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# Co-Trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic containing trimethoprim and sulfamethoxazole in a 1:5 ratio. It inhibits sequential steps in the folic acid synthesis pathway, leading to bacterial death.
## Primary Indications
* Urinary Tract Infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* Shigellosis
* *Haemophilus influenzae* otitis media
## Adult Dosing
* **UTIs, acute exacerbations of chronic bronchitis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days (UTIs) or 7-14 days (bronchitis).
* **PCP Treatment:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) once daily, or 3 times a week on consecutive days.
* **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 5 days.
* **Maximum Dose:** Generally not to exceed 640 mg trimethoprim (4 DS tablets) daily, except for severe infections like PCP treatment.
## Pediatric Dosing
Dosing is typically based on trimethoprim component, usually 8-10 mg/kg/day divided into two doses.
* **UTIs, otitis media:** 8 mg/kg/day of trimethoprim, given in two divided doses (e.g., 40 mg/kg/day sulfamethoxazole). For DS tablets: 1 DS tablet per 40-50 lbs (approx. 20-23 kg) per day divided into 2 doses.
* **PCP Prophylaxis:** 5 mg/kg/day of trimethoprim, given in two divided doses, on 3 days a week.
* **PCP Treatment:** 15-20 mg/kg/day of trimethoprim, given in four divided doses.
* **Maximum Dose:** Not to exceed 320 mg trimethoprim (2 DS tablets) daily for prophylaxis or routine use.
## Dose Adjustments
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 50%.
* **Renal Impairment (CrCl 30-50 mL/min):** Reduce dose by 25%.
* **Hepatic Impairment:** Use with caution; data is limited.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* History of drug-induced immune thrombocytopenia with prior use of trimethoprim or sulfonamides.
* Megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal insufficiency (CrCl < 15 mL/min) when plasma concentration monitoring cannot be performed.
* Significant liver damage.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (including Stevens-Johnson syndrome, toxic epidermal necrolysis), pruritus, eosinophilia, leukopenia, hyperkalemia.
* **Less Common:** Diarrhea, headache, dizziness, elevated liver enzymes, crystalluria (especially with inadequate fluid intake).
* **Serious:** Severe skin reactions, hematologic abnormalities (anemia, thrombocytopenia, neutropenia), hyperkalemia, hyponatremia, hepatic necrosis, renal failure, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Digoxin:** Increased digoxin levels.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Oral Contraceptives:** Potential reduced efficacy. Consider alternative contraception.
* **Cyclosporine:** Increased cyclosporine levels.
## Monitoring
* **Renal function:** Creatinine, BUN.
* **Electrolytes:** Especially potassium.
* **Complete Blood Count (CBC):** Monitor for hematologic changes, particularly with prolonged therapy or in patients with G6PD deficiency.
* **Liver function tests:** Especially with prolonged use or underlying liver disease.
* **Signs of hypersensitivity reactions:** Monitor skin closely.
* **Fluid intake:** Encourage adequate hydration to prevent crystalluria.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria and kidney damage.
* Monitor for signs of hypersensitivity reactions, especially skin rash, which can be severe.
* Use with caution in patients with G6PD deficiency, as hemolysis can occur.
* The DS (Double Strength) tablet contains 800 mg of sulfamethoxazole and 160 mg of trimethoprim.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*
