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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Traveler's diarrhea (enterotoxigenic E. coli)
* Infections caused by susceptible organisms, including some respiratory and skin infections.
## Adult Dosing
Dosing is typically expressed as double strength (DS) tablets (800 mg sulfamethoxazole / 160 mg trimethoprim) or single strength (SS) tablets (400 mg sulfamethoxazole / 80 mg trimethoprim). Ratios are usually 5:1 SMX:TMP.
* **Uncomplicated UTIs:** 1 DS tablet (160/800 mg) PO BID for 3-7 days.
* **PJP Treatment:** 15-20 mg/kg/day of trimethoprim component divided into 3-4 doses PO or IV for 14-21 days. This is approximately 2 DS tablets PO QID.
* **PJP Prophylaxis:** 1 DS tablet PO daily or 1 SS tablet PO BID.
* **Shigellosis:** 1 DS tablet PO BID for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet PO BID for 3-5 days.
Maximum dose: Generally, no more than 2 DS tablets (320/1600 mg) every 12 hours for adults, unless treating severe PJP.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **UTIs (except PJP):** 8 mg/kg/day of trimethoprim component divided into 2 doses PO. This is approximately 1 SS tablet PO BID for children 6 weeks to 6 months, and 1 DS tablet PO BID for children >6 months (adjust based on weight).
* **PJP Treatment:** 15-20 mg/kg/day of trimethoprim component divided into 3-4 doses PO or IV for 14-21 days.
* **PJP Prophylaxis:** 5 mg/kg/day of trimethoprim component divided into 2 doses PO, given BID, not to exceed 1 DS tablet daily.
## Dose Adjustments
* **Renal Impairment (CrCl < 30 mL/min):** Dose reduction and/or increased dosing interval is necessary.
* CrCl 15-30 mL/min: Administer usual initial dose, then 1/2 the usual maintenance dose every 12 hours.
* CrCl < 15 mL/min: Avoid use or administer 1/2 the usual maintenance dose every 12 hours.
* **Hepatic Impairment:** Use with caution; dose adjustment may be needed.
## Contraindications
* Documented hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Infants < 2 months of age (risk of kernicterus).
* Megaloblastic anemia due to folate deficiency.
* Severe renal or hepatic insufficiency where urine or blood concentrations cannot be monitored.
* History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea, pruritus.
Serious: Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hyperkalemia, bone marrow suppression (anemia, leukopenia, thrombocytopenia), hepatitis, crystalluria (ensure adequate fluid intake), hypersensitivity reactions.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose as needed.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Thiazide Diuretics:** Increased risk of thrombocytopenia, especially in elderly patients.
* **Tricyclic Antidepressants:** May decrease efficacy.
## Monitoring
* Renal function (BUN, creatinine).
* Electrolytes (especially potassium).
* Complete blood counts (CBC) with differential, particularly with prolonged therapy or in immunocompromised patients.
* Liver function tests.
* Signs of hypersensitivity and skin reactions.
* Fluid intake and output (to prevent crystalluria).
## Clinical Pearls
* Administer with food or milk to minimize gastrointestinal upset.
* Ensure adequate fluid intake to prevent crystalluria.
* Caution in patients with G6PD deficiency (risk of hemolytic anemia).
* Avoid in pregnancy, especially in the third trimester, due to risk of kernicterus.
* Elderly patients may be at increased risk for adverse effects, particularly bone marrow suppression and hypersensitivity.
* The dose is usually expressed as mg of trimethoprim/mg of sulfamethoxazole.
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*Disclaimer: This information is intended for clinical pharmacists and healthcare professionals. Always consult the most current prescribing information and relevant guidelines for definitive patient care decisions.*
