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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole, which work synergistically to inhibit folic acid synthesis in bacteria. It is available in oral and intravenous formulations.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Bacterial prostatitis
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Infectious diarrhea
## Adult Dosing
* **Uncomplicated UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 3 days.
* **Complicated UTIs/Prostatitis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 14 days.
* **PJP Treatment:** 15 mg/kg/day of trimethoprim component, divided into 3-4 doses orally or IV, for 14-21 days. (Max 640 mg trimethoprim component per dose).
* **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally once daily, or 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally three times weekly (alternating days).
* **Shigellosis/Infectious Diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 5 days.
## Pediatric Dosing
Dosing is typically based on the trimethoprim component.
* **UTIs (2 months and older):** 8 mg/kg/day of trimethoprim component, divided into two doses every 12 hours, orally or IV.
* **PJP Treatment (2 months and older):** 15 mg/kg/day of trimethoprim component, divided into 3-4 doses orally or IV, for 14-21 days.
* **PJP Prophylaxis (2 months and older):** 5 mg/kg/day of trimethoprim component, divided into two doses every 12 hours, orally. Alternatively, 150 mg/m$^2$/day of trimethoprim component and 750 mg/m$^2$/day of sulfamethoxazole component, divided into two doses every 12 hours, for 3 consecutive days per week.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the usual dose.
* CrCl < 15 mL/min: Administer 50% of the usual dose or avoid use.
* For IV administration, adjust dosing interval based on CrCl.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Megaloblastic anemia due to folate deficiency.
* Infants < 2 months of age (increased risk of kernicterus).
* Severe renal or hepatic insufficiency where drug levels cannot be monitored.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
* **Common:** Nausea, vomiting, rash, diarrhea, urticaria.
* **Serious:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), aplastic anemia, agranulocytosis, severe hypersensitivity reactions, hyperkalemia, photosensitivity, crystalluria.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased methotrexate levels, potentially leading to bone marrow suppression. Avoid concomitant use or monitor methotrexate levels.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Phenytoin:** Increased phenytoin levels. Monitor phenytoin levels.
* **Certain antidiabetic agents (sulfonylureas):** Potentiation of hypoglycemic effect.
## Monitoring
* **Renal function:** Particularly in patients with pre-existing renal impairment or those receiving prolonged therapy.
* **Hematologic parameters:** Complete blood count (CBC) with differential, especially in patients with G6PD deficiency, folate deficiency, or prolonged therapy (e.g., weekly for treatment of PJP, monthly for prophylaxis).
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or those taking other medications that affect potassium levels.
* **Therapeutic drug levels:** May be considered in patients with severe renal impairment or PJP treatment.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Administer oral suspension with food or milk to minimize gastrointestinal upset.
* Monitor for signs and symptoms of hypersensitivity reactions, especially skin rash. Discontinue immediately if a rash appears.
* Caution in patients with G6PD deficiency due to risk of hemolytic anemia.
* IV formulation should be infused slowly over 60-90 minutes to prevent hypersensitivity reactions.
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*This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive patient management decisions.*
