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# Co-Trimoxazole (Sulfamethoxazole/Trimethoprim)
## Overview
Co-trimoxazole is a combination antibiotic containing sulfamethoxazole and trimethoprim in a 5:1 ratio. It is bactericidal and acts by inhibiting sequential steps in the folic acid synthesis pathway.
## Primary Indications
* **Urinary Tract Infections (UTIs):** Acute uncomplicated UTIs, prophylaxis.
* **Pneumocystis jirovecii Pneumonia (PJP):** Treatment and prophylaxis.
* **Bacterial Infections:** Various infections including acute otitis media, acute exacerbations of chronic bronchitis, and Shigellosis.
## Adult Dosing
* **UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 double-strength tablet) every 12 hours for 3-7 days (uncomplicated) or 7-14 days (complicated).
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim and 75-100 mg/kg/day sulfamethoxazole divided into 4 doses for 14-21 days.
* **PJP Prophylaxis:** 1 double-strength tablet daily, or 1 single-strength tablet twice daily, or 1 double-strength tablet 3 times weekly.
* **Other Infections:** Dosing varies by indication, typically 1 double-strength tablet every 12 hours.
## Pediatric Dosing
Dosing is based on trimethoprim component, usually 8-10 mg/kg/day divided into 2 doses.
* **UTIs:** 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole, divided into 2 doses, for 7 days.
* **PJP Prophylaxis:** 5 mg/kg/day trimethoprim and 25 mg/kg/day sulfamethoxazole, divided into 2 doses, on days when taken (e.g., 3 times weekly).
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim and 75-100 mg/kg/day sulfamethoxazole, divided into 4 doses, for 14-21 days.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce dose by 25-50%.
* CrCl < 15 mL/min: Avoid use.
* **Hepatic Impairment:** Use with caution; no specific dose adjustment guidelines, but monitor liver function.
## Contraindications
* Hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced immune thrombocytopenia with either component.
* Severe renal insufficiency (CrCl < 15 mL/min) if plasma concentrations cannot be monitored.
* Severe hepatic insufficiency.
* Infants < 2 months of age (risk of kernicterus).
* Megaloblastic anemia due to folate deficiency.
## Adverse Effects
* **Common:** Nausea, vomiting, rash, hyperkalemia.
* **Serious:** Stevens-Johnson syndrome, toxic epidermal necrolysis, blood dyscrasias (anemia, leukopenia, thrombocytopenia), interstitial nephritis, photosensitivity, hyperkalemia.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Cyclosporine:** Increased cyclosporine levels.
* **Potassium Chloride:** Increased risk of hyperkalemia.
* **Rifampin:** May increase clearance of co-trimoxazole.
* **Sulfonylureas:** Enhanced hypoglycemic effect.
## Monitoring
* Renal function (serum creatinine).
* Complete blood counts (CBC) with differential, especially with prolonged therapy or in immunocompromised patients.
* Electrolytes, particularly potassium.
* Liver function tests.
* Therapeutic drug levels if renal impairment or suspected toxicity.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Caution with sulfonamide allergies; cross-reactivity can occur.
* Photosensitivity is common; advise sun protection.
* Co-trimoxazole can interfere with urine glucose testing.
* In PJP prophylaxis, the thrice-weekly regimen is generally preferred for lower toxicity.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols for complete and up-to-date guidance.*
