SULFISOXAZOLE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).

How it works

Sulfisoxazole is a sulfonamide antibiotic that inhibits bacterial dihydropteroate synthase, blocking the synthesis of dihydrofolic acid and ultimately inhibiting bacterial folate synthesis and DNA replication.

What the body does with it

Metabolism	Primarily metabolized in the liver via acetylation and glucuronidation; also undergoes N4-acetylation.
Excretion	Renal excretion accounts for 70-85% of elimination, predominantly as unchanged drug (30-50%) and the N4-acetyl metabolite (15-30%). Biliary/fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life is 5-7 hours in adults with normal renal function; prolonged to 12-20 hours in renal impairment (CrCl <30 mL/min).
Protein binding	50-60% bound to serum albumin.
Volume of Distribution	0.25-0.5 L/kg; distributes widely including CSF (30-80% of serum levels), pleural, and peritoneal fluids.
Bioavailability	Oral: 90-100% (well absorbed, but delayed by food). Intravenous: 100%.
Onset of Action	Oral: 1-2 hours after first dose; Intravenous: 30-60 minutes after infusion start.
Duration of Action	Duration is 6-12 hours for oral dosing, requiring dosing every 6 hours for continuous therapy. Renal impairment prolongs duration.

Classification & Brands

Dosing & administration

1-2 g orally once, then 500 mg-1 g orally every 4-6 hours; maximum 6 g/day.

Dosage form	TABLET
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: give q8-12h; CrCl <10 mL/min: give q12-24h.
Liver impairment	No specific recommendations; use caution in severe hepatic impairment.
Pediatric use	>2 months: initial dose 75 mg/kg, then 150 mg/kg/day divided q4-6h; maximum 6 g/day.
Geriatric use	Start at lower end of dosing range due to age-related renal decline; monitor renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).

Breastfeeding	Sulfisoxazole is excreted into breast milk. M/P ratio approximately 0.2-0.4. American Academy of Pediatrics considers compatible with breastfeeding, but caution is advised in premature infants or those with hyperbilirubinemia or G6PD deficiency.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Theoretical risk of teratogenicity due to folate antagonism; limited human data show no clear increase in major malformations. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; contraindicated near term (after 37 weeks) and during labor.

Warnings & precautions

■ FDA Black Box Warning

Fatalities have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfonamides or any component","Porphyria","Severe hepatic or renal impairment","Pregnancy at term and breastfeeding (risk of kernicterus)","Infants less than 2 months of age (except for congenital toxoplasmosis)"]

Clinical Precautions

Precautions

["Increased risk of severe hypersensitivity reactions, especially in patients with HIV or G6PD deficiency","Hematologic toxicity including agranulocytosis and aplastic anemia","Hepatic injury and hepatitis","Renal impairment and crystalluria","Photosensitivity and skin reactions","Use in pregnancy: risk of kernicterus in neonates; avoid near term","Sulfonamide cross-sensitivity"]

Clinical Tips & Counseling

Drug interactions

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SULFISOXAZOLE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).

How it works

What the body does with it

Metabolism	Primarily metabolized in the liver via acetylation and glucuronidation; also undergoes N4-acetylation.
Excretion	Renal excretion accounts for 70-85% of elimination, predominantly as unchanged drug (30-50%) and the N4-acetyl metabolite (15-30%). Biliary/fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life is 5-7 hours in adults with normal renal function; prolonged to 12-20 hours in renal impairment (CrCl <30 mL/min).
Protein binding	50-60% bound to serum albumin.
Volume of Distribution	0.25-0.5 L/kg; distributes widely including CSF (30-80% of serum levels), pleural, and peritoneal fluids.
Bioavailability	Oral: 90-100% (well absorbed, but delayed by food). Intravenous: 100%.
Onset of Action	Oral: 1-2 hours after first dose; Intravenous: 30-60 minutes after infusion start.
Duration of Action	Duration is 6-12 hours for oral dosing, requiring dosing every 6 hours for continuous therapy. Renal impairment prolongs duration.

Classification & Brands

Dosing & administration

1-2 g orally once, then 500 mg-1 g orally every 4-6 hours; maximum 6 g/day.

Dosage form	TABLET
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: give q8-12h; CrCl <10 mL/min: give q12-24h.
Liver impairment	No specific recommendations; use caution in severe hepatic impairment.
Pediatric use	>2 months: initial dose 75 mg/kg, then 150 mg/kg/day divided q4-6h; maximum 6 g/day.
Geriatric use	Start at lower end of dosing range due to age-related renal decline; monitor renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SULFISOXAZOLE (SULFISOXAZOLE).

Breastfeeding	Sulfisoxazole is excreted into breast milk. M/P ratio approximately 0.2-0.4. American Academy of Pediatrics considers compatible with breastfeeding, but caution is advised in premature infants or those with hyperbilirubinemia or G6PD deficiency.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Theoretical risk of teratogenicity due to folate antagonism; limited human data show no clear increase in major malformations. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; contraindicated near term (after 37 weeks) and during labor.