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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). They work synergistically to inhibit bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Certain respiratory tract infections
* Certain gastrointestinal infections (e.g., traveler's diarrhea)
## Adult Dosing
Dosing is typically based on the sulfamethoxazole component. The ratio of sulfamethoxazole to trimethoprim is usually 5:1. Standard strength tablets contain 400 mg sulfamethoxazole and 80 mg trimethoprim. Double strength tablets contain 800 mg sulfamethoxazole and 160 mg trimethoprim.
* **Uncomplicated UTIs:** 1 double strength tablet (800 mg/160 mg) every 12 hours for 3 days.
* **PCP Treatment:** 15 mg/kg/day (based on trimethoprim component) divided every 6 hours for 14-21 days. This typically translates to 2 double strength tablets every 6 hours.
* **PCP Prophylaxis:** 1 double strength tablet (800 mg/160 mg) daily, or 1 single strength tablet (400 mg/80 mg) twice daily.
* **Other Infections:** Dosing varies based on severity and site of infection. A common regimen is 1-2 double strength tablets (800 mg/160 mg to 1600 mg/320 mg) every 12 hours.
Maximum daily dose for adults is generally 6 double strength tablets (4800 mg/960 mg) or equivalent.
## Pediatric Dosing
Dosing is calculated based on the trimethoprim component, typically 5-10 mg/kg/day divided into two or three doses. The sulfamethoxazole dose should be 5 times the trimethoprim dose.
* **PCP Treatment:** 15 mg/kg/day (of trimethoprim) divided every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 5 mg/kg/day (of trimethoprim) divided daily or every 12 hours.
* **Other Infections:** 8-10 mg/kg/day (of trimethoprim) divided every 12 hours.
Specific product formulations (e.g., oral suspension) should be used for accurate pediatric dosing.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or use with extreme caution and monitor drug levels.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented severe adverse reactions to sulfonamides (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).
* Infants less than 2 months of age (risk of kernicterus).
* Marked anemia, megaloblastic anemia due to folate deficiency, or history of G6PD deficiency.
* Severe renal or hepatic insufficiency when facilities for monitoring plasma levels are not available.
## Adverse Effects
Common: Nausea, vomiting, rash (including photosensitivity), diarrhea, headache.
Serious: Severe rash (Stevens-Johnson syndrome, toxic epidermal necrolysis), hematologic abnormalities (anemia, leukopenia, thrombocytopenia, agranulocytosis), hyperkalemia, renal failure, liver injury, interstitial nephritis, crystalluria (ensure adequate hydration).
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely.
* **Methotrexate:** Increased methotrexate levels and toxicity; avoid co-administration or monitor methotrexate levels and CBC.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Digoxin:** Increased digoxin levels, particularly in elderly patients.
* **Oral hypoglycemics:** Increased risk of hypoglycemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with pre-existing renal disease.
* **Complete blood count (CBC):** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients. Discontinue if significant hematologic changes occur.
* **Electrolytes:** Particularly potassium.
* **Hydration:** Encourage fluid intake to prevent crystalluria.
* **Liver function tests:** Periodically, especially with prolonged therapy.
* **Therapeutic drug monitoring:** May be considered in certain situations, particularly for PCP treatment in immunocompromised individuals.
## Clinical Pearls
* Adequate fluid intake is crucial to prevent crystalluria and kidney damage.
* Photosensitivity is common; advise patients to use sun protection.
* Rash can occur up to several weeks after discontinuation; patients should be instructed to report any rash.
* Co-trimoxazole can interfere with urine glucose and protein tests.
* Avoid in G6PD deficiency due to risk of hemolytic anemia.
* Dosing for specific indications or patient populations (e.g., cystic fibrosis, burn patients) may vary based on institutional protocols or specialized guidelines.
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**Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always consult with a qualified healthcare provider and refer to the most current prescribing information before making any decisions related to medication use.
