SULFAMETHOXAZOLE AND TRIMETHOPRIM SINGLE STRENGTH
Clinical safety rating: avoid
May increase levels of phenytoin and digoxin Can cause hyperkalemia and blood dyscrasias.
Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking folate synthesis. Trimethoprim inhibits bacterial dihydrofolate reductase, blocking tetrahydrofolate synthesis. Together, they provide sequential blockade of folate metabolism, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is metabolized primarily via N-acetylation (N-acetyltransferase 2, NAT2) and glucuronidation; trimethoprim undergoes O-demethylation (CYP3A4) and oxidation to metabolites. Both are excreted renally. |
| Excretion | Sulfamethoxazole: primarily renal (70-90% as unchanged drug and acetylated metabolite); Trimethoprim: renal (50-60% unchanged, rest as metabolites); small biliary/fecal elimination (<5% each). |
| Half-life | Sulfamethoxazole: 10-12 hours (prolonged in renal impairment); Trimethoprim: 8-11 hours (prolonged in hepatic impairment). |
| Protein binding | Sulfamethoxazole: ~70% bound to albumin; Trimethoprim: ~40-50% bound to plasma proteins. |
| Volume of Distribution | Sulfamethoxazole: 0.21-0.36 L/kg; Trimethoprim: 1.3-1.8 L/kg (total body water, indicating extensive tissue distribution). |
| Bioavailability | Oral: >90% absorbed for both components; IV: 100%. |
| Onset of Action | Oral: 1-4 hours to peak plasma concentrations; clinical effect typically within 24-48 hours. |
| Duration of Action | Approximately 12 hours; dosing interval is every 12 hours. |
1 double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) orally every 12 hours for most infections; single-strength tablet (400 mg/80 mg) is used for prophylaxis: 1 tablet orally daily.
| Dosage form | TABLET |
| Renal impairment | CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: reduce dose by 50%; CrCl <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: use with caution, consider dose reduction; Child-Pugh Class C: contraindicated due to risk of sulfonamide accumulation. |
| Pediatric use | UTI or other infections: 8 mg/kg/day trimethoprim divided every 12 hours orally; PCP prophylaxis: 150 mg/m2/day trimethoprim divided every 12 hours orally for 3 days per week. |
| Geriatric use | Use with caution due to increased risk of hyperkalemia and renal impairment; adjust dose based on renal function; avoid in elderly with CrCl <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
May increase levels of phenytoin and digoxin Can cause hyperkalemia and blood dyscrasias.
| FDA category | Positive |
| Breastfeeding | Both sulfamethoxazole and trimethoprim are excreted into breast milk. M/P ratio for sulfamethoxazole is approximately 0.1; for trimethoprim, approximately 1.2. Use caution in infants <2 months old or with G6PD deficiency, hyperbilirubinemia, or illness. Generally considered compatible with breastfeeding, but monitor for rash, jaundice, or diarrhea. |
| Teratogenic Risk |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis have occurred. Discontinue at first sign of skin rash or any sign of adverse reaction.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to sulfonamides, trimethoprim, or any component","History of drug-induced immune thrombocytopenia with sulfonamides","Megaloblastic anemia due to folate deficiency","Severe renal impairment (CrCl <15 mL/min) except for PCP prophylaxis","Pregnancy at term and nursing mothers (risk of kernicterus)","Infants <2 months of age (risk of kernicterus)","Concomitant use with dofetilide (increased risk of ventricular arrhythmias due to trimethoprim-induced QT prolongation)"]
| Precautions | ["Hypersensitivity: Discontinue at first sign of skin rash; risk of severe cutaneous reactions (SJS, TEN).","Hematologic: May cause agranulocytosis, aplastic anemia, megaloblastic anemia; monitor CBC in patients on long-term therapy.","Hepatic: Fatal hepatic necrosis reported; caution in hepatic impairment.","Renal: Dose adjustment required for creatinine clearance 15-30 mL/min; contraindicated if <15 mL/min (except for PCP prophylaxis).","Pregnancy: Avoid at term; risk of kernicterus in neonates (sulfonamide competes for bilirubin binding).","Glucose-6-phosphate dehydrogenase deficiency: Risk of hemolytic anemia.","Hyperkalemia: Trimethoprim can cause hyperkalemia, especially with renal impairment, drugs causing hyperkalemia, or in elderly.","Folate deficiency: Risk of megaloblastic anemia; consider folinic acid supplementation in prolonged therapy."] |
Loading safety data…
| First trimester: Folate antagonism may increase risk of neural tube defects, cleft palate, and cardiovascular anomalies. Second and third trimesters: Risk of kernicterus in neonates due to bilirubin displacement from albumin; hemolytic anemia in G6PD-deficient fetuses. Avoid near term due to competition with bilirubin for albumin binding. |
| Fetal Monitoring | Monitor maternal CBC, renal function, and liver function. Assess for signs of folate deficiency. In fetus: ultrasound for congenital anomalies if exposure in first trimester. Monitor neonate for jaundice, hemolysis, and kernicterus if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported. Folate antagonism may theoretically impair spermatogenesis or oogenesis but clinical evidence is lacking. |