SULFATRIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).

How it works

Sulfatrim is a combination of sulfamethoxazole, a dihydropteroate synthase inhibitor that blocks folate synthesis, and trimethoprim, a dihydrofolate reductase inhibitor that blocks reduction of dihydrofolate to tetrahydrofolate, resulting in sequential inhibition of bacterial folate metabolism.

What the body does with it

Metabolism	Sulfamethoxazole is metabolized via acetylation and glucuronidation; trimethoprim is metabolized via O-demethylation and oxidation. Both are substrates of CYP450 isoenzymes (e.g., CYP2C9 for sulfamethoxazole).
Excretion	Renal (70-80% as unchanged sulfamethoxazole and N4-acetylated metabolite; 30-40% as unchanged trimethoprim), biliary/fecal (20-30% sulfamethoxazole; 10-20% trimethoprim)
Half-life	Sulfamethoxazole: 9-11 hours (prolonged in renal impairment, e.g., up to 30 hours in severe renal failure). Trimethoprim: 8-10 hours (prolonged in hepatic impairment).
Protein binding	Sulfamethoxazole: 65-70% bound to albumin. Trimethoprim: 42-46% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Sulfamethoxazole: 0.15-0.28 L/kg (distributes well to tissues, including CSF). Trimethoprim: 1.3-1.8 L/kg (higher Vd indicates extensive tissue penetration).
Bioavailability	Oral: >90% for both components. IV: 100%.
Onset of Action	Oral: Onset within 1-2 hours for peak serum levels; clinical effect within 24-48 hours. IV: Onset within 30-60 minutes for peak serum levels.
Duration of Action	Oral/IV: Duration of antibacterial effect approximately 12 hours; dosing interval typically every 12 hours.

Classification & Brands

Brand Substitutes

Panam Suspension, Nolapse Suspension, Estrim Suspension, Salgatran Suspension, Hanprim Suspension, Cortina DS 800mg/160mg Tablet, Colizole DS 800mg/160mg Tablet, Tabrol DS Tablet, Trisulfose DS 800mg/160mg Tablet, Sepmax DS Tablet

Dosing & administration

160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 10-14 days.

Dosage form	SUSPENSION
Renal impairment	CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: reduce dose by 50% (e.g., 1 DS tablet every 24 hours). CrCl <15 mL/min: contraindicated (except for Pneumocystis jirovecii pneumonia prophylaxis where dosing is adjusted per protocol).
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: use with caution, consider monitoring liver enzymes. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity and altered metabolism.
Pediatric use	Based on trimethoprim component: 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole divided every 12 hours. For urinary tract infection: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. Maximum daily dose: 320 mg trimethoprim/1600 mg sulfamethoxazole.
Geriatric use	Start at lowest effective dose (e.g., 1 SS tablet [80 mg trimethoprim/400 mg sulfamethoxazole] every 12 hours). Monitor renal function (CrCl) closely; adjust dose per renal adjustment. Increased risk of hyperkalemia (especially with NSAIDs, ACE inhibitors) and sulfonamide hypersensitivity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).

Breastfeeding	Excreted into breast milk in low amounts (M/P ratio ~0.5-0.8). Use caution in infants with G6PD deficiency or hyperbilirubinemia; generally considered compatible but monitor for diarrhea, rash, or kernicterus.
Teratogenic Risk	First trimester: Avoid due to folate antagonism; risk of neural tube defects, cardiovascular malformations, and cleft lip/palate. Second/third trimester: Potential risk of kernicterus in neonates from sulfonamide displacement of bilirubin; avoid near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis; increased risk of kernicterus in neonates (avoid use in infants <2 months); caution in folate-deficient patients (elderly, alcoholics, anticonvulsant users).

Side Effect Profile

Serious Effects

Absolute Contraindications

History of sulfonamide hypersensitivity; megaloblastic anemia due to folate deficiency; infants <2 months; marked hepatic damage; severe renal insufficiency (CrCl <15 mL/min); concurrent use with dofetilide.

Clinical Precautions

Precautions

Hypersensitivity and severe skin reactions; hemolytic anemia in G6PD deficiency; hematopoietic toxicity (megaloblastic anemia); electrolyte disturbances (hyperkalemia with high doses); photosensitivity; caution in hepatic/renal impairment; pregnancy (risk of kernicterus); lactation (use with caution).

Clinical Tips & Counseling

Drug interactions

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SULFATRIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).

How it works

What the body does with it

Metabolism	Sulfamethoxazole is metabolized via acetylation and glucuronidation; trimethoprim is metabolized via O-demethylation and oxidation. Both are substrates of CYP450 isoenzymes (e.g., CYP2C9 for sulfamethoxazole).
Excretion	Renal (70-80% as unchanged sulfamethoxazole and N4-acetylated metabolite; 30-40% as unchanged trimethoprim), biliary/fecal (20-30% sulfamethoxazole; 10-20% trimethoprim)
Half-life	Sulfamethoxazole: 9-11 hours (prolonged in renal impairment, e.g., up to 30 hours in severe renal failure). Trimethoprim: 8-10 hours (prolonged in hepatic impairment).
Protein binding	Sulfamethoxazole: 65-70% bound to albumin. Trimethoprim: 42-46% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Sulfamethoxazole: 0.15-0.28 L/kg (distributes well to tissues, including CSF). Trimethoprim: 1.3-1.8 L/kg (higher Vd indicates extensive tissue penetration).
Bioavailability	Oral: >90% for both components. IV: 100%.
Onset of Action	Oral: Onset within 1-2 hours for peak serum levels; clinical effect within 24-48 hours. IV: Onset within 30-60 minutes for peak serum levels.
Duration of Action	Oral/IV: Duration of antibacterial effect approximately 12 hours; dosing interval typically every 12 hours.

Classification & Brands

Brand Substitutes

Dosing & administration

160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 10-14 days.

Dosage form	SUSPENSION
Renal impairment	CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: reduce dose by 50% (e.g., 1 DS tablet every 24 hours). CrCl <15 mL/min: contraindicated (except for Pneumocystis jirovecii pneumonia prophylaxis where dosing is adjusted per protocol).
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: use with caution, consider monitoring liver enzymes. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity and altered metabolism.
Pediatric use	Based on trimethoprim component: 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole divided every 12 hours. For urinary tract infection: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. Maximum daily dose: 320 mg trimethoprim/1600 mg sulfamethoxazole.
Geriatric use	Start at lowest effective dose (e.g., 1 SS tablet [80 mg trimethoprim/400 mg sulfamethoxazole] every 12 hours). Monitor renal function (CrCl) closely; adjust dose per renal adjustment. Increased risk of hyperkalemia (especially with NSAIDs, ACE inhibitors) and sulfonamide hypersensitivity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).

Breastfeeding	Excreted into breast milk in low amounts (M/P ratio ~0.5-0.8). Use caution in infants with G6PD deficiency or hyperbilirubinemia; generally considered compatible but monitor for diarrhea, rash, or kernicterus.
Teratogenic Risk	First trimester: Avoid due to folate antagonism; risk of neural tube defects, cardiovascular malformations, and cleft lip/palate. Second/third trimester: Potential risk of kernicterus in neonates from sulfonamide displacement of bilirubin; avoid near term.
Fetal Monitoring