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# Co-Trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole, a synergistic antibacterial agent. The usual ratio is 1:5 (trimethoprim:sulfamethoxazole).
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Traveler's diarrhea
* Prophylaxis and treatment of other bacterial infections susceptible to the combination.
## Adult Dosing
* **Urinary Tract Infections (UTIs):**
* 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally twice daily for 3-7 days for uncomplicated UTIs.
* For complicated UTIs or pyelonephritis, duration may extend to 14 days.
* **Pneumocystis jirovecii Pneumonia (PCP) Treatment:**
* 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally every 8 hours for 14-21 days.
* **IV Dosing:** 15-20 mg/kg/day (based on trimethoprim component) divided into 3-4 doses for 14-21 days.
* **PCP Prophylaxis:**
* **Daily:** 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally once daily.
* **3 times per week:** 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally three times a week on alternate days.
* **Traveler's Diarrhea:**
* 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally twice daily for up to 5 days.
* **Other Infections:**
* Dosing varies by indication and severity. A common regimen is 160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally or IV every 12 hours.
## Pediatric Dosing
* Dosing is based on the trimethoprim component, typically 5-10 mg/kg/day divided into 2-4 doses.
* **UTIs:** 8 mg/kg/day (trimethoprim component) divided into two doses.
* **PCP Treatment:** 15-20 mg/kg/day (trimethoprim component) divided into 3-4 doses.
* **PCP Prophylaxis:** 5 mg/kg/day (trimethoprim component) divided into two doses, given 7 days a week, OR 10 mg/kg/day (trimethoprim component) divided into two doses, given on Tuesdays and Fridays.
* **General Infections:** 8-10 mg/kg/day (trimethoprim component) divided into two doses.
* **Maximum pediatric dose:** Generally not to exceed 320 mg trimethoprim / 1600 mg sulfamethoxazole (2 DS tablets) per day unless treating PCP.
## Dose Adjustments
* **Renal Impairment:**
* **CrCl > 30 mL/min:** Full dose.
* **CrCl 15-30 mL/min:** Half the usual dose.
* **CrCl < 15 mL/min:** Contraindicated or use with extreme caution and monitor levels.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* 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 immune thrombocytopenia with prior use of sulfonamides or trimethoprim.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis, particularly in patients with HIV/AIDS), hyperkalemia, elevated liver enzymes, leukopenia, thrombocytopenia, eosinophilia.
* **Serious:** Bone marrow suppression (anemia, leukopenia, thrombocytopenia), severe cutaneous reactions, hyperkalemia, hyponatremia, hepatotoxicity, crystalluria (ensure adequate hydration), hemolytic anemia (in G6PD deficient individuals).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity (bone marrow suppression).
* **Rifampin:** May decrease serum levels of trimethoprim.
* **Dofetilide:** Contraindicated due to risk of increased dofetilide plasma concentrations and torsades de pointes.
* **Oral Contraceptives:** May reduce efficacy.
## Monitoring
* Complete blood counts (CBCs) with differential and platelet counts, especially with prolonged therapy or in immunocompromised patients.
* Renal function (BUN, creatinine).
* Electrolytes (especially potassium).
* Liver function tests.
* For patients receiving long-term therapy, monitor serum folate levels.
* Monitor INR closely if co-administered with warfarin.
## Clinical Pearls
* Administer with adequate fluids to prevent crystalluria.
* TMP/SMX is a common cause of rash, including severe, life-threatening reactions. Counsel patients on signs and symptoms of hypersensitivity.
* Higher doses and prolonged therapy increase the risk of adverse effects, particularly hematologic and dermatologic.
* In patients with HIV/AIDS, co-trimoxazole is frequently used for PCP prophylaxis and treatment; they are at increased risk for adverse reactions.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and current clinical guidelines for complete details.*
