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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Septran is a combination antibiotic of trimethoprim and sulfamethoxazole in a 1:5 ratio. It is a broad-spectrum bacteriostatic agent that inhibits folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Acute exacerbations of chronic bronchitis
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Shigellosis
* Certain types of bacterial gastroenteritis
## Adult Dosing
* **UTIs and Shigellosis:** 160 mg TMP / 800 mg SMX (one double-strength tablet) every 12 hours for 3-7 days (UTI) or 5 days (shigellosis).
* **Acute exacerbations of chronic bronchitis:** 160 mg TMP / 800 mg SMX every 12 hours for 7-14 days.
* **PCP Treatment:** 15-20 mg TMP/kg/day divided into 3-4 doses (e.g., 320 mg TMP / 1600 mg SMX every 6 hours) for 14-21 days.
* **PCP Prophylaxis:** 160 mg TMP / 800 mg SMX once daily, or 80 mg TMP / 400 mg SMX twice daily, or 160 mg TMP / 800 mg SMX three times a week.
Maximum daily dose for adults is typically 640 mg TMP / 3200 mg SMX.
## Pediatric Dosing
Dosing is based on TMP component.
* **UTIs and most other infections:** 8 mg TMP/kg/day divided into two doses, given every 12 hours.
* For children over 12 years: adult dosing can be used.
* **PCP Treatment:** 15-20 mg TMP/kg/day divided into 3-4 doses.
* **PCP Prophylaxis:** 5 mg TMP/kg/day divided into two doses, given every 12 hours.
**Note:** For pediatric dosing, consult specific guidelines for age and weight restrictions, especially for neonates due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment (Adults):**
* CrCl > 30 mL/min: Full dose.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or use with extreme caution and at reduced doses.
Dosing adjustments for pediatric patients with renal impairment should be based on specific guidelines.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when sequential clinical response cannot be monitored.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
* **Common:** Rash (maculopapular, pruritic), nausea, vomiting, diarrhea.
* **Serious:**
* Hypersensitivity reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis).
* Hematologic effects (leukopenia, neutropenia, thrombocytopenia, megaloblastic anemia, aplastic anemia).
* Hyperkalemia.
* Hepatitis, elevated liver enzymes.
* Renal impairment.
* Photosensitivity.
* Diarrhea associated with Clostridioides difficile.
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity; may inhibit methotrexate metabolism.
* **Procainamide/Amantadine:** Increased serum levels of these drugs.
* **Diuretics (especially thiazides in the elderly):** Increased risk of thrombocytopenia.
* **Sulfonylureas:** Potential for enhanced hypoglycemic effect.
## Monitoring
* Complete blood counts (CBC) with differential periodically, especially with prolonged therapy or in patients with folate deficiency risk factors.
* Renal function (BUN, creatinine).
* Liver function tests.
* Electrolytes (especially potassium).
* For patients on warfarin, monitor INR closely.
* Monitor for signs of hypersensitivity reactions and Stevens-Johnson syndrome.
## Clinical Pearls
* TMP/SMX can cause crystalluria; ensure adequate fluid intake.
* G6PD deficiency: Use with caution; may precipitate hemolytic anemia.
* Elderly patients are at increased risk for adverse effects, particularly hematologic and dermatologic reactions.
* Alcohol may increase the risk of adverse reactions.
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*Disclaimer: This information is intended for clinical decision support and does not replace professional medical judgment. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*
