SEPTRA DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).

How it works

SEPTRA DS is a combination of trimethoprim and sulfamethoxazole. Trimethoprim inhibits bacterial dihydrofolate reductase, while sulfamethoxazole inhibits dihydropteroate synthase, sequentially blocking folate synthesis and ultimately DNA synthesis in susceptible bacteria.

What the body does with it

Metabolism	Trimethoprim is metabolized in the liver to inactive metabolites via oxidative and conjugative pathways. Sulfamethoxazole is metabolized primarily via acetylation and glucuronidation in the liver.
Excretion	Renal excretion of unchanged drugs accounts for 50-70% of trimethoprim and 20-30% of sulfamethoxazole; biliary excretion is minor (<10% total).
Half-life	Trimethoprim: 8-10 hours; sulfamethoxazole: 10-12 hours (prolonged in renal impairment, e.g., creatinine clearance <30 mL/min increases half-life to >20 hours).
Protein binding	Trimethoprim: 42-46% (bound to albumin); sulfamethoxazole: 68-70% (primarily albumin).
Volume of Distribution	Trimethoprim: 1.3-1.8 L/kg (extensive tissue distribution, up to 2.0 L/kg in neonates); sulfamethoxazole: 0.21-0.36 L/kg (primarily extracellular fluid).
Bioavailability	Oral (tablet or suspension): 90-100% for both components.
Onset of Action	Oral: 1-4 hours (peak plasma concentrations); intravenous: within 30 minutes.
Duration of Action	Approximately 12 hours (dosing interval is every 12 hours); clinical effect persists for the dosing interval with steady-state achieved in 2-3 days.

Classification & Brands

Dosing & administration

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

Dosage form	TABLET
Renal impairment	CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: one-half usual dose; CrCl <15 mL/min: contraindicated.
Liver impairment	No specific Child-Pugh based dosing guidelines; use caution in severe hepatic impairment.
Pediatric use	8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole orally in two divided doses every 12 hours.
Geriatric use	May require dose reduction due to age-related renal impairment; monitor renal function and potassium levels.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).

Breastfeeding	Both trimethoprim and sulfamethoxazole are excreted in breast milk. M/P ratio approximately 1.0 for each. Theoretical risk of kernicterus and hemolytic anemia in G6PD-deficient infants. Caution recommended; monitor infant for jaundice, hemolysis, and hypersensitivity.
Teratogenic Risk	First trimester: Folate antagonism increases risk of neural tube defects, cardiovascular malformations, and oral clefts. Second and third trimesters: Risk of kernicterus in neonates due to bilirubin displacement; potential for hemolytic anemia in G6PD-deficient fetuses. Avoid use during pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: FATALITIES ASSOCIATED WITH SEVERE ADVERSE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, AND OTHER BLOOD DYSCRASIAS. SULFONAMIDES HAVE CAUSED HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS AND RESPIRATORY DISTRESS. USE WITH CAUTION IN PATIENTS WITH G6PD DEFICIENCY, PORPHYRIA, OR THYROID DYSFUNCTION.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfonamides, trimethoprim, or any component","Megaloblastic anemia due to folate deficiency","Severe hepatic or renal impairment (CrCl <15 mL/min)","Pregnancy at term or breastfeeding (potential for kernicterus in neonates)","Concurrent use with dofetilide (increased QT prolongation risk)","Infants <2 months of age (risk of kernicterus)"]

Clinical Precautions

Precautions

["Severe hypersensitivity reactions including SJS/TEN","Hematologic toxicity (agranulocytosis, aplastic anemia)","Hepatic necrosis","Renal toxicity (crystalluria, tubular necrosis)","Hyperkalemia (especially in elderly, renal impairment, or high doses)","Hypoglycemia (especially in malnourished or renal impairment)","Photosensitivity","Use in G6PD deficiency may cause hemolytic anemia"]

Clinical Tips & Counseling

Drug interactions

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SEPTRA DS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).

How it works

What the body does with it

Metabolism	Trimethoprim is metabolized in the liver to inactive metabolites via oxidative and conjugative pathways. Sulfamethoxazole is metabolized primarily via acetylation and glucuronidation in the liver.
Excretion	Renal excretion of unchanged drugs accounts for 50-70% of trimethoprim and 20-30% of sulfamethoxazole; biliary excretion is minor (<10% total).
Half-life	Trimethoprim: 8-10 hours; sulfamethoxazole: 10-12 hours (prolonged in renal impairment, e.g., creatinine clearance <30 mL/min increases half-life to >20 hours).
Protein binding	Trimethoprim: 42-46% (bound to albumin); sulfamethoxazole: 68-70% (primarily albumin).
Volume of Distribution	Trimethoprim: 1.3-1.8 L/kg (extensive tissue distribution, up to 2.0 L/kg in neonates); sulfamethoxazole: 0.21-0.36 L/kg (primarily extracellular fluid).
Bioavailability	Oral (tablet or suspension): 90-100% for both components.
Onset of Action	Oral: 1-4 hours (peak plasma concentrations); intravenous: within 30 minutes.
Duration of Action	Approximately 12 hours (dosing interval is every 12 hours); clinical effect persists for the dosing interval with steady-state achieved in 2-3 days.

Classification & Brands

Dosing & administration

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

Dosage form	TABLET
Renal impairment	CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: one-half usual dose; CrCl <15 mL/min: contraindicated.
Liver impairment	No specific Child-Pugh based dosing guidelines; use caution in severe hepatic impairment.
Pediatric use	8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole orally in two divided doses every 12 hours.
Geriatric use	May require dose reduction due to age-related renal impairment; monitor renal function and potassium levels.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).

Breastfeeding	Both trimethoprim and sulfamethoxazole are excreted in breast milk. M/P ratio approximately 1.0 for each. Theoretical risk of kernicterus and hemolytic anemia in G6PD-deficient infants. Caution recommended; monitor infant for jaundice, hemolysis, and hypersensitivity.
Teratogenic Risk	First trimester: Folate antagonism increases risk of neural tube defects, cardiovascular malformations, and oral clefts. Second and third trimesters: Risk of kernicterus in neonates due to bilirubin displacement; potential for hemolytic anemia in G6PD-deficient fetuses. Avoid use during pregnancy unless benefit outweighs risk.