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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole in a fixed ratio of 1:5. It inhibits sequential steps in the folic acid synthesis pathway, leading to bacterial cell death. Available as oral tablets, oral suspension, and intravenous injection.
## Primary Indications
* Urinary tract infections (UTIs), including acute uncomplicated cystitis and prophylaxis
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Traveler's diarrhea (ETEC)
* Shigellosis
* Acute otitis media
* Acute exacerbations of chronic bronchitis
## Adult Dosing
* **Urinary Tract Infections (Acute Uncomplicated Cystitis):**
* 1 DS (double strength) tablet PO BID for 3 days.
* Alternatively: 160 mg trimethoprim/800 mg sulfamethoxazole PO BID for 3 days.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Treatment:**
* 15-20 mg/kg/day trimethoprim component (e.g., 320-400 mg trimethoprim) divided into 3-4 doses, IV or PO, for 14-21 days.
* This typically equates to 2 DS tablets PO q6h or 2 DS tablets IV q6-8h, but dose calculation based on trimethoprim component is preferred.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Prophylaxis:**
* 1 DS tablet PO daily.
* Alternatively: 1 DS tablet PO 3 times a week.
* **Traveler's Diarrhea:**
* 1 DS tablet PO BID for 5 days.
* **Shigellosis:**
* 1 DS tablet PO BID for 5 days.
* **Acute Otitis Media:**
* 8-10 mg/kg/day trimethoprim component (e.g., 40 mg/kg/day total) divided into 2 doses, PO for 10 days.
* This typically equates to 2 DS tablets PO BID for 10 days, but dose calculation based on trimethoprim component is preferred.
## Pediatric Dosing
* Dosing is based on the trimethoprim component (5 mg/kg/day to 20 mg/kg/day).
* **Urinary Tract Infections and Shigellosis:** 8 mg/kg/day trimethoprim component (e.g., 40 mg/kg/day total) divided into 2 doses, PO for 5-10 days.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Treatment:** 15-20 mg/kg/day trimethoprim component divided into 3-4 doses, IV or PO, for 14-21 days.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Prophylaxis:** 5 mg/kg/day trimethoprim component (e.g., 25 mg/kg/day total) divided into 2 doses, PO daily. Or 150 mg/m²/day trimethoprim component divided into 2 doses, PO 3 times a week.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce maintenance dose by 50%.
* CrCl < 15 mL/min: Avoid use or administer only during dialysis.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency (unless serum levels are monitored).
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
## Adverse Effects
* **Common:** Rash (can be severe, including Stevens-Johnson syndrome/toxic epidermal necrolysis), nausea, vomiting, diarrhea, hyperkalemia.
* **Serious:** Hematologic toxicity (anemia, neutropenia, thrombocytopenia, aplastic anemia), hypersensitivity reactions, liver injury, renal dysfunction, photosensitivity, *Clostridioides difficile*-associated diarrhea.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics/Potassium supplements:** Increased risk of hyperkalemia. Monitor potassium levels.
* **Methotrexate:** Increased methotrexate levels and toxicity. Concurrent use generally avoided. If necessary, monitor methotrexate levels and folate supplementation may be considered.
* **Digoxin:** Increased digoxin levels. Monitor digoxin levels.
* **Cyclosporine:** Increased cyclosporine levels, especially in transplant patients. Monitor cyclosporine levels.
* **Potassium:** Increased risk of hyperkalemia.
## Monitoring
* **Renal function:** Baseline and periodic assessment of serum creatinine and BUN.
* **Complete blood count (CBC):** Baseline and periodic monitoring, especially for prolonged therapy or in immunocompromised patients.
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those taking other medications that affect potassium.
* **Liver function tests (LFTs):** Baseline and periodic assessment.
* **Therapeutic drug monitoring:** May be considered for trimethoprim in patients with renal impairment or those not responding to treatment.
## Clinical Pearls
* Adequate fluid intake is crucial to prevent crystalluria.
* Co-trimoxazole can interfere with the Jaffe method for creatinine measurement, leading to falsely elevated creatinine levels.
* Sulfonamides can displace bilirubin from albumin, increasing the risk of kernicterus in neonates; avoid in infants < 2 months old.
* Folic acid supplementation (400-800 mcg daily) may be considered during prolonged therapy or in specific patient populations (e.g., pregnancy, elderly, malnourished) to reduce the risk of hematologic side effects, but may potentially antagonize the antimicrobial effect in PCP treatment. Consult specific guidelines for PCP treatment regarding folate.
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**Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for definitive patient management decisions.
