Co-Trimoxazole

# Co-Trimoxazole ## Overview Co-Trimoxazole is a fixed-dose combination of trimethoprim (TMP) and sulfamethoxazole (SMX) in a 1:5 ratio. It is a bacteriostatic antibiotic that inhibits sequential steps in microbial folate synthesis. ## Primary Indications - Urinary tract infections (UTIs) – acute uncomplicated - Pneumocystis jirovecii pneumonia (PCP) – treatment and prophylaxis - Shigellosis, traveler’s diarrhea - Toxoplasmosis (in combination) - Nocardiosis, Stenotrophomonas infections ## Adult Dosing - **UTI (uncomplicated):** 1 DS tablet (TMP 160 mg/SMX 800 mg) orally every 12 hours for 3–7 days - **PCP treatment:** TMP 15–20 mg/kg/day + SMX 75–100 mg/kg/day orally or IV in 3–4 divided doses for 14–21 days - **PCP prophylaxis:** 1 DS tablet orally once daily (alternative: 1 SS tablet daily) - **Toxoplasmosis:** 1 DS tablet every 6–12 hours (dose varies, follow local protocol) ## Pediatric Dosing - **UTI / general infections:** TMP 8–12 mg/kg/day + SMX 40–60 mg/kg/day orally divided every 12 hours; max = 1 DS tablet per dose - **PCP treatment:** TMP 15–20 mg/kg/day + SMX 75–100 mg/kg/day orally or IV divided every 6–8 hours (up to 21 days) - **PCP prophylaxis:** TMP 150 mg/m²/day + SMX 750 mg/m²/day orally divided twice daily, 3 days per week (e.g., Monday/Tuesday/Wednesday). Alternatively, 5 mg/kg TMP (as component) orally once daily (max 320 mg TMP/day). Exact dosing depends on age and local protocol. ## Dose Adjustments - **Renal impairment (CrCl):** - CrCl >30 mL/min: standard dose - CrCl 15–30 mL/min: 50% of usual dose - CrCl <15 mL/min: avoid use (or reduce significantly per local protocol) - **Hemodialysis:** Dose post-dialysis; avoid if CrCl <15 unless for PCP (then monitor carefully) - **Hepatic impairment:** Severe impairment – avoid if significant liver damage ## Contraindications - Hypersensitivity to sulfonamides, trimethoprim, or any component - Severe hepatic or renal insufficiency (see Dose Adjustments) - Megaloblastic anemia due to folate deficiency - Infants <2 months of age (risk of kernicterus) - Pregnancy – avoid near term (risk of neonatal jaundice, kernicterus) - Breastfeeding – caution (avoid if infant premature or jaundiced) ## Adverse Effects - Rash, urticaria, photosensitivity; Stevens-Johnson syndrome (rare, but serious) - Nausea, vomiting, diarrhea; hyperkalemia (especially with higher doses) - Bone marrow suppression (leukopenia, thrombocytopenia) – folate-dependent - Hepatotoxicity, pancreatitis, interstitial nephritis - Aseptic meningitis, hypoglycemia (especially in renal impairment) ## Key Drug Interactions - **Warfarin:** Potentiation of anticoagulant effect (INR increase) - **Methotrexate:** Increased risk of bone marrow suppression (folate antagonism) - **ACE inhibitors:** Risk of hyperkalemia - **Sulfonylureas:** Increased hypoglycemic effect - **Phenytoin:** Prolonged phenytoin half-life - **Cyclosporine:** Decrease in cyclosporine levels (possible) ## Monitoring - Baseline CBC, renal function, liver enzymes; repeat CBC weekly during prolonged therapy (especially high dose PCP) - Serum potassium during high-dose therapy - Signs of rash, jaundice, bleeding, or infection ## Clinical Pearls - DS = double strength (TMP 160 mg/SMX 800 mg); SS = single strength (80/400 mg) - For PCP treatment, IV route is preferred in moderate–severe cases (oral only if mild) - In HIV/AIDS, PCP prophylaxis is first-line; desensitization may be considered in mild–moderate sulfa allergy (not for severe reactions) - Use with caution in elderly (renal function, electrolyte disturbances) - Always crystallize with adequate oral/intravenous fluids to reduce risk of crystalluria --- **Educational Disclaimer:** This information is for educational purposes and does not replace individual clinical judgment. Dosing, indications, and safety considerations may vary by local protocols, patient factors, and evolving evidence. Always verify with current prescribing information and consult appropriate references before making clinical decisions.