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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
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea
## Adult Dosing
Dosing is typically based on the trimethoprim component, with a standard ratio of 1:5 (trimethoprim:sulfamethoxazole).
* **Uncomplicated UTIs:** 1 DS (double strength) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-7 days.
* **PJP Treatment:** 15-20 mg/kg/day of trimethoprim, divided into 3-4 doses, for 14-21 days. This is approximately 2-3 DS tablets every 6-8 hours.
* **PJP Prophylaxis:** 1 DS tablet daily, or 1 DS tablet three times weekly.
* **Other Indications:** Dosing varies, but often ranges from 1 DS tablet twice daily to 2 DS tablets twice daily. Consult specific guidelines.
## Pediatric Dosing
Dosing is based on trimethoprim per kg.
* **UTIs and Shigellosis:** 8 mg/kg/day of trimethoprim, divided into two doses. For a DS tablet, this is approximately 1 DS tablet per 30-40 kg divided into two doses.
* **PJP Treatment:** 15-20 mg/kg/day of trimethoprim, divided into 3-4 doses.
* **PJP Prophylaxis:** 5 mg/kg/day of trimethoprim, divided into two doses, given on 3 consecutive days a week, or 10 mg/kg/day given once daily for 3 consecutive days a week.
Dosing for children < 2 months is generally not recommended due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment (CrCl > 30 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 50%.
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use or use with extreme caution and consider very low doses.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced thrombocytopenia with either component.
* Megaloblastic anemia due to folate deficiency.
* Infants < 2 months old.
* Severe renal or hepatic insufficiency when frequent monitoring of plasma concentrations is not feasible.
* Premature infants and infants in the perinatal period.
## Adverse Effects
Common: Nausea, vomiting, rash, hyperkalemia.
Serious: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe cutaneous adverse reactions (SCARs), bone marrow suppression (anemia, leukopenia, thrombocytopenia), hyperkalemia, hyponatremia, hepatic dysfunction, crystalluria.
## 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.
* **Potassium:** Risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels, especially in transplant patients.
* **Digoxin:** Increased digoxin levels.
* **Diuretics:** Increased risk of thrombocytopenia in elderly patients.
* **Sulfonylureas:** Potentiated hypoglycemic effect.
* **Tricyclic Antidepressants:** May reduce the efficacy of TCAs.
## Monitoring
* **Renal function:** Particularly in patients with pre-existing renal disease or receiving concomitant nephrotoxic agents.
* **Electrolytes:** Especially potassium.
* **Complete blood counts (CBC):** Periodic monitoring is recommended, especially with prolonged use or in immunocompromised patients.
* **Therapeutic drug monitoring:** May be considered in severe infections or specific patient populations (e.g., PJP treatment) to maintain adequate drug levels.
* **Signs of hypersensitivity:** Monitor for rash and other signs of allergic reaction.
## Clinical Pearls
* Administer with food or milk to minimize gastrointestinal upset.
* Encourage adequate fluid intake to prevent crystalluria.
* Caution in elderly patients and those with G6PD deficiency.
* Rash is a common side effect; if severe, discontinue immediately.
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*Please verify current prescribing information for the most up-to-date and complete details.*
