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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole in a 1:5 ratio. It works by inhibiting sequential steps in the folic acid synthesis pathway, which is essential for bacterial growth.
## Primary Indications
* Urinary Tract Infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Traveler's diarrhea (enterotoxigenic *E. coli*)
* *Stenotrophomonas maltophilia* infections
## Adult Dosing
* **General UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days.
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim component, divided into 3-4 doses, for 14-21 days.
* **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily, or 160 mg trimethoprim/800 mg sulfamethoxazole every other day.
* **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 5 days.
* **Traveler's Diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-5 days.
* **Maximum Dose:** Generally, not to exceed 640 mg trimethoprim/3200 mg sulfamethoxazole (4 DS tablets) per day.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **General Infections:** 8 mg/kg/day trimethoprim component, divided into 2 doses, every 12 hours.
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim component, divided into 3-4 doses, for 14-21 days.
* **PJP Prophylaxis:** 5 mg/kg/day trimethoprim component, divided into 2 doses, given every day or every other day.
* Maximum dose is typically 320 mg trimethoprim/1600 mg sulfamethoxazole (2 DS tablets) per day.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: Standard dose.
* CrCl 15-30 mL/min: Half the standard dose.
* CrCl < 15 mL/min: Avoid use or use with extreme caution and consider alternative agents. Dose frequency may need to be adjusted.
* **Hepatic Impairment:** Use with caution; dose adjustments are not well-defined but may be necessary.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Megaloblastic anemia due to folate deficiency.
* Marked liver or renal impairment.
* Premature infants and infants during the first 2 months of life (risk of kernicterus).
* Pregnancy at term and in breast-feeding mothers if the infant is less than 2 months old (risk of kernicterus).
## Adverse Effects
* **Common:** Nausea, vomiting, rash, urticaria, hyperkalemia.
* **Serious:** Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), Stevens-Johnson syndrome, exfoliative dermatitis, aplastic anemia, agranulocytosis, thrombocytopenia, acute liver injury, interstitial nephritis, renal failure, hyperkalemia, hyponatremia, crystalluria (especially with inadequate fluid intake).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and consider dose reduction of warfarin.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity. Consider folate supplementation.
* **Digoxin:** Increased digoxin levels. Monitor digoxin levels.
* **Cyclosporine:** Increased cyclosporine levels, potentially leading to nephrotoxicity.
* **Potassium Supplements/Potassium-Containing Salt Substitutes:** Increased risk of hyperkalemia.
* **Oral Hypoglycemics:** Potentiated hypoglycemic effect.
## Monitoring
* Complete blood counts (CBC) with differential and platelet count, especially with prolonged therapy or in immunocompromised patients.
* Renal function (BUN, creatinine).
* Electrolytes, particularly potassium.
* Liver function tests.
* Fluid intake and urine output to prevent crystalluria.
* For patients on warfarin, INR.
## Clinical Pearls
* Administer with a full glass of water and encourage adequate fluid intake to prevent crystalluria.
* Sulfonamides can displace bilirubin from albumin; avoid use in term infants and in the last trimester of pregnancy.
* Co-trimoxazole is a common cause of drug rash; advise patients to report any rash immediately.
* Consider folic acid supplementation (5-10 mg daily) in patients receiving long-term co-trimoxazole therapy to prevent hematologic effects, unless contraindicated.
* Dosing can be expressed as the amount of trimethoprim or sulfamethoxazole component, or as single strength (SS) or double strength (DS) tablets. A DS tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and local protocols for definitive guidance.
