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# Co-trimoxazole (Sulfamethoxazole/Trimethoprim)
## Overview
Co-trimoxazole is a combination antibiotic consisting of sulfamethoxazole (a sulfonamide) and trimethoprim (a dihydrofolate reductase inhibitor). It provides sequential blockade of bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* *Haemophilus influenzae* meningitis (in penicillin-allergic patients)
## Adult Dosing
Dosing is typically expressed as mg of SMX/TMP.
* **Urinary Tract Infections:** 160 mg TMP / 800 mg SMX (1 double-strength tablet) every 12 hours for 3-7 days (uncomplicated) or 7-14 days (complicated).
* **Pneumocystis jirovecii pneumonia (PJP) Treatment:** 15 mg/kg/day of TMP component divided into 3-4 doses, given orally or IV for 14-21 days.
* **PJP Prophylaxis:** 1 double-strength tablet daily, or 1 single-strength tablet twice daily, or 1 double-strength tablet three times a week.
* **Shigellosis:** 160 mg TMP / 800 mg SMX every 12 hours for 5 days.
* **Acute Otitis Media:** 8-10 mg/kg/day of TMP component divided into two doses, given orally for 7-10 days.
* **Acute Exacerbations of Chronic Bronchitis:** 160 mg TMP / 800 mg SMX every 12 hours for 7 days.
## Pediatric Dosing
Dosing is typically expressed as mg of SMX/TMP.
* **General Dosing (per kg of TMP component):**
* Mild to Moderate Infections: 8 mg/kg/day TMP with 40 mg/kg/day SMX, divided into 2 doses.
* Severe Infections: 15-20 mg/kg/day TMP with 75-100 mg/kg/day SMX, divided into 3-4 doses.
* **Urinary Tract Infections (age > 2 months):** 8 mg/kg/day TMP with 40 mg/kg/day SMX, divided into two doses, for 7-14 days.
* **Pneumocystis jirovecii pneumonia (PJP) Treatment (age > 2 months):** 15 mg/kg/day TMP component divided into 3-4 doses, given orally or IV for 14-21 days.
* **PJP Prophylaxis (age > 2 months):** 5 mg/kg/day TMP component divided into two doses, with 25 mg/kg/day SMX component, given orally 3 times a week, or 10 mg/kg/day TMP component with 50 mg/kg/day SMX component given orally twice daily.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or administer one-quarter the usual dose.
* **Hepatic Impairment:** Use with caution; dose adjustments may be needed based on liver function.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim.
* Marked hyperkalemia.
* Severe renal insufficiency when frequent monitoring of plasma concentrations is not feasible.
* Infants less than 2 months of age (due to risk of kernicterus).
* Documented megaloblastic anemia due to folate deficiency.
* Late pregnancy.
## Adverse Effects
Common: Rash (non-specific, maculopapular), nausea, vomiting, diarrhea.
Serious: Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), hypersensitivity reactions (including anaphylaxis), hematologic abnormalities (e.g., anemia, leukopenia, thrombocytopenia), hyperkalemia, hyponatremia, hepatic injury, renal failure, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels; may increase toxicity. Co-administration with folic acid may be considered.
* **Cyclosporine:** Increased cyclosporine levels; monitor cyclosporine levels and renal function.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Digoxin:** Increased digoxin levels, particularly in elderly patients.
* **Thiazide Diuretics:** Increased risk of thrombocytopenia, especially in elderly patients.
## Monitoring
* Complete blood counts (CBC) with differential and platelet count (especially with prolonged therapy, in elderly patients, or those with G6PD deficiency).
* Renal function (BUN, creatinine).
* Electrolytes (especially potassium).
* Liver function tests.
* Therapeutic drug monitoring of TMP/SMX levels may be considered in severe infections or in patients with renal/hepatic impairment, though its utility is debated.
* Signs and symptoms of hypersensitivity reactions or other adverse effects.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria.
* Advise patients to report any rash, sore throat, or fever immediately.
* Avoid use in infants under 2 months of age.
* Consider folic acid supplementation (5 mg daily) for patients on long-term therapy, especially those with G6PD deficiency or certain hematologic conditions, to reduce hematologic toxicity.
* Co-trimoxazole can interfere with urine glucose testing, leading to false positives or negatives depending on the method.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*
