancy may reduce serum levels; monitor clinical response. Caution in folate deficiency; consider folate supplementation.
Pregnancy increases renal clearance (by 30-50%) and volume of distribution, potentially reducing serum levels. Monitor therapeutic efficacy; consider dose adjustments based on clinical response and drug levels. Avoid use in pregnancy unless necessary; if used, consider increased dose or alternative.
Category C
Category C
SULFATRIM PEDIATRIC contains sulfamethoxazole and trimethoprim (co-trimoxazole). Use with caution in infants <2 months due to risk of kernicterus from sulfonamide displacement of bilirubin. Monitor for hypersensitivity reactions (Stevens-Johnson syndrome). Adjust dose in renal impairment (CrCl <30 mL/min contraindicated). Avoid in G6PD deficiency due to hemolytic anemia risk. Ensure adequate hydration to prevent crystalluria.
Sulfatrim-DS is a fixed-dose combination of sulfamethoxazole and trimethoprim (co-trimoxazole). It is bacteriostatic and requires adequate folic acid synthesis inhibition; avoid concurrent use with methotrexate. Monitor renal function and potassium levels; hyperkalemia can occur, especially in elderly or those with renal impairment. Use with caution in G6PD deficiency due to risk of hemolytic anemia. For PCP prophylaxis, dosing frequency is typically three times weekly.
Take with a full glass of water and stay well-hydrated to prevent kidney stones.Complete the full course even if symptoms improve.Avoid prolonged sun exposure; use sunscreen as this drug increases photosensitivity.Report any rash, sore throat, fever, or unusual bleeding immediately.Shake suspension well before measuring dose.
Take with a full glass of water to prevent crystalluria.Complete the full course of therapy even if you feel better.Avoid prolonged sun exposure; use sunscreen as this medication increases sun sensitivity.Report immediately if you develop rash, sore throat, fever, or unusual bruising/bleeding.Do not take if you are pregnant, especially in the third trimester, or breastfeeding.