SUFLAVE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUFLAVE (SUFLAVE).
SUFLAVE is a combination of sulfamethoxazole, a sulfonamide antibiotic, and trimethoprim, a dihydrofolate reductase inhibitor. It inhibits bacterial folic acid synthesis by blocking two consecutive steps: sulfamethoxazole competes with PABA to inhibit dihydropteroate synthase, and trimethoprim inhibits dihydrofolate reductase, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is primarily metabolized via acetylation and glucuronidation; trimethoprim undergoes O-demethylation and N-oxidation. Both are substrates of CYP450 enzymes, with sulfamethoxazole metabolized by CYP2C9. |
| Excretion | Renal: 70% unchanged; fecal/biliary: 20%; 10% metabolized to inactive glucuronide |
| Half-life | Terminal elimination half-life: 3.5 hours (range 2.5–4.5 h) in healthy adults; prolonged in renal impairment (up to 10 h in anuria) |
| Protein binding | 93% bound to albumin (primary) and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 0.6 L/kg; indicates distribution into total body water with moderate tissue binding |
| Bioavailability | Oral: 55% (range 45–65%) due to first-pass metabolism; Intravenous: 100% |
| Onset of Action | Intravenous: 5–10 minutes; Oral: 1–2 hours (first-pass effect) |
| Duration of Action | Intravenous: 4–6 hours (clinical effect); Oral: 6–8 hours (dose-dependent) |
250 mg intravenously every 12 hours.
| Dosage form | FOR SOLUTION |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: 250 mg every 24 hours; hemodialysis: 250 mg after dialysis on dialysis days. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 250 mg every 24 hours; Child-Pugh C: 250 mg every 48 hours. |
| Pediatric use | 5 mg/kg intravenously every 12 hours, maximum 250 mg per dose. |
| Geriatric use | No specific adjustment recommended based on age alone; use renal function to guide dosing as in adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SUFLAVE (SUFLAVE).
| Breastfeeding | Excreted into human milk; M/P ratio not determined. Potential for serious adverse reactions in nursing infants, including hepatic impairment; contraindicated during breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category X. Risk of hepatotoxicity and severe fetal harm; contraindicated in pregnant women. First trimester: high risk of spontaneous abortion and major malformations. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and neonatal hepatotoxicity. |
| Fetal Monitoring |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and agranulocytosis have occurred. Contraindicated in patients with a history of sulfonamide or trimethoprim hypersensitivity. Avoid use in pregnancy at term and nursing mothers due to risk of kernicterus.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any component; megaloblastic anemia due to folate deficiency; severe hepatic damage; porphyria; pregnancy at term; nursing mothers; infants less than 2 months of age.
| Precautions | Risk of severe hypersensitivity reactions, hematologic toxicity (especially in folate-deficient patients), hypoglycemia in patients with renal impairment, photosensitivity, hyperkalemia with high dose trimethoprim, and increased risk of adverse events in elderly patients. |
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| Maternal: Liver function tests (ALT, AST, bilirubin) every 2 weeks, prothrombin time, serum creatinine, and CBC. Fetal: Serial ultrasound for growth restriction and amniotic fluid index; fetal echocardiography if exposure occurred in first trimester. |
| Fertility Effects | Animal studies show impaired fertility at therapeutic doses. Human data: oligospermia and menstrual irregularities reported; may reduce spermatogenesis and oogenesis; effect reversible upon discontinuation. |