Sulfamethoxazole + Trimethoprim is a fixed-dose combination antibiotic, commonly known as Co-trimoxazole. It is a synergistic combination of two bacteriostatic agents that sequentially inhibit two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. Sulfamethoxazole inhibits the synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. This sequential double blockade is responsible for its bactericidal action against susceptible organisms.
Adult: Standard dose: One tablet (800mg SMX + 160mg TMP) every 12 hours. For severe infections (e.g., PCP): Dose may be increased to 15-20 mg TMP/kg/day in divided doses every 6-8 hours. For UTI: One tablet BD for 3-14 days depending on severity. For chronic bronchitis: One tablet BD for 10-14 days.
Note: Administer with a full glass of water. Can be taken with or without food, but taking with food may reduce gastrointestinal upset. Maintain adequate fluid intake to prevent crystalluria. Complete the full prescribed course even if symptoms improve.
The combination acts synergistically via sequential blockade of the folic acid synthesis pathway in susceptible bacteria. Sulfamethoxazole (a sulfonamide) is a structural analog of para-aminobenzoic acid (PABA). It competitively inhibits the bacterial enzyme dihydropteroate synthase, preventing the incorporation of PABA into dihydrofolic acid. Trimethoprim (a diaminopyrimidine) inhibits the next enzyme in the pathway, dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid. Tetrahydrofolate is an essential cofactor for the synthesis of purines, thymidine, and amino acids. This dual inhibition depletes nucleotide precursors, leading to impaired DNA, RNA, and protein synthesis, resulting in a bactericidal effect.
Pregnancy: Pregnancy Category C (US FDA) / Category C (Australian). Trimethoprim is a folate antagonist. Avoid use in the first trimester due to theoretical risk of neural tube defects. Use only if potential benefit justifies the potential risk to the fetus, especially near term (risk of kernicterus). Folinic acid supplementation may be considered.
Driving: May cause dizziness, headache, or fatigue. Patients should be cautioned about operating machinery or driving until they know how the medication affects them.
| Warfarin | Increased anticoagulant effect, risk of bleeding; trimethoprim may inhibit warfarin metabolism. | Major |
| Methotrexate | Increased methotrexate toxicity (myelosuppression, hepatotoxicity) due to synergistic folate antagonism. | Major |
| Phenytoin | Increased phenytoin levels and risk of toxicity; sulfamethoxazole inhibits metabolism. | Major |
| Sulfonylureas (e.g., Glimepiride) | Enhanced hypoglycemic effect; displacement from protein binding sites. | Moderate |
| ACE Inhibitors (e.g., Ramipril) / ARBs | Increased risk of hyperkalemia, additive with trimethoprim's potassium-sparing effect. | Moderate |
| Digoxin | Possible increase in digoxin levels; trimethoprim may reduce renal clearance. | Moderate |
| Cyclosporine | Increased risk of nephrotoxicity and reduced cyclosporine efficacy. | Moderate |
| Thiazide Diuretics | Increased risk of thrombocytopenia with purpura in elderly. | Moderate |
| Zidovudine (AZT) | Increased risk of hematologic toxicity. | Moderate |
| Rifampicin | Increased clearance of trimethoprim, potentially reducing efficacy. | Moderate |