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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Trimethoprim/Sulfamethoxazole (TMP/SMX) is a combination antibiotic that inhibits bacterial folic acid synthesis. It is available in various formulations, including oral tablets (e.g., 80 mg TMP / 400 mg SMX) and intravenous solutions.
## Primary Indications
* Urinary tract infections (UTIs), acute uncomplicated cystitis
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute otitis media (less preferred due to resistance)
* Traveler's diarrhea (e.g., ETEC)
* Certain skin and soft tissue infections (e.g., MRSA, though resistance is increasing)
## Adult Dosing
* **Urinary Tract Infections (Acute Uncomplicated Cystitis):**
* Oral: 1 double-strength (DS) tablet (160 mg TMP / 800 mg SMX) every 12 hours for 3 days.
* Alternatively, 2 single-strength (80 mg TMP / 400 mg SMX) tablets every 12 hours for 3 days.
* **Pneumocystis jirovecii Pneumonia (PJP) Treatment:**
* Oral or IV: 15 mg TMP/kg/day divided into 3 or 4 doses (e.g., 20 mg TMP/kg/day divided into 4 doses for severe cases).
* Typical dose: 2 double-strength tablets every 8 hours for 14-21 days.
* Maximum TMP dose: 960 mg per day.
* **PJP Prophylaxis:**
* Oral: 1 single-strength tablet (80 mg TMP / 400 mg SMX) daily.
* Alternatively, 1 double-strength tablet three times weekly.
* Maximum TMP dose: 960 mg per day.
* **Shigellosis:**
* Oral: 1 double-strength tablet (160 mg TMP / 800 mg SMX) every 12 hours for 5 days.
* **Traveler's Diarrhea:**
* Oral: 1 double-strength tablet (160 mg TMP / 800 mg SMX) every 12 hours. Duration varies, often 3-5 days.
## Pediatric Dosing
Pediatric dosing is based on TMP component and is highly dependent on indication. **Always consult specific guidelines or protocols.**
* **PJP Prophylaxis:**
* Oral: 5 mg TMP/kg/day divided into 2 doses, given once daily or every 12 hours, administered 3 times a week on consecutive days.
* Maximum TMP dose: 960 mg/day.
* **PJP Treatment:**
* Oral or IV: 15 mg TMP/kg/day divided into 3 or 4 doses (e.g., 20 mg TMP/kg/day divided into 4 doses for severe cases).
* Maximum TMP dose: 960 mg/day.
* **UTIs and other bacterial infections:** Dosing varies widely by indication and severity. A common regimen for UTIs is 8-10 mg TMP/kg/day divided every 12 hours.
## Dose Adjustments
* **Renal Impairment:** Adjust dose based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the usual dose.
* CrCl < 15 mL/min: Avoid use or administer 50% of the usual dose every 12 hours.
## Contraindications
* Hypersensitivity to trimethoprim or sulfonamides.
* Documented severe hypersensitivity to sulfonamide-containing drugs.
* Diagnosis of megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency where pharmacokinetic monitoring is not feasible.
* Patients with porphyria.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, rash (including photosensitivity).
* **Serious:** Severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hematologic abnormalities (anemia, thrombocytopenia, leukopenia, agranulocytosis), hyperkalemia, hyponatremia, crystalluria, hepatic injury, allergic reactions (including anaphylaxis), exacerbation of gout.
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely.
* **Methotrexate:** Increased methotrexate levels; monitor for toxicity.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels, potential nephrotoxicity.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Sulfonylureas:** Potentiated hypoglycemic effect.
* **Phenytoin:** May inhibit phenytoin metabolism, increasing levels.
## Monitoring
* **Renal Function:** Especially in patients with impaired renal function or those on other nephrotoxic agents.
* **Complete Blood Count (CBC):** With differential and platelet count, particularly with prolonged therapy (>14 days) or in patients with G6PD deficiency.
* **Electrolytes:** Especially potassium and sodium.
* **Signs of hypersensitivity reactions:** Monitor for rash and other allergic symptoms.
* **Hydration and urine output:** To prevent crystalluria.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Photosensitivity is common; advise sun protection.
* Discontinue immediately if rash develops.
* TMP component can cause a reversible rise in serum creatinine (pseudo-renal failure) by inhibiting tubular secretion, without affecting glomerular filtration.
* TMP/SMX can inhibit CYP2C8 and CYP2C9, potentially affecting the metabolism of other drugs.
* For PJP prophylaxis in HIV patients, optimal timing and duration should align with current HIV treatment guidelines.
***
*Disclaimer: This information is intended for healthcare professionals. Always consult the current prescribing information and relevant guidelines before administering any medication. Local protocols may dictate specific dosing and management.*
