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# Co-Trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole in a fixed ratio of 1:5. It inhibits sequential steps in bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (uncomplicated cystitis)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Traveler's diarrhea (enterotoxigenic E. coli)
* Bacterial prostatitis
* Acute exacerbations of chronic bronchitis
## Adult Dosing
* **Uncomplicated Urinary Tract Infections:** 1 DS (double strength) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3 days.
* **Pneumocystis jirovecii Pneumonia (PJP) Treatment:** 15 mg/kg/day of trimethoprim component, divided into 3 or 4 doses, given orally or IV. Duration is typically 14-21 days.
* **PJP Prophylaxis:** 1 DS tablet daily, or 1 DS tablet 3 times weekly.
* **Shigellosis:** 1 DS tablet every 12 hours for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet every 12 hours for 5 days.
* **Bacterial Prostatitis:** 1 DS tablet every 12 hours for 14-30 days.
* **Acute Exacerbations of Chronic Bronchitis:** 1 DS tablet every 12 hours for 7-14 days.
* **Maximum dose:** Generally, 8 DS tablets per day for treatment of severe infections, though this can vary based on indication and patient factors.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **Pneumocystis jirovecii Pneumonia (PJP) Treatment:** 15 mg/kg/day of trimethoprim, divided into 3 or 4 doses, given orally or IV.
* **PJP Prophylaxis:** 5 mg/kg/day of trimethoprim, divided into 2 doses, given orally 3 times weekly. Alternatively, 7.5 mg/kg every 12 hours given orally twice weekly.
* **Urinary Tract Infections:** 8 mg/kg/day of trimethoprim, divided into 2 doses.
* **Shigellosis:** 10 mg/kg/day of trimethoprim, divided into 2 doses.
* **Note:** For pediatric dosing, it is often easier to use oral suspension (50 mg TMP/250 mg SMX per 5 mL) or individual tablets. Specific concentrations and formulations may vary by manufacturer and country.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is necessary based on creatinine clearance (CrCl).
* 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.
## Contraindications
* Documented hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Megaloblastic anemia due to folate deficiency.
* Premature infants and full-term infants during the first 2 months of life.
* Severe renal insufficiency (CrCl < 15 mL/min) if plasma concentrations cannot be monitored.
* Patients with porphyria.
## Adverse Effects
* **Common:** Rash (including Stevens-Johnson syndrome/toxic epidermal necrolysis, especially in HIV-infected patients), nausea, vomiting, diarrhea, pruritus, urticaria.
* **Hematologic:** Leukopenia, thrombocytopenia, neutropenia, megaloblastic anemia, eosinophilia.
* **Hepatic:** Elevated transaminases, cholestatic jaundice, hepatitis.
* **Renal:** Increased serum creatinine, interstitial nephritis.
* **Other:** Hyperkalemia, hyponatremia, headache, dizziness, tinnitus.
## Key Drug Interactions
* **Warfarin:** Increased anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Increased methotrexate toxicity (may displace from plasma protein binding).
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Sulfonylureas:** Potentiated hypoglycemic effect.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels.
* **Tricyclic antidepressants:** May reduce efficacy.
* **Dofetilide:** Increased risk of dofetilide-induced arrhythmias.
## Monitoring
* **Renal function:** Creatinine, BUN.
* **Electrolytes:** Potassium, sodium.
* **Complete Blood Count (CBC) with differential:** Especially with prolonged therapy or in immunocompromised patients.
* **Liver function tests (LFTs):** Especially with prolonged therapy or in patients with pre-existing liver disease.
* **Therapeutic drug monitoring:** May be considered for trimethoprim levels in certain situations (e.g., severe infections, impaired renal function, suspected toxicity).
* **INR:** If co-administered with warfarin.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Patients with G6PD deficiency are at increased risk of hemolytic anemia.
* HIV-infected patients are at higher risk for severe adverse reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis and hematologic abnormalities.
* Co-trimoxazole can interfere with urine glucose and protein tests.
* The 1:5 ratio of TMP:SMX is crucial for efficacy. Do not substitute with separate components unless specifically instructed.
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*This information is intended for healthcare professionals and does not replace comprehensive prescribing information. Always consult the most current official product monograph or formulary for complete and up-to-date guidance.*
