SEPTRA GRAPE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEPTRA GRAPE (SEPTRA GRAPE).
Septra Grape (trimethoprim/sulfamethoxazole) inhibits bacterial folic acid synthesis via sequential blockade: sulfamethoxazole inhibits dihydropteroate synthase, and trimethoprim inhibits dihydrofolate reductase, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is metabolized via N-acetylation and glucuronidation; trimethoprim is metabolized to oxide and hydroxylated metabolites. Both are primarily excreted renally. |
| Excretion | Renal: 50-70% unchanged (trimethoprim), 30-50% as N-acetyl metabolite; sulfamethoxazole: 70-80% as metabolites, 20-30% unchanged; biliary excretion minimal (<5% total). |
| Half-life | Trimethoprim: 8-10 hours (renal impairment >24h). Sulfamethoxazole: 10-13 hours (acetylation phenotype; prolonged in renal impairment). Clinical: Dosing interval generally 12h; adjust CrCl <30 mL/min. |
| Protein binding | Trimethoprim: 42-46% (primarily albumin). Sulfamethoxazole: 68-72% (albumin; decreased in uremia). |
| Volume of Distribution | Trimethoprim: 1.3-1.8 L/kg (widespread; high tissue penetration, including CNS). Sulfamethoxazole: 0.15-0.3 L/kg (predominantly extracellular). |
| Bioavailability | Oral: Trimethoprim 95-100%, sulfamethoxazole 85-95% (both well absorbed). IV: 100%. |
| Onset of Action | Oral: 1-4 hours (therapeutic levels achieved in 2-4h). IV: 1-2 hours (time to bactericidal concentrations). |
| Duration of Action | 12-24 hours; bacteriostatic activity persists ~12h due to dual folate inhibition. Clinical: Twice-daily dosing for most infections. |
| Molecular Weight | Trimethoprim: 290.32 Da; Sulfamethoxazole: 253.28 Da |
160 mg trimethoprim / 800 mg sulfamethoxazole (1 double-strength tablet) orally every 12 hours.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl 30-50 mL/min: reduce dose by 50% or extend interval to 24 hours. CrCl <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50% and monitor liver function. Child-Pugh Class C: contraindicated. |
| Pediatric use | 8 mg/kg/day trimethoprim / 40 mg/kg/day sulfamethoxazole in two divided doses orally every 12 hours. |
| Geriatric use | Use lower end of dosing range due to increased risk of adverse effects; monitor renal function and electrolytes; adjust dose if CrCl <50 mL/min. |
| 1st trimester | Coadministration of trimethoprim-sulfamethoxazole in the first trimester is associated with increased risk of neural tube defects, cardiovascular malformations, and urinary tract defects due to folate antagonism. Avoid use unless no alternative. |
| 2nd trimester | Use with caution; risk of kernicterus in the newborn if sulfonamide displaces bilirubin from albumin. Limited data suggest low risk but consider alternative agents. |
| 3rd trimester | Contraindicated in the third trimester due to risk of neonatal hemolysis, methemoglobinemia, and kernicterus from sulfamethoxazole and potential for trimethoprim-induced folate deficiency. |
Clinical note
Comprehensive clinical and safety monograph for SEPTRA GRAPE (SEPTRA GRAPE).
| Placental transfer | Both trimethoprim and sulfamethoxazole cross the placenta freely. Sulfamethoxazole reaches fetal serum levels 50-100% of maternal levels; trimethoprim levels are approximately 30-50%. |
| Breastfeeding |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.
| Serious Effects |
Hypersensitivity to trimethoprim or sulfonamidesMegaloblastic anemia due to folate deficiencyInfants <2 months of ageSevere hepatic damageSevere renal insufficiency (CrCl <15 mL/min)Porphyria (may precipitate acute attack)
| Precautions | Monitor for severe hypersensitivity reactions, hematologic toxicity (especially with folate deficiency), hemolysis in G6PD deficiency, hepatotoxicity, electrolyte disturbances (hyperkalemia with high-dose trimethoprim), and Clostridioides difficile-associated diarrhea. |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach) if elderly or on ARBs/ACE inhibitors due to hyperkalemia risk. No specific food restrictions; maintain adequate fluid intake to prevent kidney stones. Alcohol may cause disulfiram-like reaction (uncommon but possible). |
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| Trimethoprim and sulfamethoxazole are excreted into breast milk in low concentrations. The risk to a nursing infant is minimal, but caution is advised in infants with G6PD deficiency or hyperbilirubinemia. Monitor for rash, diarrhea, or jaundice. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | First trimester: Exposure associated with increased risk of neural tube defects (1.9-3.4% vs 0.5% baseline), cardiovascular malformations, and oral clefts due to folate antagonism. Second/third trimesters: Risk of kernicterus in neonates from sulfonamide displacement of bilirubin from albumin; avoid near term. Also associated with growth restriction and low birth weight. |
| Fetal Monitoring | Maternal: CBC with differential and platelets, renal function tests, liver function tests, serum folate levels if prolonged therapy. Fetal: Detailed anatomy ultrasound at 18-20 weeks to assess for neural tube defects; consider fetal echocardiography if first-trimester exposure. Monitor neonatal bilirubin levels if maternal use near term. |
| Fertility Effects | Trimethoprim may impair spermatogenesis in males via antifolate effects; reversible upon discontinuation. No known effect on female fertility. In women, folate depletion could theoretically affect ovulation or implantation, but clinical data limited. |
| Clinical Pearls | Trimethoprim/sulfamethoxazole (TMP/SMX) double strength (DS) 160/800 mg; grape flavor formulation available for pediatric use. Monitor for hyperkalemia in elderly or renal impairment due to TMP effect on potassium excretion. Contraindicated in G6PD deficiency, pregnancy (especially near term), and infants <2 months due to kernicterus risk. Use with caution in folate deficiency; supplement folinic acid in prolonged therapy. Adjust dose in creatinine clearance <30 mL/min. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Complete full course even if symptoms improve. · Avoid prolonged sun exposure; may cause photosensitivity. · Report rash, sore throat, fever, or unusual bleeding immediately. · Grape flavor: not a candy; store safely out of children's reach. · Do not take if allergic to sulfa drugs or diuretics. |