BACTRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BACTRIM (BACTRIM).
BACTRIM (sulfamethoxazole/trimethoprim) inhibits bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, inhibits dihydropteroate synthase, blocking PABA incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking conversion of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade leads to bactericidal effect.
| Metabolism | Sulfamethoxazole is metabolized primarily via N-acetylation in the liver (N-acetyltransferase-2, NAT2). Trimethoprim is metabolized via O-demethylation and alpha-hydroxylation by cytochrome P450 (CYP) enzymes, mainly CYP3A4, with minor contribution from CYP1A2 and CYP2C9. |
| Excretion | Renal: sulfamethoxazole 20-30% unchanged, trimethoprim 40-70% unchanged; biliary/fecal: minimal (<10%) for both components. |
| Half-life | Sulfamethoxazole: 9-12 hours (prolonged in renal impairment); Trimethoprim: 8-10 hours (prolonged in renal impairment). |
| Protein binding | Sulfamethoxazole: 70% bound to albumin; Trimethoprim: 30-40% bound to albumin. |
| Volume of Distribution | Sulfamethoxazole: 0.21 L/kg; Trimethoprim: 1.8 L/kg (high tissue penetration including lung, kidney, and CSF). |
| Bioavailability | Oral: 100% for both components (well absorbed). |
| Onset of Action | Oral: 1-2 hours to therapeutic plasma concentrations; IV: immediate systemic availability. |
| Duration of Action | 12 hours (dosing interval); clinical effect persists for duration of therapy, with tissue levels maintained above MIC for susceptible pathogens. |
| Brand Substitutes | Wypal Syrup, Oysitrim Syrup, Bioprim Syrup, Twochem Syrup, Kombina 400mg/80mg Tablet, Colizole 400mg/80mg Tablet, Comax 400 mg/80 mg Tablet, Sumetrol 400mg/80mg Tablet, Otrim 400mg/80mg Tablet |
1 DS tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 10-14 days.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl >30 mL/min: No adjustment. CrCl 15-30 mL/min: 50% of standard dose. CrCl <15 mL/min: Contraindicated. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution, monitor for toxicity; consider dose reduction. Child-Pugh Class C: Avoid use. |
| Pediatric use | 8 mg/kg/day TMP / 40 mg/kg/day SMX in two divided doses every 12 hours (max 320 mg TMP/1600 mg SMX per day). For PCP treatment: 15-20 mg/kg/day TMP / 75-100 mg/kg/day SMX in 3-4 divided doses. |
| Geriatric use | Initiate at lower doses; monitor renal function closely; contraindicated if CrCl <15 mL/min; adjust based on CrCl (see renal adjustment). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BACTRIM (BACTRIM).
| Breastfeeding | Both trimethoprim and sulfamethoxazole are excreted into breast milk. M/P ratio not well defined. Potential for kernicterus in jaundiced or G6PD-deficient infants; may interfere with folate metabolism. Caution advised; consider alternative therapy. |
| Teratogenic Risk | Pregnancy Category D. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; may cause hemolytic anemia in G6PD-deficient fetuses. Avoid use, especially near term. |
■ FDA Black Box Warning
BACTRIM may cause life-threatening severe adverse reactions including: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Discontinue at first sign of skin rash or any sign of adverse reaction. Hypersensitivity reactions can occur even with re-challenge of the same or other sulfonamides.
| Serious Effects |
["Hypersensitivity to sulfonamides, trimethoprim, or any component","History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim","Megaloblastic anemia due to folate deficiency","Severe hepatic or renal impairment (CrCl <15 mL/min)","Pregnancy at term and during breastfeeding","Infants less than 2 months of age","Combination with dofetilide (increased risk of torsades de pointes)"]
| Precautions | ["Fatal hypersensitivity reactions including SJS/TEN","Hepatotoxicity and hepatic failure","Blood dyscrasias (leukopenia, thrombocytopenia, agranulocytosis)","Clostridioides difficile-associated diarrhea","Renal impairment: risk of crystalluria; maintain adequate fluid intake","Hyperkalemia in patients with renal disease or on potassium-sparing drugs","Megaloblastic anemia in folate-deficient patients","Elderly patients at increased risk of severe adverse reactions","Pregnancy: avoid near term due to risk of kernicterus (sulfonamide displaces bilirubin)","Lactation: caution; sulfonamides excreted in breast milk","Photosensitivity"] |
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| Fetal Monitoring | Monitor complete blood count (CBC) for megaloblastic anemia, leukopenia, thrombocytopenia. Assess renal function and electrolytes (potassium). Monitor for hypersensitivity reactions. Fetal ultrasound for anomaly detection if exposure occurs in first trimester. Neonatal bilirubin levels if used near term. |
| Fertility Effects | Trimethoprim may impair folate metabolism; potential effect on spermatogenesis and ovulation. Sulfamethoxazole has no known direct impact on fertility. Utilize folate supplementation if used in reproductive-age women. Reversible with discontinuation. |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, potatoes) if hyperkalemia is a concern. No specific food interactions; however, maintain adequate fluid intake to prevent crystalluria. |
| Clinical Pearls | Bactrim is contraindicated in G6PD deficiency due to risk of hemolytic anemia. Monitor renal function and potassium levels, especially in elderly patients, as sulfamethoxazole can cause hyperkalemia. Use with caution in patients with folic acid deficiency or megaloblastic anemia. Avoid in pregnancy at term and in lactating women due to risk of kernicterus. For PCP treatment, high doses may require leucovorin rescue to prevent bone marrow suppression. |
| Patient Advice | Take with a full glass of water and stay well-hydrated to prevent crystalluria. · Complete the full course even if symptoms improve. · Report any signs of allergic reaction (rash, fever, sore throat) or severe skin reactions (blistering, peeling). · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · Do not take if you have a history of sulfa allergy or are pregnant/nursing without consulting doctor. |