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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic that inhibits sequential steps in bacterial folic acid synthesis. It is available as oral tablets and an intravenous formulation.
## Primary Indications
* Urinary tract infections (UTIs), acute uncomplicated
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* *Shigella* gastroenteritis
* Traveler's diarrhea (due to *E. coli*)
* Prophylaxis and treatment of *Staphylococcus aureus* infections in certain populations
## Adult Dosing
* **UTIs, acute uncomplicated:** 160 mg trimethoprim / 800 mg sulfamethoxazole (one double-strength tablet) orally every 12 hours for 3 days.
* **PCP treatment:** 15-20 mg/kg/day trimethoprim component, divided into 3 or 4 doses, with 75-100 mg/kg/day sulfamethoxazole component orally or IV, given over 14-21 days.
* **PCP prophylaxis:** 160 mg trimethoprim / 800 mg sulfamethoxazole (one double-strength tablet) orally once daily, or 160 mg trimethoprim / 800 mg sulfamethoxazole (one double-strength tablet) orally 3 times a week.
* **Other infections:** Dosing varies based on infection site and severity. Typical adult doses range from 160 mg trimethoprim / 800 mg sulfamethoxazole (one double-strength tablet) orally or IV every 12 hours. Higher doses may be used for severe infections.
## Pediatric Dosing
Dosing is based on the trimethoprim component, typically 5-10 mg/kg/day divided every 12 hours for UTIs and other infections. For PCP treatment, 15-20 mg/kg/day trimethoprim component, divided every 6-8 hours. The sulfamethoxazole component dose is 5 times the trimethoprim dose. Specific weight-based calculations are crucial, and the 5:1 ratio of sulfamethoxazole to trimethoprim must be maintained. Not recommended for infants younger than 2 months due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: Usual dose.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or give 1/4 the usual dose at 12-hour intervals.
* **Hepatic Impairment:** Use with caution; monitor liver function.
## Contraindications
* Hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age.
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* History of drug-induced immune thrombocytopenia with prior use of trimethoprim or sulfonamides.
## Adverse Effects
Common: Rash, urticaria, nausea, vomiting, diarrhea.
Serious: Severe dermatologic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hyperkalemia, hyponatremia, blood dyscrasias (anemia, thrombocytopenia, leukopenia), liver injury, crystalluria, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **ACE inhibitors / ARBs / Potassium-sparing diuretics:** Increased risk of hyperkalemia. Monitor potassium levels.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Cyclosporine:** Increased cyclosporine levels, potentially leading to nephrotoxicity.
## Monitoring
* Renal function (serum creatinine).
* Electrolytes (especially potassium).
* Complete blood counts (CBC) with differential, particularly with prolonged therapy or in immunocompromised patients.
* Liver function tests.
* Signs of hypersensitivity reactions and dermatologic toxicity.
* INR if patient is on warfarin.
## Clinical Pearls
* Adequate fluid intake is essential to prevent crystalluria.
* Photosensitivity reactions can occur; advise patients to use sun protection.
* Discontinue immediately if rash or signs of hypersensitivity develop.
* Dosing for specific indications can vary based on local guidelines and susceptibility patterns.
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*Disclaimer: This information is intended for clinical use and does not replace the official prescribing information or professional judgment. Always verify current prescribing information and guidelines before administering any medication.*
