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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole. It is a broad-spectrum bacteriostatic agent that inhibits folic acid synthesis in bacteria.
## Primary Indications
* Urinary Tract Infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Bacterial respiratory infections (e.g., acute exacerbations of chronic bronchitis)
* Shigellosis
* Traveler's diarrhea (enterotoxigenic *E. coli*)
## Adult Dosing
Dosing is typically based on the trimethoprim component, which is usually one-half of the total dose. Standard dose is 1 double-strength (DS) tablet (800 mg sulfamethoxazole / 160 mg trimethoprim) every 12 hours.
* **Uncomplicated UTIs:** 1 DS tablet every 12 hours for 3 days.
* **PCP Treatment:** 15 mg/kg/day (trimethoprim component) divided into 3 or 4 doses, given orally or IV. This typically equates to 2 DS tablets every 6 or 8 hours. Duration is usually 14-21 days.
* **PCP Prophylaxis:** 1 DS tablet once daily, or 1 DS tablet three times weekly.
* **Other Infections:** Dosing varies by infection severity and site, often 1-2 DS tablets every 12 hours.
## Pediatric Dosing
Dosing is based on the trimethoprim component: 8 mg/kg/day, divided into two doses.
* **UTIs and Shigellosis:** 8 mg/kg/day (trimethoprim) divided into 2 doses every 12 hours for 7-10 days (UTIs) or 5 days (shigellosis).
* **PCP Treatment:** 15 mg/kg/day (trimethoprim) divided into 3 or 4 doses every 6 or 8 hours.
* **PCP Prophylaxis:** 5 mg/kg/day (trimethoprim) divided into 2 doses every 12 hours, or 150 mg/m²/day (trimethoprim) divided into 2 doses. Frequency is typically daily or three times weekly.
**Note:** Pediatric dosing depends on age and weight; specific recommendations should be followed. For infants younger than 2 months, co-trimoxazole is generally not recommended due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce dose by 25-50%.
* CrCl < 15 mL/min: Avoid use. If unavoidable, monitor drug levels closely and adjust dose based on sulfamethoxazole levels.
## Contraindications
* Documented hypersensitivity to trimethoprim or sulfonamides.
* Infants < 2 months of age (risk of kernicterus).
* Severe renal insufficiency (CrCl < 15 mL/min).
* Severe hepatic insufficiency.
* Documented megaloblastic anemia due to folate deficiency.
* History of drug-induced thrombocytopenia with co-trimoxazole.
## Adverse Effects
Common: Nausea, vomiting, rash, diarrhea.
Serious:
* **Hematologic:** Agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia.
* **Dermatologic:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), exfoliative dermatitis.
* **Hepatic:** Hepatotoxicity, elevated liver enzymes.
* **Renal:** Acute interstitial nephritis, renal failure.
* **Electrolyte:** Hyperkalemia.
* **Hypersensitivity:** Anaphylaxis, serum sickness.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Digoxin:** Increased digoxin levels (particularly in patients with renal impairment or PCP).
* **Potassium Supplements / Salt Substitutes:** Increased risk of hyperkalemia.
* **CYP2C9 Substrates:** Co-trimoxazole is an inhibitor of CYP2C9; may increase levels of drugs metabolized by this enzyme (e.g., phenytoin, glipizide, glyburide).
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with impaired renal function or those on concurrent nephrotoxic agents.
* **Complete Blood Count (CBC):** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients. Monitor for signs of hematologic toxicity (fever, sore throat, purpura, jaundice).
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those taking other medications that affect potassium levels.
* **Liver function tests:** Periodically.
* **Signs of hypersensitivity reactions:** Monitor closely during treatment.
## Clinical Pearls
* Administer with food or milk to minimize gastrointestinal upset.
* Ensure adequate fluid intake to prevent crystalluria.
* In patients with PCP, consider initiating corticosteroids concomitantly to reduce risk of pulmonary deterioration, especially if oxygen saturation is < 70% or PaO2 is < 70 mmHg.
* Sulfonamides can displace bilirubin from albumin; use with caution in jaundiced infants or those at risk for kernicterus.
* Discontinue immediately if rash develops.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for complete and up-to-date details before making any clinical decisions.
