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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole) ## Overview Co-trimoxazole is a combination antibiotic containing trimethoprim and sulfamethoxazole in a fixed ratio (typically 1:5). It inhibits sequential steps in bacterial folic acid synthesis. ## Primary Indications * Urinary tract infections (UTIs), including acute uncomplicated cystitis and pyelonephritis. * Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment. * Acute otitis media. * Acute exacerbations of chronic bronchitis. * Shigellosis. * Traveler's diarrhea. ## Adult Dosing * **UTIs, acute otitis media, acute exacerbations of chronic bronchitis, traveler's diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole (one double-strength tablet) every 12 hours for 3-14 days, depending on indication. * **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 5 days. * **PJP Treatment:** 160 mg trimethoprim/800 mg sulfamethoxazole every 6 hours for 10-14 days. * **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole once daily, or 3 times per week on consecutive days. ## Pediatric Dosing Dosing is typically based on the trimethoprim component, calculated as mg/kg/day divided into two or three doses. Sulfamethoxazole is dosed proportionally. * **General Infections (e.g., UTIs, otitis media):** 8 mg trimethoprim/kg/day to 10 mg trimethoprim/kg/day, given in two divided doses. * For children >12 years, adult doses apply. * Maximum: 320 mg trimethoprim/1600 mg sulfamethoxazole (two double-strength tablets) per day. * **PJP Treatment:** 15 mg trimethoprim/kg/day to 20 mg trimethoprim/kg/day, given in four divided doses every 6 hours for 10-14 days. * **PJP Prophylaxis:** 5 mg trimethoprim/kg/day to 7.5 mg trimethoprim/kg/day, given in two divided doses once daily, or 3 times per week on consecutive days. * Maximum daily dose for prophylaxis: 320 mg trimethoprim/1600 mg sulfamethoxazole. *Note: Pediatric dosing for specific indications may vary. Consult institutional guidelines or reliable pediatric drug references.* ## Dose Adjustments * **Renal Impairment (CrCl):** * CrCl >30 mL/min: No adjustment needed. * CrCl 15-30 mL/min: Administer 75% of the usual dose. * CrCl <15 mL/min: Avoid use. If unavoidable, administer 50% of the usual dose and monitor closely. ## Contraindications * Known hypersensitivity to trimethoprim or sulfonamides. * Documented severe adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, anaphylaxis, other severe skin reactions) to sulfonamides. * Marked anemia, megaloblastic anemia due to folate deficiency, or history of drug-induced megaloblastic anemia. * Infants <2 months of age (due to risk of kernicterus). * Severe hepatic insufficiency. * Severe renal insufficiency when pharmacokinetic parameters cannot be determined. * Use in the treatment of Strep. pyogenes pharyngitis (risk of rheumatic fever recurrence). ## Adverse Effects * **Common:** Nausea, vomiting, rash (including urticaria), pruritus, hyperkalemia. * **Serious:** * **Hypersensitivity:** Severe rash (Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, anaphylaxis. * **Hematologic:** Agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia, leukopenia. * **Hepatic:** Elevated transaminases, hepatitis, cholestatic jaundice. * **Renal:** Interstitial nephritis, renal failure. * **Pulmonary:** Cough, dyspnea, pulmonary infiltrates (especially in PJP treatment). * **Electrolyte:** Hyperkalemia. * **Other:** Photosensitivity, diarrhea (including C. difficile-associated). ## Key Drug Interactions * **ACE Inhibitors/ARBs:** Increased risk of hyperkalemia. * **Diuretics (especially thiazides):** Increased risk of hyperkalemia, particularly in elderly patients. * **Potassium-sparing diuretics:** Additive hyperkalemic effects. * **Warfarin:** Potentiation of anticoagulant effect; monitor INR closely. * **Methotrexate:** Increased risk of bone marrow suppression due to displacement from plasma protein binding and inhibition of dihydrofolate reductase. * **Cyclosporine:** Increased cyclosporine levels; monitor renal function and cyclosporine levels. * **Digoxin:** Increased digoxin levels, especially in elderly patients or those with renal impairment. * **Sulfonylureas (oral hypoglycemics):** Increased risk of hypoglycemia. * **Potassium supplements:** Increased risk of hyperkalemia. * **Rifampin:** May increase serum levels of sulfamethoxazole. * **Probenecid:** May increase serum levels of sulfamethoxazole and impair renal excretion of trimethoprim. ## Monitoring * **Renal function:** Baseline and periodically, especially in patients with renal impairment. * **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those taking other drugs that affect potassium levels. * **Complete blood counts (CBCs):** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients. * **Liver function tests:** Baseline and periodically, particularly in patients with pre-existing liver disease. * **Therapeutic drug monitoring:** Generally not required for routine use but may be considered in certain situations (e.g., critically ill patients, PJP treatment). * **Signs of hypersensitivity:** Monitor closely for rash and other allergic reactions. ## Clinical Pearls * Administer with a full glass of water to minimize crystalluria. * Ensure adequate hydration to prevent crystalluria. * Advise patients to report any new rash, fever, sore throat, or other signs of allergic reaction immediately. * Sulfonamides can displace bilirubin from albumin in newborns, increasing the risk of kernicterus; therefore, co-trimoxazole is contraindicated in infants younger than 2 months. * Co-trimoxazole can inhibit CYP2C9, potentially affecting the metabolism of other drugs. * Consider folate supplementation for patients on long-term therapy, especially those at risk for folate deficiency (e.g., pregnant women, elderly, malnourished). *** **Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance. This summary does not replace a comprehensive drug information review.