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# Septran (Trimethoprim/Sulfamethoxazole)
## Overview
Septran is a combination antibiotic containing trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Certain bacterial infections including otitis media, bronchitis, and shigellosis.
## Adult Dosing
* **UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days, or 80 mg trimethoprim/400 mg sulfamethoxazole (1 S tablet) every 12 hours.
* **PJP Treatment:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 6 hours for 14-21 days.
* **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily, or 3 times a week on non-consecutive days.
## Pediatric Dosing
Dosing is based on trimethoprim component, typically 5-10 mg/kg/day in 2-4 divided doses. Sulfamethoxazole dose is generally 5 times the trimethoprim dose.
* **UTIs (complicated):** 8-10 mg/kg/day (TMP component) in 2 divided doses.
* **PJP Prophylaxis:** 5 mg/kg/day (TMP component) once daily, 7 days a week, or 10 mg/kg/day (TMP component) divided into 2 doses, 3 days a week.
* **PJP Treatment:** 15-20 mg/kg/day (TMP component) in 4 divided doses.
* **Maximum doses:** Dosing should not exceed 320 mg trimethoprim/1600 mg sulfamethoxazole (2 DS tablets) per dose for treatment.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce usual dose by 50%.
* CrCl < 15 mL/min: Avoid use; if unavoidable, use 50% of the usual dose and monitor drug concentrations.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented case of megaloblastic anemia due to folate deficiency.
* Infants < 2 months of age (due to risk of kernicterus).
* Severe renal or hepatic insufficiency where there is no recurrent monitoring of drug concentrations.
## Adverse Effects
Common: Nausea, vomiting, rash, hyperkalemia.
Serious: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), blood dyscrasias (e.g., thrombocytopenia, leukopenia, aplastic anemia), hyperkalemia, renal impairment, hepatotoxicity, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased methotrexate toxicity. Avoid concurrent use or monitor methotrexate levels and for toxicity.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Cytochrome P450 (CYP) 2C9 substrates:** Potential for increased concentrations of CYP2C9 substrates.
## Monitoring
* **Renal function:** Monitor serum creatinine and eGFR, especially in patients with pre-existing renal disease or on concomitant nephrotoxic agents.
* **Electrolytes:** Monitor potassium levels, especially in patients with renal impairment or on other drugs that affect potassium.
* **Blood counts:** Monitor CBC with differential, particularly with prolonged therapy or in immunocompromised patients.
* **Liver function tests:** Monitor LFTs periodically.
* **Therapeutic drug monitoring:** Consider trimethoprim/sulfamethoxazole levels in patients with significant renal impairment or suspected toxicity.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Rash is a common side effect; discontinue if severe rash develops.
* Photosensitivity can occur; advise patients to use sun protection.
* Folic acid supplementation (5 mg daily) may be considered in patients receiving long-term therapy to reduce the risk of hematologic side effects, especially in those with folate deficiency or at risk.
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*Please verify current prescribing information with the most recent product monograph or reliable drug information resource before making clinical decisions.*
