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# Co-trimoxazole (Septran)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis. It is available in various oral and intravenous formulations.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea (enterotoxigenic *E. coli*)
* Nocardiosis
* Stenotrophomonas maltophilia infections
## Adult Dosing
Dosing is typically based on the trimethoprim component.
* **Urinary Tract Infections:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days (uncomplicated) or 7-14 days (complicated).
* **Pneumocystis jirovecii pneumonia (Treatment):** 15-20 mg/kg/day (as trimethoprim) divided into 3-4 doses for 14-21 days.
* **Pneumocystis jirovecii pneumonia (Prophylaxis):** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily or 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) three times weekly.
* **Other Indications:** Doses vary based on the specific infection and severity, often ranging from 160 mg to 320 mg trimethoprim twice daily.
## Pediatric Dosing
Dosing is based on ideal body weight and the trimethoprim component.
* **Urinary Tract Infections:** 8 mg/kg/day (as trimethoprim) divided into two doses.
* **Pneumocystis jirovecii pneumonia (Treatment):** 15-20 mg/kg/day (as trimethoprim) divided into 3-4 doses for 14-21 days.
* **Pneumocystis jirovecii pneumonia (Prophylaxis):** 5 mg/kg/day (as trimethoprim) divided into two doses daily, or 10 mg/kg/day (as trimethoprim) divided into three doses twice weekly.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: Full dose.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or use with extreme caution and monitor levels closely.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced immune thrombocytopenia with previous use of trimethoprim or sulfonamides.
* Marked hyperkalemia.
* Severe renal insufficiency or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* Infants less than 2 months of age (risk of kernicterus).
* Megaloblastic anemia due to folate deficiency.
## Adverse Effects
* **Hematologic:** Agranulocytosis, aplastic anemia, thrombocytopenia, neutropenia, leukopenia, megaloblastic anemia.
* **Dermatologic:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), exfoliative dermatitis, rash, urticaria, photosensitivity.
* **Gastrointestinal:** Nausea, vomiting, diarrhea, anorexia, stomatitis, glossitis.
* **Hepatic:** Elevated transaminases, hepatitis, cholestatic jaundice.
* **Renal:** Crystalluria, interstitial nephritis.
* **Other:** Hyperkalemia, hyponatremia, dizziness, headache, depression, hallucinations.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity (bone marrow suppression).
* **Cyclosporine:** Increased cyclosporine levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Rosuvastatin:** Increased rosuvastatin levels.
* **Lamivudine/Zidovudine:** Increased risk of hematologic toxicity.
## Monitoring
* Complete blood counts (CBC) with differential and platelet count, especially in patients on prolonged therapy or with risk factors for hematologic disorders.
* Renal function (serum creatinine, BUN).
* Liver function tests (LFTs).
* Electrolytes (especially potassium).
* Therapeutic drug monitoring may be considered in specific situations (e.g., severe infections, renal impairment).
* Monitor for signs of SJS/TEN.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Co-trimoxazole is generally avoided in the first trimester of pregnancy due to potential teratogenicity (folate antagonism). Use in the third trimester is also discouraged due to the risk of kernicterus in the newborn.
* Use with caution in patients with G6PD deficiency, as it can precipitate hemolytic anemia.
* Hypersensitivity reactions can occur days to weeks after initiation.
* IV formulation requires slow infusion to prevent reactions.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete and up-to-date details before making any clinical decisions.
