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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination antibiotic. The typical ratio is 1:5 (TMP:SMX).
## 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
* Bacterial gastroenteritis
## Adult Dosing
* **Uncomplicated UTIs:** 1 double-strength (DS) tablet (160 mg TMP/800 mg SMX) every 12 hours for 3 days.
* **Complicated UTIs and other infections:** 1 DS tablet (160 mg TMP/800 mg SMX) every 12 hours. Duration varies by indication.
* **PJP Prophylaxis:** 1 DS tablet (160 mg TMP/800 mg SMX) daily or 1 DS tablet three times weekly.
* **PJP Treatment:** 15 mg/kg TMP (divided into 4 doses) per day, given every 6 hours for 14-21 days. This typically equates to 1.5-2 DS tablets every 6 hours.
## Pediatric Dosing
Dosing is based on the TMP component, typically 5-10 mg/kg/day divided every 12 hours for UTIs and other infections. For PJP prophylaxis, 5 mg/kg TMP per day divided into two doses daily. For PJP treatment, 15 mg/kg TMP per day divided into four doses every 6 hours. Consult specific guidelines for precise pediatric dosing and duration for various indications.
## Dose Adjustments
* **Renal Impairment:**
* CrCl >30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl <15 mL/min: Avoid use.
## Contraindications
* Hypersensitivity to TMP or SMX
* Documented megaloblastic anemia due to folate deficiency
* Infants < 2 months old (risk of kernicterus)
* Severe renal or hepatic insufficiency where no reliable monitoring is possible.
## Adverse Effects
* Hematologic: Anemia, neutropenia, thrombocytopenia (especially with prolonged use or folate deficiency)
* Dermatologic: Rash, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
* Gastrointestinal: Nausea, vomiting, diarrhea
* Renal: Interstitial nephritis
* Hepatic: Elevated liver enzymes, cholestatic jaundice
* Other: Hyperkalemia, photosensitivity, DRESS syndrome.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of bone marrow suppression.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels, potential nephrotoxicity.
* **Ticlopidine/clopidogrel:** Increased risk of hematologic toxicity.
* **Tricyclic antidepressants:** Reduced efficacy of TMP/SMX.
## Monitoring
* Renal function (creatinine)
* Complete blood count (CBC) with differential, especially with prolonged therapy (>14 days) or in immunocompromised patients.
* Electrolytes, particularly potassium.
* Liver function tests with prolonged therapy.
* INR if patient is on warfarin.
## Clinical Pearls
* TMP/SMX can cause crystalluria; ensure adequate hydration.
* Consider folate supplementation in patients with risk factors for folate deficiency (e.g., elderly, malnutrition, alcoholism, concurrent use of phenytoin, or prolonged therapy).
* TMP/SMX is a sulfa-containing drug; exercise caution in patients with sulfa allergies, though cross-reactivity is not absolute.
* For PJP treatment, higher doses are used and continued for 14-21 days.
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*Always verify current prescribing information with the official product monograph or reliable drug information resources.*
