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# Septran (Co-trimoxazole)
## Overview
Septran is a combination antibiotic of sulfamethoxazole and trimethoprim. It is available in various formulations, including oral tablets and intravenous solutions.
## Primary Indications
* Treatment of urinary tract infections (UTIs)
* Treatment of *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Treatment of shigellosis
* Treatment of otitis media
* Treatment of traveler's diarrhea (caused by susceptible organisms)
## Adult Dosing
* **Urinary Tract Infections:** 1 DS (double strength) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) orally every 12 hours for 7-14 days.
* ***Pneumocystis jirovecii* Pneumonia (Treatment):** 15 mg/kg/day of trimethoprim component (e.g., 800 mg trimethoprim / 4000 mg sulfamethoxazole per day) divided into 3 or 4 doses orally or IV for 21 days.
* ***Pneumocystis jirovecii* Pneumonia (Prophylaxis):** 1 DS tablet orally once daily, or 1 DS tablet orally 3 times a week.
* **Shigellosis:** 1 DS tablet orally every 12 hours for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet orally every 12 hours for up to 5 days.
* **IV Dosing:** Typically 8-10 mg/kg/day of trimethoprim component (given as 40-50 mg/kg/day of the combined drug) administered IV in 2-4 divided doses. Maximum IV dose: 600 mg trimethoprim and 3000 mg sulfamethoxazole per day.
Dosing for other indications may vary based on severity and local protocols.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **Urinary Tract Infections:** 8 mg/kg/day of trimethoprim component, divided into 2 doses (e.g., 40 mg/kg/day of the combined drug), given orally every 12 hours for 7-14 days.
* ***Pneumocystis jirovecii* Pneumonia (Treatment):** 15 mg/kg/day of trimethoprim component, divided into 3 or 4 doses orally or IV for 21 days.
* ***Pneumocystis jirovecii* Pneumonia (Prophylaxis):** 5 mg/kg/day of trimethoprim component, divided into 2 doses (e.g., 25 mg/kg/day of the combined drug), given orally once daily, or 150 mg/m²/day of trimethoprim component given orally twice weekly on consecutive days.
* **Shigellosis:** 8 mg/kg/day of trimethoprim component, divided into 2 doses (e.g., 40 mg/kg/day of the combined drug), given orally every 12 hours for 5 days.
* **Otitis Media:** 8 mg/kg/day of trimethoprim component, divided into 2 doses (e.g., 40 mg/kg/day of the combined drug), given orally every 12 hours for 10 days.
**Note:** For children under 2 months, safety and efficacy have not been established.
## Dose Adjustments
* **Renal Impairment:** Adjust dose based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Half of the standard dose.
* CrCl < 15 mL/min: Contraindicated.
* **Hepatic Impairment:** Use with caution; no specific dose adjustment guidelines are universally established but closer monitoring is recommended.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Infants less than 2 months of age (due to risk of kernicterus).
* Documented megaloblastic anemia due to folate deficiency.
* Severe renal insufficiency (CrCl < 15 mL/min).
* Severe hepatic insufficiency.
* History of drug-induced immune thrombocytopenia with previous use of trimethoprim or sulfonamides.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, rash, pruritus.
* **Serious:**
* **Hypersensitivity Reactions:** Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, DRESS syndrome.
* **Hematologic:** Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, megaloblastic anemia (especially in folate-deficient individuals).
* **Hepatic:** Elevated liver enzymes, hepatitis, cholestatic jaundice.
* **Renal:** Interstitial nephritis, crystalluria.
* **Neurologic:** Dizziness, headache, aseptic meningitis.
* **Cardiovascular:** QT prolongation (rare).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate toxicity. Avoid co-administration or monitor methotrexate levels and folate.
* **Digoxin:** Increased digoxin levels. Monitor digoxin levels.
* **Potassium Supplements/Potassium-Containing Salt Substitutes:** Increased risk of hyperkalemia.
* **Thiazide Diuretics:** Increased risk of thrombocytopenia, particularly in elderly patients.
* **Cyclosporine:** Increased risk of nephrotoxicity.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with pre-existing renal disease.
* **Complete Blood Counts (CBC):** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients.
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those taking other potassium-altering medications.
* **Liver function tests:** Baseline and periodically.
* **Signs of hypersensitivity reactions:** Educate patients to report any rash, fever, or signs of allergic reaction immediately.
## Clinical Pearls
* Administer oral doses with a full glass of water.
* Encourage adequate fluid intake to prevent crystalluria.
* Advise patients to report any signs of rash, sore throat, mouth sores, unusual bleeding or bruising, or jaundice.
* Co-trimoxazole can interfere with certain laboratory tests (e.g., urine glucose, creatinine).
* Consider folate supplementation for patients on long-term therapy, especially those at risk for folate deficiency (e.g., elderly, pregnant, malnourished).
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**Disclaimer:** This information is intended for clinical use and does not replace a thorough review of current prescribing information and clinical guidelines. Always consult the most up-to-date drug monograph and institutional protocols for complete details.
