SULFAMETHOPRIM-DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFAMETHOPRIM-DS (SULFAMETHOPRIM-DS).

How it works

Sulfamethoprim-DS is a combination of sulfamethoxazole, a dihydropteroate synthase inhibitor, and trimethoprim, a dihydrofolate reductase inhibitor. The sequential inhibition of folate synthesis leads to bactericidal activity.

What the body does with it

Metabolism	Sulfamethoxazole undergoes hepatic metabolism via N-acetylation and glucuronidation; trimethoprim is metabolized primarily via hepatic oxidation (CYP450) and conjugation.
Excretion	Renal excretion of unchanged drug (50-70%) and metabolites (primarily N4-acetylated form, 15-30%); biliary/fecal excretion accounts for <5%.
Half-life	Terminal elimination half-life of sulfamethoxazole is 9-11 hours (prolonged to 20-50 hours in severe renal impairment). Clinically, this supports twice-daily dosing in normal renal function; dose adjustment required for CrCl <30 mL/min.
Protein binding	Sulfamethoxazole: ~65-70% bound primarily to albumin. N4-acetyl metabolite: ~90% bound.
Volume of Distribution	Vd: 0.21-0.36 L/kg (sulfamethoxazole). Distributes widely into tissues, including CSF (30-50% of serum concentration), sputum, and middle ear fluid.
Bioavailability	Oral: 85-90% (well absorbed).
Onset of Action	Oral: 1-4 hours (time to peak serum concentration); peak antibacterial effect correlates with serum levels above MIC, achieved within 1-2 doses.
Duration of Action	Duration of therapeutic serum concentrations: 8-12 hours (oral) based on dosing interval of 12 hours. Continuous coverage maintained with twice-daily administration.

Classification & Brands

Dosing & administration

Sulfamethoprim-DS (trimethoprim 160 mg-sulfamethoxazole 800 mg) orally every 12 hours for 10-14 days for uncomplicated UTI; for Pneumocystis jirovecii pneumonia: 3-5 mg/kg/day (based on TMP) orally or IV divided every 6-8 hours for 21 days.

Dosage form	TABLET
Renal impairment	CrCl 15-30 mL/min: reduce dose by 50% and administer every 12 hours (standard dose every 24 hours alternative). CrCl <15 mL/min: contraindicated except for PCP where dosing interval extended to 24-48 hours with monitoring.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: caution, no specific guidelines; Child-Pugh C: avoid due to potential for accumulation and hepatotoxicity.
Pediatric use	Based on TMP 4-6 mg/kg/day orally divided every 12 hours for UTI; for PCP: TMP 15-20 mg/kg/day IV/orally divided every 6-8 hours. Use adjusted body weight for obese children.
Geriatric use	Caution due to increased risk of hyperkalemia, renal impairment, and drug interactions (e.g., ACE inhibitors, ARBs). Start with weight-based dosing (TMP 4-5 mg/kg/day) and monitor renal function and serum potassium.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULFAMETHOPRIM-DS (SULFAMETHOPRIM-DS).

Breastfeeding	Excreted into breast milk (M/P ratio approximately 0.6). Risk to nursing infant if G6PD deficient (hemolysis) or ill/late preterm. Use with caution; American Academy of Pediatrics considers compatible if infant is healthy.
Teratogenic Risk	FDA Category D: First trimester exposure associated with neural tube defects, cardiovascular malformations, and oral clefts due to folate antagonism. Second and third trimester: increased risk of kernicterus in neonates due to bilirubin displacement; avoid near term (after 36 weeks).

Warnings & precautions

■ FDA Black Box Warning

Warning: Fatalities associated with sulfonamide hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia) have been reported.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to sulfonamides or trimethoprim, megaloblastic anemia due to folate deficiency, severe hepatic or renal impairment (if not dose-adjusted), concomitant use with dofetilide, and use in infants <2 months of age.

Clinical Precautions

Precautions

Hypersensitivity reactions, hematologic toxicity (monitor CBC), renal impairment (dose adjustment), hyperkalemia (especially with high doses), folate deficiency (prolonged use), phototoxicity, and potential for kernicterus in neonates. Avoid use in pregnancy at term and in infants <2 months.

Clinical Tips & Counseling

Drug interactions

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SULFAMETHOPRIM-DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFAMETHOPRIM-DS (SULFAMETHOPRIM-DS).

How it works

What the body does with it

Metabolism	Sulfamethoxazole undergoes hepatic metabolism via N-acetylation and glucuronidation; trimethoprim is metabolized primarily via hepatic oxidation (CYP450) and conjugation.
Excretion	Renal excretion of unchanged drug (50-70%) and metabolites (primarily N4-acetylated form, 15-30%); biliary/fecal excretion accounts for <5%.
Half-life	Terminal elimination half-life of sulfamethoxazole is 9-11 hours (prolonged to 20-50 hours in severe renal impairment). Clinically, this supports twice-daily dosing in normal renal function; dose adjustment required for CrCl <30 mL/min.
Protein binding	Sulfamethoxazole: ~65-70% bound primarily to albumin. N4-acetyl metabolite: ~90% bound.
Volume of Distribution	Vd: 0.21-0.36 L/kg (sulfamethoxazole). Distributes widely into tissues, including CSF (30-50% of serum concentration), sputum, and middle ear fluid.
Bioavailability	Oral: 85-90% (well absorbed).
Onset of Action	Oral: 1-4 hours (time to peak serum concentration); peak antibacterial effect correlates with serum levels above MIC, achieved within 1-2 doses.
Duration of Action	Duration of therapeutic serum concentrations: 8-12 hours (oral) based on dosing interval of 12 hours. Continuous coverage maintained with twice-daily administration.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	CrCl 15-30 mL/min: reduce dose by 50% and administer every 12 hours (standard dose every 24 hours alternative). CrCl <15 mL/min: contraindicated except for PCP where dosing interval extended to 24-48 hours with monitoring.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: caution, no specific guidelines; Child-Pugh C: avoid due to potential for accumulation and hepatotoxicity.
Pediatric use	Based on TMP 4-6 mg/kg/day orally divided every 12 hours for UTI; for PCP: TMP 15-20 mg/kg/day IV/orally divided every 6-8 hours. Use adjusted body weight for obese children.
Geriatric use	Caution due to increased risk of hyperkalemia, renal impairment, and drug interactions (e.g., ACE inhibitors, ARBs). Start with weight-based dosing (TMP 4-5 mg/kg/day) and monitor renal function and serum potassium.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULFAMETHOPRIM-DS (SULFAMETHOPRIM-DS).

Breastfeeding	Excreted into breast milk (M/P ratio approximately 0.6). Risk to nursing infant if G6PD deficient (hemolysis) or ill/late preterm. Use with caution; American Academy of Pediatrics considers compatible if infant is healthy.
Teratogenic Risk	FDA Category D: First trimester exposure associated with neural tube defects, cardiovascular malformations, and oral clefts due to folate antagonism. Second and third trimester: increased risk of kernicterus in neonates due to bilirubin displacement; avoid near term (after 36 weeks).