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# Co-trimoxazole (Sulfamethoxazole/Trimethoprim)
## Overview
Co-trimoxazole is a combination antibiotic of sulfamethoxazole (a sulfonamide) and trimethoprim (a dihydrofolate reductase inhibitor). These agents work synergistically to inhibit sequential steps in the bacterial folic acid synthesis pathway.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Acute otitis media
* Traveler's diarrhea
* Shigellosis
* Bronchitis (acute exacerbations)
* Nocardiosis
## Adult Dosing
**Urinary Tract Infections and Shigellosis:**
* 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 3-7 days for UTIs, or 5 days for shigellosis.
**Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis:**
* 1 DS tablet orally once daily.
* Alternatively, 1 DS tablet orally 3 times a week.
* Maximum: Generally 2 DS tablets per day for treatment.
**Pneumocystis jirovecii Pneumonia (PJP) Treatment:**
* 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) intravenously or orally every 6 hours for 14-21 days. This is the standard dose.
* Higher doses may be used for severe PJP, but specific regimens can vary by institutional protocol.
**Other Indications:**
* Dosing varies based on the specific infection and severity. For example, acute otitis media is often treated for 7 days, while acute exacerbations of chronic bronchitis may be treated for 7-10 days.
## Pediatric Dosing
Dosing is typically based on trimethoprim component, using 5 mg/kg/day of trimethoprim and 25 mg/kg/day of sulfamethoxazole, divided into two doses.
**Urinary Tract Infections:**
* 10 mg/kg/day of sulfamethoxazole and 2 mg/kg/day of trimethoprim, given orally every 12 hours.
* Duration: 7 days.
* Maximum dose should not exceed the adult dose of 1 DS tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours.
**Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis:**
* 5 mg/kg/day of trimethoprim and 25 mg/kg/day of sulfamethoxazole, given orally once daily.
* Alternatively, 15 mg/kg/day of trimethoprim and 75 mg/kg/day of sulfamethoxazole, given orally 3 times a week.
* Maximum dose should not exceed the adult dose of 1 DS tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours.
**Pneumocystis jirovecii Pneumonia (PJP) Treatment:**
* 15 mg/kg/day of trimethoprim and 75 mg/kg/day of sulfamethoxazole, divided into 4 doses, given intravenously or orally every 6 hours for 14-21 days.
* Maximum dose should not exceed the adult dose of 2 DS tablets (1600 mg sulfamethoxazole/320 mg trimethoprim) per day.
**Note:** Pediatric dosing for other indications may vary and should be guided by specific protocols.
## Dose Adjustments
* **Renal Impairment (Adults):**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce maintenance dose by 50%.
* CrCl < 15 mL/min: Avoid use; if unavoidable, administer usual maintenance dose with monitoring.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* History of drug-induced thrombocytopenia with use of sulfonamides or trimethoprim.
## Adverse Effects
Common: Nausea, vomiting, rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis), pruritus, hyperkalemia.
Less Common: Diarrhea, headache, dizziness, leukopenia, neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes, interstitial nephritis, crystalluria.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and potential for bone marrow suppression. Folate supplementation may be necessary.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels (especially in elderly patients or those with renal dysfunction).
* **Diuretics (Thiazide and Loop):** Increased risk of thrombocytopenia, particularly in elderly patients.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Phenytoin:** May inhibit phenytoin metabolism, increasing phenytoin levels.
## Monitoring
* Complete blood count (CBC) with differential and platelet count (especially with prolonged therapy or in immunocompromised patients).
* Renal function (BUN, creatinine).
* Liver function tests.
* Electrolytes (especially potassium).
* Fluid intake and urine output (to prevent crystalluria).
* INR if patient is on warfarin.
## Clinical Pearls
* Administer with food or milk to minimize gastrointestinal upset.
* Ensure adequate fluid intake to prevent crystalluria.
* Caution in patients with G6PD deficiency due to risk of hemolytic anemia.
* Consider folic acid supplementation (5 mg daily) during prolonged therapy or in patients at risk for folate deficiency to reduce hematologic toxicity, unless treating PJP where higher doses of co-trimoxazole are used.
* IV administration: Infuse slowly over 60-90 minutes to avoid infusion-related reactions. Do not administer as a bolus injection.
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*Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information or a healthcare professional for specific guidance.*
