SEPTRA DS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).
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.
| 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. |
| Molecular Weight | Sulfamethoxazole: 253.28 Da; Trimethoprim: 290.3 Da |
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. |
| 1st trimester | Avoid in first trimester due to teratogenic risk (folate antagonism). Associated with neural tube defects, cardiovascular malformations. |
| 2nd trimester | Use only if clearly needed; may cause kernicterus in neonates if given near term due to displacement of bilirubin from albumin. |
| 3rd trimester | Avoid near term (after 36 weeks) due to risk of kernicterus and hemolytic anemia in neonates with G6PD deficiency. |
Clinical note
Comprehensive clinical and safety monograph for SEPTRA DS (SEPTRA DS).
| Placental transfer | Both components cross the placenta; sulfamethoxazole achieves fetal concentrations ~50-90% of maternal levels, trimethoprim ~30-60%. |
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into breast milk in low concentrations. Risk of kernicterus in infants <2 months old or with G6PD deficiency. Use with caution; alternative agents preferred during lactation. |
■ 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.
| Serious Effects |
Hypersensitivity to sulfonamides or trimethoprimMegaloblastic anemia due to folate deficiencySevere hepatic damageSevere renal dysfunction (CrCl <15 mL/min) unless monitoredInfants <2 months of age (except for treatment of congenital toxoplasmosis)
| 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 |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal complete blood count (CBC) for folate deficiency and myelosuppression; renal and hepatic function. In fetus, ultrasound for structural anomalies if first-trimester exposure. In neonate, monitor bilirubin and signs of kernicterus; G6PD status if indicated. |
| Fertility Effects | Reversible inhibition of spermatogenesis in males via folate antagonism; may impair female fertility by disrupting endometrial function. Clinical significance not fully established; discontinue if conception desired. |
| Avoid high-potassium foods (e.g., bananas, oranges, potatoes) unless medically advised, due to hyperkalemia risk. Folate-rich foods (e.g., green leafy vegetables) can be beneficial. Limit alcohol as it may increase side effects. |
| Clinical Pearls | SEPTRA DS contains sulfamethoxazole and trimethoprim. Use caution in elderly, renal impairment (CrCl <15 mL/min contraindicated), or with potassium-sparing diuretics due to hyperkalemia risk. Monitor for hypersensitivity, including Stevens-Johnson syndrome. Folic acid supplementation may reduce myelosuppression risk. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Complete full course even if symptoms improve. · Avoid sun exposure; use sunscreen as photosensitivity may occur. · Report rash, fever, sore throat, or unusual bruising immediately. · Do not take if pregnant or breastfeeding. |