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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 oral and intravenous formulations. The standard 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 (certain pathogens)
* Infectious diarrhea (certain pathogens)
* Bacterial infections susceptible to TMP/SMX
## Adult Dosing
* **Urinary Tract Infections and Acute Exacerbations of Chronic Bronchitis:**
* 1 double-strength (DS) tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 3 to 7 days (for uncomplicated UTIs).
* Higher doses or longer durations may be required for other indications.
* **Pneumocystis jirovecii pneumonia (PJP) Treatment:**
* 15 mg/kg/day TMP component, divided into 3 or 4 doses, given IV or orally for 14 to 21 days.
* Maximum daily TMP dose: 640 mg.
* **Pneumocystis jirovecii pneumonia (PJP) Prophylaxis:**
* 1 DS tablet (160 mg TMP/800 mg SMX) orally once daily.
* Alternatively, 1 DS tablet three times weekly.
* **Other Infections:** Dosing varies widely based on the specific infection and severity. Consult reliable references.
## Pediatric Dosing
* **Urinary Tract Infections and Otitis Media:**
* 8 mg/kg/day TMP component, divided into two doses, given orally.
* Maximum daily TMP dose: 320 mg.
* Duration: Typically 3-5 days for otitis media, 7-14 days for UTIs.
* **Pneumocystis jirovecii pneumonia (PJP) Treatment:**
* 15 mg/kg/day TMP component, divided into 3 or 4 doses, given IV or orally for 14 to 21 days.
* Maximum daily TMP dose: 640 mg.
* **Pneumocystis jirovecii pneumonia (PJP) Prophylaxis:**
* 5 mg/kg/day TMP component, divided into two doses, given orally three times weekly (e.g., Monday, Tuesday, Wednesday).
* Maximum daily TMP dose: 160 mg.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is necessary based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Give 75% of the usual dose.
* CrCl < 15 mL/min: Avoid use or give 50% of the usual dose every 12 hours.
* **Hepatic Impairment:** Use with caution. No specific dosing guidelines, monitor liver function.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* History of drug-induced immune thrombocytopenia with previous use of TMP/SMX.
* Megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal insufficiency in patients where urine output cannot be monitored.
* Severe hepatic insufficiency.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis, particularly in HIV-infected patients), hyperkalemia, elevated liver enzymes, increased serum creatinine.
* **Less Common:** Anemia, leukopenia, thrombocytopenia, eosinophilia, photosensitivity, crystalluria (especially with inadequate fluid intake).
* **Rare:** Hepatic necrosis, arrhythmias, hypoglycemia.
## Key Drug Interactions
* **Warfarin:** TMP/SMX can potentiate the anticoagulant effect. Monitor INR closely and consider reducing warfarin dose.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** TMP/SMX can inhibit methotrexate metabolism and increase toxicity.
* **Dofetilide:** Increased risk of dofetilide toxicity. Contraindicated.
* **Rifampin:** May increase the rate of TMP/SMX clearance, reducing its efficacy.
* **Cyclosporine:** May increase serum creatinine levels.
* **Digoxin:** May increase serum digoxin levels.
* **Potassium Supplements/Potassium-Containing Salt Substitutes:** Increased risk of hyperkalemia.
## Monitoring
* **Renal Function:** Baseline and periodic monitoring of serum creatinine and CrCl, especially in patients with impaired renal function or receiving concurrent nephrotoxic agents.
* **Electrolytes:** Monitor potassium levels, particularly in patients with renal impairment or receiving other agents that affect potassium.
* **Hematologic Parameters:** Complete blood counts (CBC) with differential and platelet count periodically, especially with prolonged therapy or in patients with G6PD deficiency.
* **Liver Function Tests:** Periodic monitoring of LFTs.
* **Clinical Response:** Assess for improvement in signs and symptoms of infection.
* **Skin:** Monitor for rash, particularly severe or blistering rashes.
## Clinical Pearls
* Ensure adequate fluid intake to prevent crystalluria.
* TMP/SMX can cause a false-positive urine protein or creatinine assay.
* For IV administration, infuse slowly over 60 minutes to reduce the risk of hypersensitivity reactions. Do not administer as a bolus injection.
* Pregnancy: Generally avoided in the first trimester due to potential teratogenicity (folate antagonism) and near term due to risk of kernicterus in the neonate. Use only if benefits outweigh risks.
* Breastfeeding: Generally considered compatible, but caution advised in premature infants or those with G6PD deficiency.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.
