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# Co-Trimoxazole (Septran)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea (Enterotoxigenic E. coli)
## Adult Dosing
* **UTIs:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) orally every 12 hours for 3-7 days.
* **PCP Prophylaxis:** 1 DS tablet orally once daily.
* **PCP Treatment:** 2 DS tablets orally every 6 hours for 14-21 days.
* **Other indications:** Dosing varies by indication and severity; refer to specific guidelines. Maximum dose is typically 8 DS tablets daily.
## Pediatric Dosing
Dosing is based on trimethoprim component. For children older than 2 months:
* **UTIs:** 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole divided into two doses, administered every 12 hours for 7 days. This equates to approximately 1 DS tablet per 20 kg body weight every 12 hours.
* **PCP Prophylaxis:** 5 mg/kg/day trimethoprim and 25 mg/kg/day sulfamethoxazole divided into two doses, administered every 12 hours.
* **PCP Treatment:** 15 mg/kg/day trimethoprim and 75 mg/kg/day sulfamethoxazole divided into four doses, administered every 6 hours for 14-21 days.
* **Note:** Local protocols may dictate specific formulations and dosing adjustments for neonates and infants under 2 months due to risk of kernicterus.
## 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: Avoid use or administer 50% of the usual dose every 12 hours.
* **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 (due to risk of kernicterus).
* Severe renal or hepatic insufficiency where drug concentration cannot be monitored.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
## Adverse Effects
Common: Nausea, vomiting, rash, diarrhea, hyperkalemia.
Serious: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe rash (DRESS), blood dyscrasias (anemia, leukopenia, thrombocytopenia), liver injury, kidney injury, hyperkalemia.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **Methotrexate:** Increased methotrexate levels. Avoid concurrent use or monitor for methotrexate toxicity.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Rosuvastatin:** Increased rosuvastatin levels.
## Monitoring
* **Renal function:** Baseline and periodically during treatment, especially in patients with renal impairment.
* **Complete blood count (CBC):** Baseline and periodically during prolonged therapy (more than 14 days) or in susceptible patients.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or on other agents that increase potassium.
* **Liver function tests:** In patients with pre-existing liver disease or during prolonged therapy.
* **Therapeutic drug levels:** May be considered in severe infections or in patients with altered pharmacokinetic profiles.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Discontinue immediately if rash develops, as it may be a sign of severe hypersensitivity.
* Co-trimoxazole can interfere with urine glucose and urine protein tests.
* Caution in patients with G6PD deficiency due to potential for hemolytic anemia.
* Absorption is not significantly affected by food, but may be improved with food to reduce GI upset.
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*This information is intended for healthcare professionals and does not replace the need to consult the official product labeling and local prescribing guidelines.*
