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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole, which act synergistically to inhibit bacterial folic acid synthesis. It is available in oral and intravenous formulations.
## Primary Indications
* Urinary tract infections (UTIs), including acute uncomplicated cystitis and acute pyelonephritis.
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment.
* Shigellosis.
* Acute otitis media.
* Traveler's diarrhea.
* Bronchitis (acute exacerbations).
* Infections caused by susceptible organisms.
## Adult Dosing
* **Urinary Tract Infections:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-7 days for cystitis, or 7-14 days for pyelonephritis.
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15-20 mg/kg/day of trimethoprim component and 75-100 mg/kg/day of sulfamethoxazole component divided into 3 or 4 doses every 24 hours for 14-21 days.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 1 DS tablet daily, or 1 DS tablet three times weekly.
* **Shigellosis:** 1 DS tablet every 12 hours for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet every 12 hours for 3 days.
Dosage is typically based on the trimethoprim component.
## Pediatric Dosing
Pediatric dosing is based on the trimethoprim component, generally 5-10 mg/kg/day. The specific dose and duration depend on the indication. For example:
* **UTIs (children > 2 months):** 8 mg/kg/day of trimethoprim and 40 mg/kg/day of sulfamethoxazole, divided into two doses every 12 hours for 7 days.
* **Pneumocystis jirovecii Pneumonia (Treatment, children > 2 months):** 15-20 mg/kg/day of trimethoprim and 75-100 mg/kg/day of sulfamethoxazole, divided into 3 or 4 doses every 24 hours for 14-21 days.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis, children > 2 months):** 5 mg/kg/day of trimethoprim and 25 mg/kg/day of sulfamethoxazole, divided into two doses daily for 3 consecutive days per week or daily.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the standard dose.
* CrCl < 15 mL/min: Avoid use. If use is essential, administer 50% of the standard dose and monitor drug levels.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented anemia due to folate deficiency.
* Infants < 2 months of age (risk of kernicterus).
* Marked liver parenchymal damage.
* Severe renal insufficiency when plasma concentrations of the drug cannot be monitored.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis, especially in patients with HIV/AIDS), pruritus, urticaria.
* **Less Common:** Diarrhea, headache, leukopenia, neutropenia, thrombocytopenia, eosinophilia, hyperkalemia.
* **Rare:** Anaphylaxis, pseudomembranous colitis, liver enzyme elevations, cholestatic jaundice, crystalluria, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Increased risk of methotrexate toxicity. Co-administration with folinic acid may be necessary.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased risk of nephrotoxicity.
* **Digoxin:** Increased digoxin levels.
* **Procainamide/N-acetylprocainamide:** Increased serum levels.
* **Oral hypoglycemics:** Increased hypoglycemic effect.
## Monitoring
* Renal function (BUN, creatinine).
* Complete blood count (CBC) with differential, especially with prolonged therapy or in immunocompromised patients.
* Electrolytes, particularly potassium.
* Liver function tests if indicated.
* Therapeutic drug monitoring may be considered in severe infections or impaired renal function.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Monitor for signs of hypersensitivity, particularly rash, and discontinue immediately if severe.
* Be aware of the increased risk of severe cutaneous adverse reactions (SCARs) in certain patient populations (e.g., HIV/AIDS patients, individuals of Han Chinese, Thai, or Native American ancestry).
* Co-trimoxazole can interfere with certain laboratory tests (e.g., creatinine by alkaline picrate method, falsely elevating it).
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*Disclaimer: This information is intended for clinical use and should not replace a thorough review of the current prescribing information, including full prescribing details and contraindications, before initiating therapy.*
