SULFATRIM-SS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFATRIM-SS (SULFATRIM-SS).
Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking folate synthesis. Trimethoprim inhibits bacterial dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. Sequential blockade produces bactericidal synergy.
| Metabolism | Sulfamethoxazole is primarily metabolized via N-acetylation and glucuronidation; trimethoprim is metabolized by O-demethylation and oxidation. Both are excreted renally. |
| Excretion | Renal excretion of unchanged sulfamethoxazole (SMX) approximately 20%, trimethoprim (TMP) approximately 60%; biliary/fecal elimination minor (SMX <5%, TMP <10%). |
| Half-life | SMX: 9-12 hours (increased in renal impairment); TMP: 8-11 hours (increased in renal impairment); both prolonged in elderly. |
| Protein binding | SMX: 68% bound, primarily to albumin; TMP: 40-50% bound, primarily to albumin. |
| Volume of Distribution | SMX: 0.21-0.28 L/kg; TMP: 1.5-2.0 L/kg (widespread distribution, including CSF). |
| Bioavailability | Oral: 100% for both components; IV: 100%. |
| Onset of Action | Oral: therapeutic levels in 1-4 hours; IV: therapeutic effect within 30-60 minutes. |
| Duration of Action | Dosing interval every 12 hours; bacteriostatic effect persists for 24 hours after last dose. |
1 double-strength tablet (160 mg trimethoprim / 800 mg sulfamethoxazole) orally every 12 hours for 10-14 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 15-30 mL/min: 50% of usual dose every 12 hours; CrCl <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh B/C: avoid use due to risk of hepatotoxicity. |
| Pediatric use | 8 mg trimethoprim/40 mg sulfamethoxazole per kg body weight per day, divided every 12 hours; maximum 320 mg trimethoprim/1600 mg sulfamethoxazole per day. |
| Geriatric use | Use with caution; monitor renal function and potassium levels; dose adjustment per renal function; increased risk of hyperkalemia and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULFATRIM-SS (SULFATRIM-SS).
| Breastfeeding | Sulfamethoxazole/trimethoprim (TMP-SMX) is excreted into breast milk; M/P ratio for sulfamethoxazole approximately 0.5-1.0, trimethoprim ~1.3. Concentrations in milk are low but may cause hemolytic anemia in G6PD-deficient infants or interfere with folate metabolism. Avoid in nursing mothers of ill or preterm infants. Use only if essential. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: sulfamethoxazole is a folate antagonist; risk of neural tube defects and cardiovascular malformations. Second and third trimesters: increased risk of kernicterus in neonates due to sulfonamide displacement of bilirubin from albumin, especially near term. Avoid use in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Fatalities associated with sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Avoid in patients with hypersensitivity to sulfonamides.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any component; severe hepatic or renal impairment; megaloblastic anemia due to folate deficiency; porphyria; pregnancy (especially first trimester) and lactation; concurrent use with methotrexate or dofetilide.
| Precautions | Folate deficiency risk; avoid in elderly with renal impairment, patients with megaloblastic anemia, G6PD deficiency (risk of hemolytic anemia), and severe hepatic impairment. Monitor for rash, thrombocytopenia, and electrolyte disturbances (hyperkalemia). |
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| Fetal Monitoring | Monitor maternal CBC, renal function, and liver function tests. Assess for signs of hypersensitivity, hemolysis (G6PD deficiency), and folate deficiency. Fetal monitoring: ultrasound for anomalies if used in first trimester, and monitor neonatal bilirubin after delivery if used near term. |
| Fertility Effects | No established effect on fertility. Potential for reversible folate deficiency with long-term use, which could theoretically affect gametogenesis, but clinical data are lacking. |