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# Trimethoprim/Sulfamethoxazole (TMP/SMX)
## Overview
Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination antibiotic. The typical ratio is 1:5.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Otitis media
* Bronchitis
* Prophylaxis and treatment of certain bacterial infections in immunocompromised patients.
## Adult Dosing
* **Uncomplicated UTI:** 1 DS (double strength) tablet PO BID for 3 days.
* **Complicated UTI/Prostatitis:** 1 DS tablet PO BID for 10-14 days.
* **PJP Prophylaxis:** 1 DS tablet PO daily or 1 DS tablet PO three times weekly.
* **PJP Treatment:** 15-20 mg/kg/day TMP component divided into 3-4 doses PO or IV for 14-21 days. The maximum TMP dose is 20 mg/kg/day.
* **Other Infections:** 1-2 DS tablets PO or IV q12h. The maximum TMP dose is 20 mg/kg/day.
## Pediatric Dosing
* Dosing is based on the TMP component.
* **UTI:** 8 mg/kg/day TMP component given in 2 divided doses PO.
* **PJP Prophylaxis:** 5 mg/kg/day TMP component and 25 mg/kg/day SMX component given in 2 divided doses PO every other day.
* **PJP Treatment:** 15-20 mg/kg/day TMP component divided into 3-4 doses PO or IV for 14-21 days.
* Maximum TMP dose: 20 mg/kg/day.
* The DS tablet contains 160 mg TMP and 800 mg SMX.
## Dose Adjustments
* **Renal Impairment (CrCl > 30 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 50%.
* **Renal Impairment (CrCl < 15 mL/min):** Use with caution; dose reduction is necessary, but specific recommendations vary. Avoid if possible.
## Contraindications
* Documented hypersensitivity to TMP, SMX, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when therapeutic levels cannot be monitored.
* History of drug-induced thrombocytopenia with TMP/SMX.
* Porphyria.
## Adverse Effects
* **Common:** Rash, nausea, vomiting, diarrhea, hyperkalemia.
* **Serious:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe rash (DRESS), bone marrow suppression (anemia, leukopenia, thrombocytopenia), hyperkalemia, renal failure, hepatic dysfunction, pseudomembranous colitis.
## Key Drug Interactions
* **Warfarin:** TMP/SMX can potentiate the anticoagulant effect. Monitor INR closely.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Potassium supplements/Potassium-containing salt substitutes:** Increased risk of hyperkalemia.
* **Rifampin:** May decrease TMP/SMX levels.
* **L-asparaginase:** May antagonize the effect of TMP/SMX.
## Monitoring
* Renal function (BUN, creatinine).
* Electrolytes (especially potassium).
* Complete blood count (CBC) with differential and platelet count, particularly with prolonged therapy or in immunocompromised patients.
* Signs and symptoms of hypersensitivity reactions (rash).
* Liver function tests (LFTs) if clinically indicated.
* INR if patient is on warfarin.
## Clinical Pearls
* Administer with food or milk to minimize gastrointestinal upset.
* Ensure adequate fluid intake to prevent crystalluria.
* TMP can cause hyperkalemia by inhibiting renal tubular secretion of potassium.
* For PJP treatment in HIV-infected patients, TMP/SMX is the preferred agent. Consider adjunctive corticosteroids in moderate to severe PJP.
* Caution in patients with G6PD deficiency due to risk of hemolytic anemia.
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*Please consult the current prescribing information for complete details and specific indications.*
