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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination antibiotic that inhibits folic acid synthesis, a crucial pathway for bacterial growth. It is available in various formulations, including oral tablets, oral suspension, and intravenous solutions. The typical ratio is 1:5 TMP to SMX.
## Primary Indications
* Urinary tract infections (UTIs)
* *Pneumocystis jirovecii* pneumonia (PJP) prophylaxis and treatment
* Acute otitis media (AOM)
* Acute exacerbations of chronic bronchitis (AECB)
* Shigellosis
* Traveler's diarrhea (caused by enterotoxigenic *E. coli*)
* Certain skin and soft tissue infections, including MRSA
## Adult Dosing
* **Urinary Tract Infections:** 1 DS (double strength) tablet orally every 12 hours for 3-7 days.
* **PJP Prophylaxis:** 1 DS tablet orally daily.
* **PJP Treatment:** 15 mg/kg (TMP component) per kg/day divided into 3-4 doses intravenously or orally. Dosing is typically based on TMP content. Maximum TMP dose is 20 mg/kg/day.
* **Shigellosis/Traveler's Diarrhea:** 1 DS tablet orally every 12 hours for 5 days.
## Pediatric Dosing
Dosing is based on the TMP component.
* **Urinary Tract Infections:** 8 mg/kg/day of TMP divided into two doses orally.
* **PJP Prophylaxis:** 5 mg/kg/day of TMP divided into two doses orally, given on Tuesdays and Fridays, or 10 mg/kg/day once weekly.
* **PJP Treatment:** 15 mg/kg/day of TMP divided into 3-4 doses intravenously or orally. Maximum TMP dose is 20 mg/kg/day.
* **Acute Otitis Media:** 8-10 mg/kg/day of TMP divided into two doses orally.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is recommended for moderate to severe renal impairment (CrCl < 30 mL/min). Specific recommendations vary; consult guidelines or product information.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* History of thrombocytopenia with prior use.
* Marked anemia, megaloblastic anemia due to folate deficiency.
* Infants younger than 2 months (risk of kernicterus).
* Severe renal or hepatic insufficiency.
* Use in patients with porphyria.
## Adverse Effects
* **Common:** Gastrointestinal upset (nausea, vomiting, diarrhea), rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis), photosensitivity, pruritus.
* **Serious:** Hematologic abnormalities (anemia, leukopenia, thrombocytopenia, aplastic anemia, agranulocytosis), hyperkalemia, renal failure, hepatic dysfunction, interstitial nephritis, crystalluria (ensure adequate hydration).
## Key Drug Interactions
* **Warfarin:** TMP/SMX can potentiate the anticoagulant effect of warfarin. Monitor INR closely.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Methotrexate:** TMP/SMX can increase methotrexate levels and toxicity.
* **Phenytoin:** May increase phenytoin levels.
* **Potassium supplements/KCl:** Increased risk of hyperkalemia.
* **Rosuvastatin:** May increase rosuvastatin levels.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Tricyclic antidepressants:** May inhibit reuptake of TMP/SMX, potentially increasing TMP/SMX toxicity.
## Monitoring
* **Renal function** (BUN, creatinine)
* **Electrolytes** (especially potassium)
* **Complete blood count (CBC)** with differential, particularly with prolonged therapy or in immunocompromised patients.
* **Liver function tests**
* **Fluid intake and output** (to prevent crystalluria)
* **INR** in patients taking warfarin.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria.
* Administer with food to minimize GI upset.
* TMP/SMX can cause a false-positive urine protein assay.
* Be aware of potential for severe hypersensitivity reactions, especially in patients with a history of sulfa allergy.
* Discontinue if rash develops.
* Monitor potassium closely, especially in patients with renal impairment or those taking other medications that can increase potassium.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant guidelines for complete and up-to-date details before prescribing or administering any medication.*
