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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Trimethoprim/Sulfamethoxazole (TMP/SMX), commonly known as Septra or Bactrim, is a combination antibiotic. The usual ratio is 1:5 (TMP:SMX), meaning for every 1 part trimethoprim, there are 5 parts sulfamethoxazole.
## Primary Indications
* Urinary tract infections (UTIs)
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea (enterotoxigenic *E. coli*)
* MRSA skin and soft tissue infections
## Adult Dosing
* **Urinary Tract Infections (UTIs) and Shigellosis:**
* 160 mg TMP / 800 mg SMX (1 double-strength tablet) orally every 12 hours for 3 days (UTIs) or 5 days (shigellosis).
* ***Pneumocystis jirovecii* Pneumonia (PCP) Treatment:**
* 160 mg TMP / 800 mg SMX orally every 6 hours for 14 to 21 days.
* Intravenous: 15 mg/kg/day divided into 3 or 4 doses (based on TMP component), infused over 60-90 minutes.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Prophylaxis:**
* 160 mg TMP / 800 mg SMX orally once daily.
* Alternatively: 160 mg TMP / 800 mg SMX orally 3 times a week.
* **Other Infections (e.g., MRSA):** Dosing varies based on indication and severity, often 160 mg TMP / 800 mg SMX orally every 12 hours.
## Pediatric Dosing
Dosing is typically based on the trimethoprim component.
* **Urinary Tract Infections (UTIs):**
* 8 mg/kg/day of TMP (divided into 2 doses) orally every 12 hours.
* Administer as 40 mg SMX/kg/day divided into 2 doses.
* Commonly: 10 mg/kg/day (TMP component) divided into 2 doses.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Treatment:**
* 15 mg/kg/day of TMP (divided into 3 or 4 doses) orally or IV every 6 to 8 hours.
* Administer as 75 mg/kg/day (SMX component) divided into 3 or 4 doses.
* ***Pneumocystis jirovecii* Pneumonia (PCP) Prophylaxis:**
* 5 mg/kg/day of TMP (divided into 2 doses) orally every 12 hours.
* Administer as 25 mg/kg/day (SMX component) divided into 2 doses.
* Maximum dose: 160 mg TMP / 800 mg SMX daily.
Dosing for children over 12 years is typically the same as adult dosing.
## Dose Adjustments
* **Renal Impairment (CrCl > 30 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce usual maintenance dose by 25-50%.
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use or give only a loading dose; then, consider an alternative agent. If use is unavoidable, give 1/4 to 1/2 of the usual maintenance dose.
* **Hepatic Impairment:** Use with caution. Dosage adjustments are not well-defined.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented hypersensitivity to sulfites.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency where repeated laboratory determinations cannot be made.
* Megaloblastic anemia due to folate deficiency.
* Marked bone marrow depression.
* History of drug-induced immune thrombocytopenia with prior use of TMP/SMX.
## Adverse Effects
* **Common:** Rash (may be severe, including Stevens-Johnson syndrome/toxic epidermal necrolysis), nausea, vomiting, diarrhea, hyperkalemia.
* **Hematologic:** Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, megaloblastic anemia (especially with prolonged use or in folate-deficient states).
* **Renal:** Crystalluria (ensure adequate fluid intake), interstitial nephritis.
* **Hepatic:** Elevated liver enzymes, hepatitis.
* **Other:** Photosensitivity, dizziness, headache, peripheral neuropathy.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose as needed.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics / Potassium Supplements:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity. Consider increased folate supplementation or alternative agent.
* **Cyclosporine:** Increased cyclosporine levels. Monitor cyclosporine levels and renal function.
* **Digoxin:** Increased digoxin levels, especially in elderly patients or those with renal impairment.
* **Potassium-Sensing Agents (e.g., potassium supplements, ACE inhibitors):** Increased risk of hyperkalemia.
* **Potent CYP2C8 Inhibitors (e.g., paclitaxel):** May increase plasma concentrations of TMP.
* **Potent CYP2C9 Inducers (e.g., rifampin):** May decrease plasma concentrations of SMX.
* **Diuretics (especially thiazides):** Increased risk of thrombocytopenia in elderly patients.
## Monitoring
* **Renal Function:** Essential, especially in patients with pre-existing renal disease or those receiving concomitant nephrotoxic agents.
* **Complete Blood Count (CBC) with differential:** Baseline and periodically during therapy, particularly for prolonged treatment courses (>2 weeks) or in patients at risk for hematologic toxicity.
* **Liver Function Tests (LFTs):** Baseline and periodically, especially in patients with known liver disease.
* **Potassium Levels:** Especially in patients with renal impairment or those taking other medications that affect potassium.
* **Fluid Intake and Urine Output:** To prevent crystalluria.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Discontinue immediately if a rash develops. Stevens-Johnson syndrome and toxic epidermal necrolysis are rare but life-threatening.
* TMP/SMX can interfere with urine glucose and Urobilinogen tests.
* Sulfonamides are structurally related to other drugs that can cause hypersensitivity reactions (e.g., thiazides, sulfonylureas).
* Consider folic acid supplementation (e.g., 1 mg daily) for patients receiving long-term therapy, especially those at risk for folate deficiency.
* For IV administration, dilute in dextrose 5% in water and infuse over 60-90 minutes. Avoid rapid infusion.
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**Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive guidance.
