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# Septran (Co-Trimoxazole)
## Overview
Septran is a combination of trimethoprim and sulfamethoxazole, a sulfonamide antibiotic. It inhibits sequential steps in the folic acid synthesis pathway, leading to bacterial cell death.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute exacerbations of chronic bronchitis
## Adult Dosing
Dosing is typically expressed as mg of trimethoprim (TMP) and mg of sulfamethoxazole (SMX). Standard strength tablets contain 80 mg TMP and 400 mg SMX. High-strength tablets contain 160 mg TMP and 800 mg SMX.
* **UTIs:** 160 mg TMP/800 mg SMX every 12 hours for 3-7 days (uncomplicated) or 7-14 days (complicated).
* **PJP Treatment:** 15 mg TMP/kg/day divided into 3-4 doses (e.g., 320 mg TMP/1600 mg SMX every 6 hours) for 14-21 days.
* **PJP Prophylaxis:** 160 mg TMP/800 mg SMX daily or 160 mg TMP/800 mg SMX three times weekly.
* **Shigellosis:** 160 mg TMP/800 mg SMX every 12 hours for 5 days.
* **Acute Exacerbations of Chronic Bronchitis:** 160 mg TMP/800 mg SMX every 12 hours for 5-7 days.
Maximum daily dose: 640 mg TMP and 3200 mg SMX.
## Pediatric Dosing
Dosing is based on TMP dose, typically 5-10 mg TMP/kg/day divided every 12 hours.
* **UTIs:** 8 mg TMP/kg/day divided every 12 hours. For children >2 months, consider 10 mg TMP/kg/day divided every 8 hours for severe infections.
* **PJP Treatment:** 15 mg TMP/kg/day divided every 6 hours for 14-21 days.
* **PJP Prophylaxis:** 5 mg TMP/kg/day divided every 12 hours or 10 mg TMP/kg/day divided every 8 hours, given daily or 3 times weekly.
Dosing for infants <2 months is not routinely recommended due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment (CrCl mL/min):**
* CrCl >30: No adjustment needed.
* CrCl 15-30: Half of usual maintenance dose.
* CrCl <15: Not recommended.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants <2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* History of drug-induced immune thrombocytopenia with prior use of trimethoprim or sulfonamides.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (can be severe, including Stevens-Johnson syndrome and toxic epidermal necrolysis), hyperkalemia.
* **Hematologic:** Leukopenia, neutropenia, thrombocytopenia, megaloblastic anemia.
* **Hepatic:** Elevated liver enzymes, cholestatic jaundice.
* **Renal:** Acute interstitial nephritis.
* **Other:** Photosensitivity, crystalluria (ensure adequate fluid intake).
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **Potassium-sparing diuretics (e.g., spironolactone):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity.
* **Oral hypoglycemics:** Potentiation of hypoglycemic effect.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with impaired renal function.
* **Complete blood count (CBC) with differential:** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients. Monitor for signs of hematologic toxicity.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or those taking other medications that affect potassium levels.
* **Liver function tests:** Periodically.
* **Signs of hypersensitivity reactions:** Monitor closely.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria.
* Advise patients to report any new rash, fever, sore throat, or easy bruising/bleeding immediately.
* Discontinue if a rash develops.
* Consider folinic acid (leucovorin) rescue for patients on high-dose therapy for PJP treatment to prevent hematologic toxicity.
* Caution in patients with G6PD deficiency due to risk of hemolytic anemia.
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**Disclaimer:** This information is intended for healthcare professionals. Always verify current prescribing information and guidelines before patient care. Dosing and indications may vary based on local protocols and specific patient factors.
