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# Co-trimoxazole (Septran)
## Overview
Co-trimoxazole is a combination antibiotic of sulfamethoxazole and trimethoprim. It is bactericidal by inhibiting folic acid synthesis.
## Primary Indications
* Treatment of urinary tract infections (UTIs)
* Treatment of *Pneumocystis jirovecii* pneumonia (PJP) prophylaxis and treatment
* Treatment of shigellosis
* Treatment of traveler's diarrhea
## Adult Dosing
* **Uncomplicated UTIs:** 1 double-strength (DS) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours for 3 days.
* **PJP Treatment:** 15 mg/kg/day trimethoprim component (divided into 3-4 doses) orally or IV for 14-21 days. Alternatively, 2 DS tablets every 8 hours.
* **PJP Prophylaxis:** 1 DS tablet once daily, or 1 DS tablet three times weekly.
* **Shigellosis/Traveler's Diarrhea:** 1 DS tablet every 12 hours for 5 days.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **UTIs and most other infections:** 8 mg/kg/day trimethoprim component, given as 4 mg/kg/dose every 12 hours.
* For children ≥ 2 months: Generally 10 mg/kg/day sulfamethoxazole and 2 mg/kg/day trimethoprim, divided into 2 doses.
* **PJP Prophylaxis:** 5 mg/kg/day trimethoprim component, given as 2.5 mg/kg/dose every 12 hours.
* **PJP Treatment:** 15 mg/kg/day trimethoprim component, divided into 3-4 doses.
Dosing for infants < 2 months is generally not recommended due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 25-50%.
* **Hepatic Impairment:** Use with caution. No specific dose adjustment, but monitor liver function.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* History of drug-induced thrombocytopenia with either agent.
* Infants < 2 months old (risk of kernicterus).
* Severe renal insufficiency when renal function cannot be monitored.
* Severe hepatic insufficiency.
* Megaloblastic anemia due to folate deficiency.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (can be severe, including Stevens-Johnson syndrome and toxic epidermal necrolysis), hyperkalemia, elevated transaminases.
* **Serious:** Hematologic abnormalities (anemia, neutropenia, thrombocytopenia), hypersensitivity reactions, renal impairment, hyperkalemia, photosensitivity, diarrhea (including *C. difficile*-associated).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased methotrexate levels and potential for toxicity. Avoid co-administration or monitor methotrexate levels.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Cytochrome P450 substrates:** Potential for altered levels, though clinical significance is variable.
## Monitoring
* Renal function (BUN, creatinine)
* Electrolytes (especially potassium)
* Complete blood counts (CBC) with differential, particularly with prolonged therapy or in immunocompromised patients.
* Liver function tests (LFTs).
* Signs of hypersensitivity or severe rash.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Rash should be reported immediately; may be a sign of a severe cutaneous reaction.
* Monitor potassium closely, especially in patients with renal impairment or those taking other medications that affect potassium.
* Oral suspension is available for pediatric patients. The dose for the oral suspension is typically based on the trimethoprim component (e.g., 40 mg trimethoprim/200 mg sulfamethoxazole per 5 mL).
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*Please verify the current prescribing information for definitive guidance, as recommendations may vary based on local protocols and updated clinical evidence.*
