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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole) ## Overview Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis. ## Primary Indications * Urinary tract infections (UTIs) * Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment * Acute exacerbations of chronic bronchitis * Shigellosis * Traveler's diarrhea (enterotoxigenic E. coli) ## Adult Dosing * **Urinary Tract Infections:** 1 double-strength (DS) tablet (160 mg trimethoprim / 800 mg sulfamethoxazole) every 12 hours for 3-7 days (depending on indication and local guidelines). * **Pneumocystis jirovecii Pneumonia (PCP) Prophylaxis:** 1 DS tablet daily, or 1 DS tablet three times a week. * **PCP Treatment:** 15-20 mg/kg/day trimethoprim component and 75-100 mg/kg/day sulfamethoxazole component, divided into 4 doses for 14-21 days. This is often rounded to 2 DS tablets every 6 hours. * **Shigellosis/Traveler's Diarrhea:** 1 DS tablet every 12 hours for 5 days. ## Pediatric Dosing Dosing is based on the trimethoprim component. * **General Infections:** 8 mg/kg/day of the trimethoprim component, divided into 2 doses every 12 hours. For example, 1 DS tablet (160 mg trimethoprim/800 mg sulfamethoxazole) per 40 lbs (approx. 18 kg) of body weight every 12 hours. * **PCP Prophylaxis:** 5 mg/kg/day trimethoprim component and 25 mg/kg/day sulfamethoxazole component, divided into 2 doses daily, or 10 mg/kg/day trimethoprim component and 50 mg/kg/day sulfamethoxazole component, divided into 2 doses every 12 hours, given 3 times per week. * **PCP Treatment:** 15-20 mg/kg/day trimethoprim component and 75-100 mg/kg/day sulfamethoxazole component, divided into 4 doses for 14-21 days. **Note:** Pediatric dosing often involves oral suspension (40 mg TMP/200 mg SMX per 5 mL). ## Dose Adjustments * **Renal Impairment:** * CrCl > 30 mL/min: No adjustment needed. * CrCl 15-30 mL/min: Administer 75% of the usual dose. * CrCl < 15 mL/min: Avoid use or administer 50% of the usual dose every 12 hours. ## Contraindications * Documented hypersensitivity to trimethoprim or sulfonamides. * History of drug-induced immune thrombocytopenia with either agent. * Marked hyperkalemia. * Severe renal insufficiency (CrCl < 15 mL/min) when frequent monitoring of plasma concentrations is impossible. * Infants less than 2 months of age (risk of kernicterus). * Megaloblastic anemia due to folate deficiency. ## Adverse Effects Common: Nausea, vomiting, rash (including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis), pruritus, eosinophilia, leukopenia, neutropenia, thrombocytopenia. Less Common: Hyperkalemia, hyponatremia, elevated liver enzymes, cholestatic jaundice, pseudomembranous colitis, headache, dizziness, tinnitus. ## Key Drug Interactions * **Warfarin:** Co-trimoxazole can potentiate the anticoagulant effect. Monitor INR closely. * **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia. * **Methotrexate:** Increased risk of methotrexate toxicity, particularly in elderly patients. * **Sulfonylureas:** Increased risk of hypoglycemia. * **Diuretics (especially thiazides in elderly):** Increased risk of thrombocytopenia. * **Rifampin:** May decrease co-trimoxazole levels. ## Monitoring * Complete blood counts (CBC) with differential at baseline and periodically during therapy, especially for prolonged courses or in immunocompromised patients. * Renal function (BUN, creatinine). * Electrolytes (especially potassium). * Liver function tests (LFTs). * For PCP treatment, monitor for clinical improvement. ## Clinical Pearls * Administer with a full glass of water and encourage increased fluid intake to prevent crystalluria. * Photosensitivity reactions can occur; advise patients to use sun protection. * Discontinue at the first sign of rash. * Monitor potassium levels, especially in patients with renal impairment or those taking other medications that affect potassium. * For PCP prophylaxis in HIV-infected patients, consider resistance patterns and adherence. *** *Please verify current prescribing information and local protocols for definitive guidance.*