Please check your internet connection and try again.
# Trimethoprim/Sulfamethoxazole (Co-Trimoxazole)
## Overview
Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination antibiotic. The typical ratio is 1:5 (TMP:SMX).
## Primary Indications
* Urinary tract infections (UTIs), acute uncomplicated
* *Pneumocystis jirovecii* pneumonia (PJP) prophylaxis and treatment
* *Shigella* gastroenteritis
* Bacterial prostatitis
* *Stenotrophomonas maltophilia* infections
## Adult Dosing
* **UTI, acute uncomplicated:** 1 double-strength (DS) tablet (160 mg TMP / 800 mg SMX) PO every 12 hours for 3 days.
* **PJP prophylaxis:** 1 DS tablet PO daily or 1 DS tablet PO three times weekly.
* **PJP treatment:** 15 mg TMP/kg/day divided into 4 doses (IV or PO) for 14-21 days. Maximum daily TMP dose is 640 mg.
* **Prostatitis:** 1 DS tablet PO every 12 hours for 4-6 weeks.
* **Shigellosis:** 1 DS tablet PO every 12 hours for 5 days.
## Pediatric Dosing
* Dosing is based on the trimethoprim component.
* **UTI and *Shigella*:** 8 mg TMP/kg/day divided into 2 doses (IV or PO), not to exceed 320 mg TMP daily.
* **PJP prophylaxis:** 5 mg TMP/kg/day divided into 2 doses (PO) twice weekly, or 10 mg TMP/kg/day divided into 2 doses (PO) three times weekly.
* **PJP treatment:** 15 mg TMP/kg/day divided into 4 doses (IV or PO) for 14-21 days.
## Dose Adjustments
* **Renal Impairment:**
* 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. Consult renal dosing guidelines for specific recommendations.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months old (risk of kernicterus).
* Severe renal or hepatic insufficiency when concentration cannot be monitored.
* Diagnosis or treatment of PJP in patients with AIDS and <200 cells/microL CD4+ counts or $<14\%$ CD4+ percentage, unless monitoring is performed.
## Adverse Effects
* **Common:** Rash, nausea, vomiting, diarrhea.
* **Serious:**
* Hypersensitivity reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis).
* Hematologic abnormalities (megaloblastic anemia, leukopenia, thrombocytopenia, aplastic anemia).
* Hyperkalemia.
* Hepatitis.
* Renal effects.
* *Clostridioides difficile*-associated diarrhea.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics/Potassium Supplements:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Trimeprazine:** Increased risk of blood dyscrasias.
* **Potassium Chloride:** Increased risk of hyperkalemia.
* **Levetiracetam:** Case reports of decreased levetiracetam efficacy.
## Monitoring
* Renal function (serum creatinine).
* Electrolytes, especially potassium.
* Complete blood count (CBC) with differential, particularly with prolonged therapy or in patients with G6PD deficiency.
* Liver function tests.
* INR if on warfarin.
* Signs of hypersensitivity reactions.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Administer IV TMP/SMX slowly to reduce risk of infusion reactions.
* TMP has weak potassium-sparing diuretic effects, which can lead to hyperkalemia, especially in patients with renal impairment or those taking other medications that increase potassium.
* TMP/SMX is teratogenic; avoid use in the first trimester of pregnancy due to risk of neural tube defects. Consider folate supplementation.
***
*Disclaimer: This information is intended for clinical use and does not replace comprehensive drug information resources. Always verify current prescribing information, guidelines, and patient-specific factors before making clinical decisions.*
