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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole. It is available in various strengths, typically as tablets containing 80 mg trimethoprim and 400 mg sulfamethoxazole.
## Primary Indications
* Treatment of urinary tract infections (UTIs)
* Treatment of *Pneumocystis jirovecii* pneumonia (PCP)
* Treatment and prophylaxis of *Pneumocystis jirovecii* pneumonia (PCP) in immunocompromised patients
* Treatment of traveler's diarrhea
* Treatment of certain respiratory tract infections (e.g., acute exacerbations of chronic bronchitis)
* Treatment of otitis media
## Adult Dosing
Dosing varies significantly by indication. General guidelines:
* **Urinary Tract Infections (Uncomplicated):** 1 double-strength (DS) tablet (160 mg trimethoprim / 800 mg sulfamethoxazole) every 12 hours for 3-7 days.
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15 mg/kg/day (trimethoprim component) divided into 3-4 doses, not to exceed 640 mg trimethoprim or 3200 mg sulfamethoxazole per day, for 14-21 days. This is often approximated as 2 DS tablets every 6 hours.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 1 DS tablet (160 mg trimethoprim / 800 mg sulfamethoxazole) daily, or 1 DS tablet 3 times per week.
* **Traveler's Diarrhea:** 1 DS tablet every 12 hours for 3-5 days.
Consult local guidelines for specific indications and duration.
## Pediatric Dosing
Dosing is based on the trimethoprim component and weight.
* **General Infections:** 8-10 mg/kg/day (trimethoprim component) divided into two doses. For example, for a 20 kg child, this would be 160-200 mg of trimethoprim per day, typically given as 1/2 DS tablet twice daily.
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15 mg/kg/day (trimethoprim component) divided into 3-4 doses for 14-21 days.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 5-7.5 mg/kg/day (trimethoprim component) divided into 1-2 doses daily, or 150 mg/m²/day (trimethoprim component) divided into 2 doses, 3 days per week.
Maximum pediatric doses vary by indication and should be guided by specific pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the standard dose.
* CrCl < 15 mL/min: Avoid use or administer 50% of the standard dose at 12-hour intervals. Dose should be guided by therapeutic drug monitoring.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Infants less than 2 months of age (risk of kernicterus).
* Documented megaloblastic anemia due to folate deficiency.
* Severe renal or hepatic insufficiency where urine or blood levels cannot be monitored.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
* **Common:** Rash, pruritus, nausea, vomiting, diarrhea, anorexia.
* **Serious:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe cutaneous adverse reactions (SCARs), hypersensitivity reactions (including anaphylaxis), hematologic abnormalities (anemia, leukopenia, thrombocytopenia, eosinophilia, neutropenia), hyperkalemia, hyponatremia, hepatic injury, crystalluria, photosensitivity, C. difficile-associated diarrhea.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose as needed.
* **Methotrexate:** Increased methotrexate levels and potential for toxicity. Concomitant use generally avoided unless folate supplementation is provided and methotrexate levels are monitored.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics/Potassium supplements:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Digoxin:** Increased digoxin levels.
* **Potent CYP2C8 inhibitors (e.g., gemfibrozil):** May increase levels of trimethoprim.
* **Potent CYP2C9 inducers (e.g., rifampin):** May decrease levels of sulfamethoxazole.
* **Thiazide diuretics:** Increased risk of thrombocytopenia in elderly patients.
## Monitoring
* **Renal function:** Baseline and during therapy, especially in patients with pre-existing renal disease or those receiving concomitant nephrotoxic agents.
* **Complete blood counts (CBC):** Baseline and periodically during therapy, particularly for prolonged treatment courses or in immunocompromised patients. Monitor for signs of hematologic toxicity.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or those taking other medications that affect potassium levels.
* **Liver function tests:** Baseline and periodically if hepatic impairment is suspected.
* **Therapeutic drug monitoring:** May be considered in certain situations (e.g., severe renal impairment, suspected toxicity, or treatment of PCP).
* **Skin:** Monitor for rash; discontinue immediately if rash appears.
## Clinical Pearls
* Co-trimoxazole can cause crystalluria; ensure adequate fluid intake to prevent stone formation.
* Patients should be advised to avoid excessive sun exposure due to photosensitivity.
* Elderly patients, particularly those with renal impairment or on diuretics, are at higher risk for adverse effects, especially hyperkalemia and hematologic reactions.
* The sulfamethoxazole component is a sulfa drug; cross-reactivity with other sulfonamide-containing medications is possible.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*
