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## Sulfamethoxazole/Trimethoprim (Co-Trimoxazole) ### Overview Co-trimoxazole is a combination antibiotic consisting of sulfamethoxazole (a sulfonamide) and trimethoprim. It inhibits sequential steps in bacterial folic acid synthesis. ### Primary Indications * Urinary tract infections (UTIs) caused by susceptible organisms. * Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment. * *Shigella* gastroenteritis. * *Haemophilus influenzae* otitis media, sinusitis, and bronchitis. * Prophylaxis against UTIs in patients with recurrent infections. ### Adult Dosing * **Urinary Tract Infections (UTIs):** * Uncomplicated: 160 mg trimethoprim/800 mg sulfamethoxazole (1 double-strength tablet) PO BID for 3-7 days. * Complicated: 160 mg trimethoprim/800 mg sulfamethoxazole (1 double-strength tablet) PO BID for 7-14 days. * **Pneumocystis jirovecii Pneumonia (PJP) Treatment:** * 15-20 mg/kg/day (trimethoprim component) divided into 3-4 doses PO or IV for 14-21 days. * **PJP Prophylaxis:** * 1 double-strength tablet PO daily. * Alternatively, 1 single-strength tablet PO daily. * Or 1 double-strength tablet PO 3 times weekly. * **Shigellosis:** * 160 mg trimethoprim/800 mg sulfamethoxazole (1 double-strength tablet) PO BID for 5 days. * **Haemophilus influenzae Infections:** * 160 mg trimethoprim/800 mg sulfamethoxazole (1 double-strength tablet) PO BID for 10 days. ### Pediatric Dosing Dosing is typically based on the trimethoprim component. * **UTIs and Shigellosis:** * 8 mg/kg/day (trimethoprim component) divided into 2 doses PO. Common recommendation is 40 mg SMX/200 mg TMP per 5 mL suspension. * **PJP Treatment:** * 15-20 mg/kg/day (trimethoprim component) divided into 3-4 doses PO or IV for 14-21 days. * **PJP Prophylaxis:** * 5 mg/kg/day (trimethoprim component) divided into 2 doses PO. * Alternatively, 150 mg/m²/day (trimethoprim component) divided into 3-4 doses PO. ### Dose Adjustments * **Renal Impairment:** Dose adjustments are necessary. * CrCl > 30 mL/min: Usual dose. * CrCl 15-30 mL/min: Half the usual dose. * CrCl < 15 mL/min: Avoid use. * **Hepatic Impairment:** Use with caution. ### Contraindications * Documented hypersensitivity to trimethoprim or sulfonamides. * History of drug-induced thrombocytopenia with sulfonamides or trimethoprim. * Megaloblastic anemia due to folate deficiency. * Infants less than 2 months of age (due to risk of kernicterus). * Severe renal insufficiency (CrCl < 15 mL/min). * Severe hepatic insufficiency. * Pregnancy at term and lactation (risk of kernicterus in neonates). ### Adverse Effects Common: Nausea, vomiting, rash, hyperkalemia, and Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) which can be fatal. Other: Photosensitivity, dizziness, headache, pruritus, diarrhea, bone marrow suppression (leukopenia, thrombocytopenia, megaloblastic anemia), crystalluria, interstitial nephritis. ### Key Drug Interactions * **Warfarin:** Increased INR. Monitor INR closely. * **Methotrexate:** Increased methotrexate toxicity. * **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia. * **ACE inhibitors and ARBs:** Increased risk of hyperkalemia. * **Dofetilide:** Increased risk of dofetilide toxicity. * **Cyclosporine:** Increased risk of nephrotoxicity. * **Certain oral hypoglycemics (sulfonylureas):** May potentiate hypoglycemic effects. ### Monitoring * Renal function (BUN, creatinine). * Electrolytes, especially potassium. * Complete blood count (CBC) with differential and platelet count, particularly with prolonged therapy or in immunocompromised patients. * Signs of hypersensitivity reactions (rash, fever). ### Clinical Pearls * Encourage adequate fluid intake to prevent crystalluria. * Administer with food to minimize GI upset. * Consider folic acid supplementation (1 mg PO daily) in patients on long-term therapy, particularly those with folate deficiency or at risk. * Sulfonamides are generally contraindicated in late pregnancy due to the risk of kernicterus in the newborn. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions. Local protocols may vary.*