TRIPLE SULFA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).

How it works

Inhibits bacterial dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), blocking folate synthesis essential for nucleic acid production.

What the body does with it

Metabolism	Sulfamethoxazole: primarily via N-acetylation and glucuronidation; Trimethoprim: hepatic metabolism via oxidation and conjugation (CYP450 minimal involvement).
Excretion	80-90% renal (glomerular filtration and tubular secretion) as unchanged drug and acetylated metabolites; 5-10% biliary/fecal.
Half-life	6-12 hours (sulfadiazine 10-13h, sulfamerazine 16-24h, sulfamethazine 7-12h); prolonged in renal impairment.
Protein binding	50-70% bound to albumin (sulfadiazine ~55%, sulfamerazine ~65%, sulfamethazine ~50%).
Volume of Distribution	0.5-0.8 L/kg (distributes widely including CSF, pleural, peritoneal fluids).
Bioavailability	Oral: 80-100% (well absorbed from GI tract); IV: 100%.
Onset of Action	Oral: 1-4 hours; IV: immediate (minutes).
Duration of Action	12-24 hours (depends on renal function and acetylator status); maintain therapeutic levels for 7-10 days.

Classification & Brands

Dosing & administration

1 g orally every 12 hours for 10 days (as sulfadiazine, sulfamethazine, and sulfamerazine combination).

Dosage form	TABLET
Renal impairment	CrCl 30-50 mL/min: 1 g every 24 hours; CrCl 10-29 mL/min: 1 g every 48 hours; CrCl <10 mL/min: Not recommended.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	2 months or older: 50-60 mg/kg/day divided every 12 hours; maximum 3 g/day.
Geriatric use	Use with caution, monitor renal function; reduce dose as per renal adjustment; increase fluid intake to prevent crystalluria.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).

Breastfeeding	Sulfonamides are excreted into breast milk in small amounts; M/P ratio not well established. Theoretical risk of kernicterus in nursing infants, especially those with G6PD deficiency or jaundice. Contraindicated in nursing mothers of premature or ill infants, or those with hyperbilirubinemia. Use with caution otherwise.
Teratogenic Risk	First trimester: sulfonamides are associated with a small increased risk of neural tube defects, cardiovascular malformations, and oral clefts based on some studies; however, the absolute risk is low. Second and third trimesters: risk of kernicterus in the newborn due to displacement of bilirubin from albumin, especially near term. Avoid use in third trimester.

Warnings & precautions

■ FDA Black Box Warning

Fatalities associated with sulfonamide hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Contraindicated in patients with a history of sulfonamide hypersensitivity.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of sulfonamide hypersensitivity, severe hepatic damage, porphyria, megaloblastic anemia due to folate deficiency, infants <2 months (except for congenital toxoplasmosis), marked renal impairment (CrCl <15 mL/min) unless dialysis available, significant leucopenia/pancytopenia, concomitant dofetilide (increased QT).

Clinical Precautions

Precautions

Severe hypersensitivity reactions (SJS/TEN), hematologic toxicity (monitor CBC), hepatotoxicity, renal impairment (adjust dose), hypoglycemia in elderly/non-insulin-dependent diabetes, kernicterus in neonates, caution with G6PD deficiency (hemolysis), advanced age, concomitant warfarin/phenytoin.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

TRIPLE SULFA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).

How it works

Inhibits bacterial dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), blocking folate synthesis essential for nucleic acid production.

What the body does with it

Metabolism	Sulfamethoxazole: primarily via N-acetylation and glucuronidation; Trimethoprim: hepatic metabolism via oxidation and conjugation (CYP450 minimal involvement).
Excretion	80-90% renal (glomerular filtration and tubular secretion) as unchanged drug and acetylated metabolites; 5-10% biliary/fecal.
Half-life	6-12 hours (sulfadiazine 10-13h, sulfamerazine 16-24h, sulfamethazine 7-12h); prolonged in renal impairment.
Protein binding	50-70% bound to albumin (sulfadiazine ~55%, sulfamerazine ~65%, sulfamethazine ~50%).
Volume of Distribution	0.5-0.8 L/kg (distributes widely including CSF, pleural, peritoneal fluids).
Bioavailability	Oral: 80-100% (well absorbed from GI tract); IV: 100%.
Onset of Action	Oral: 1-4 hours; IV: immediate (minutes).
Duration of Action	12-24 hours (depends on renal function and acetylator status); maintain therapeutic levels for 7-10 days.

Classification & Brands

Dosing & administration

1 g orally every 12 hours for 10 days (as sulfadiazine, sulfamethazine, and sulfamerazine combination).

Dosage form	TABLET
Renal impairment	CrCl 30-50 mL/min: 1 g every 24 hours; CrCl 10-29 mL/min: 1 g every 48 hours; CrCl <10 mL/min: Not recommended.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	2 months or older: 50-60 mg/kg/day divided every 12 hours; maximum 3 g/day.
Geriatric use	Use with caution, monitor renal function; reduce dose as per renal adjustment; increase fluid intake to prevent crystalluria.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).

Breastfeeding	Sulfonamides are excreted into breast milk in small amounts; M/P ratio not well established. Theoretical risk of kernicterus in nursing infants, especially those with G6PD deficiency or jaundice. Contraindicated in nursing mothers of premature or ill infants, or those with hyperbilirubinemia. Use with caution otherwise.
Teratogenic Risk	First trimester: sulfonamides are associated with a small increased risk of neural tube defects, cardiovascular malformations, and oral clefts based on some studies; however, the absolute risk is low. Second and third trimesters: risk of kernicterus in the newborn due to displacement of bilirubin from albumin, especially near term. Avoid use in third trimester.