SULFALAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).

How it works

Sulfamethoxazole is a sulfonamide that competitively inhibits dihydropteroate synthase, blocking folic acid synthesis; trimethoprim inhibits dihydrofolate reductase, producing sequential blockade of folic acid metabolism in bacteria.

What the body does with it

Metabolism	Sulfamethoxazole is metabolized via N-acetylation (N-acetyltransferase) and glucuronidation (UGT) in the liver. Trimethoprim undergoes O-demethylation (CYP3A4) and N-oxidation.
Excretion	Renal: approximately 70-80% as unchanged drug and acetylated metabolite; biliary/fecal: 20-30%
Half-life	Terminal elimination half-life: 7-12 hours (prolonged in renal impairment up to 24-48 hours; clinical context: dosing interval adjustment needed for CrCl <30 mL/min)
Protein binding	Approximately 50-70% bound to albumin; primary binding protein: albumin; also binds to alpha-1-acid glycoprotein (lesser extent)
Volume of Distribution	Vd: 0.5-0.8 L/kg; indicates moderate tissue distribution, primarily confined to extracellular fluid; clinical meaning: distribution consistent with limited intracellular penetration
Bioavailability	Oral: 85-95% (well absorbed; less than complete due to first-pass metabolism); Intramuscular: 100% (rapid and complete absorption)
Onset of Action	Oral: 2-4 hours (clinical effect: bacteriostatic activity); Intravenous: immediate (peak plasma concentration achieved by end of infusion)
Duration of Action	Oral: 12-24 hours (sufficient for twice-daily dosing; clinical note: sustained bacteriostatic effect); Intravenous: 12 hours (dosing every 12 hours recommended)

Classification & Brands

Dosing & administration

Oral: 500 mg to 1 g every 12 hours; extended-release: 1 g every 12 hours. Intravenous: 1 g every 12 hours.

Dosage form	TABLET
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 15-50 mL/min: 500 mg every 12 hours; CrCl <15 mL/min: 500 mg every 24 hours; hemodialysis: 500 mg every 24 hours plus dose after dialysis.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Oral: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose). Intravenous: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose).
Geriatric use	Start at low end of dosing range; monitor renal function and adjust based on CrCl.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).

Breastfeeding	Sulfamethoxazole is excreted into human breast milk with M/P ratio of approximately 0.04-0.1. Trimethoprim M/P ratio ~0.5-1.5. American Academy of Pediatrics considers compatible with breastfeeding, but caution in infants with G6PD deficiency, hyperbilirubinemia, or preterm infants due to risk of kernicterus and hemolysis.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Folate antagonist; case-control studies suggest increased risk of neural tube defects, cardiovascular malformations, and oral clefts. Second and third trimesters: Risk of kernicterus in neonates, hemolytic anemia in G6PD-deficient fetuses, and potential for neonatal hypoglycemia. Avoid in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Fatalities associated with sulfonamide hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia) have been reported. Reserve for susceptible infections when benefit outweighs risk.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to sulfonamides, trimethoprim, or any component; severe hepatic or renal impairment (CrCl <15 mL/min) not on dialysis; megaloblastic anemia due to folate deficiency; concurrent use with dofetilide; pregnancy (first trimester) and lactation (avoid in infants <2 months).

Clinical Precautions

Precautions

Hypersensitivity (life-threatening skin reactions, eosinophilia, drug fever); hematologic toxicity (thrombocytopenia, leukopenia); hepatotoxicity; renal toxicity (interstitial nephritis, crystalluria) with adequate hydration; electrolyte disturbances (hyperkalemia, hyponatremia); hemolysis in G6PD deficiency; increased INR with warfarin; hypoglycemia with sulfonylureas; photosensitivity; folate depletion (megaloblastic anemia) with prolonged use.

Clinical Tips & Counseling

Drug interactions

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SULFALAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).

How it works

What the body does with it

Metabolism	Sulfamethoxazole is metabolized via N-acetylation (N-acetyltransferase) and glucuronidation (UGT) in the liver. Trimethoprim undergoes O-demethylation (CYP3A4) and N-oxidation.
Excretion	Renal: approximately 70-80% as unchanged drug and acetylated metabolite; biliary/fecal: 20-30%
Half-life	Terminal elimination half-life: 7-12 hours (prolonged in renal impairment up to 24-48 hours; clinical context: dosing interval adjustment needed for CrCl <30 mL/min)
Protein binding	Approximately 50-70% bound to albumin; primary binding protein: albumin; also binds to alpha-1-acid glycoprotein (lesser extent)
Volume of Distribution	Vd: 0.5-0.8 L/kg; indicates moderate tissue distribution, primarily confined to extracellular fluid; clinical meaning: distribution consistent with limited intracellular penetration
Bioavailability	Oral: 85-95% (well absorbed; less than complete due to first-pass metabolism); Intramuscular: 100% (rapid and complete absorption)
Onset of Action	Oral: 2-4 hours (clinical effect: bacteriostatic activity); Intravenous: immediate (peak plasma concentration achieved by end of infusion)
Duration of Action	Oral: 12-24 hours (sufficient for twice-daily dosing; clinical note: sustained bacteriostatic effect); Intravenous: 12 hours (dosing every 12 hours recommended)

Classification & Brands

Dosing & administration

Oral: 500 mg to 1 g every 12 hours; extended-release: 1 g every 12 hours. Intravenous: 1 g every 12 hours.

Dosage form	TABLET
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 15-50 mL/min: 500 mg every 12 hours; CrCl <15 mL/min: 500 mg every 24 hours; hemodialysis: 500 mg every 24 hours plus dose after dialysis.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Oral: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose). Intravenous: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose).
Geriatric use	Start at low end of dosing range; monitor renal function and adjust based on CrCl.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).

Breastfeeding	Sulfamethoxazole is excreted into human breast milk with M/P ratio of approximately 0.04-0.1. Trimethoprim M/P ratio ~0.5-1.5. American Academy of Pediatrics considers compatible with breastfeeding, but caution in infants with G6PD deficiency, hyperbilirubinemia, or preterm infants due to risk of kernicterus and hemolysis.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Folate antagonist; case-control studies suggest increased risk of neural tube defects, cardiovascular malformations, and oral clefts. Second and third trimesters: Risk of kernicterus in neonates, hemolytic anemia in G6PD-deficient fetuses, and potential for neonatal hypoglycemia. Avoid in pregnancy unless benefit outweighs risk.