Please check your internet connection and try again.
# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole in a synergistic ratio of 1:5.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Shigellosis
* *Haemophilus influenzae* otitis media
* Traveler's diarrhea (*Enterotoxigenic E. coli*)
## Adult Dosing
**Urinary Tract Infections (UTIs):**
* **Uncomplicated UTIs:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3 days.
* **Complicated UTIs:** 1 DS tablet every 12 hours for 7-14 days.
**Pneumocystis jirovecii pneumonia (PCP) Treatment:**
* **Mild to moderate:** 1 DS tablet every 6 hours for 14-21 days.
* **Severe:** Dosing may increase up to 15 mg/kg/day of trimethoprim component, divided every 6 hours.
**PCP Prophylaxis:**
* 1 DS tablet every day.
* Alternatively, 1 DS tablet 3 times a week (Monday, Wednesday, Friday).
**Shigellosis:**
* 1 DS tablet every 12 hours for 5 days.
**Traveler's Diarrhea:**
* 1 DS tablet every 12 hours for up to 5 days.
**Maximum Dose:** Generally, avoid exceeding 8 DS tablets (640 mg trimethoprim/3200 mg sulfamethoxazole) per day in adults.
## Pediatric Dosing
Dosing is based on the trimethoprim component. The total daily dose is usually divided into 2-4 doses.
**Urinary Tract Infections (UTIs):**
* **General recommendation:** 8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole per day, divided into two doses.
* **For children > 2 months:** 4 mg/kg trimethoprim and 20 mg/kg sulfamethoxazole per dose, given every 12 hours. For example, a 20 kg child would receive approximately 1 DS tablet per day.
**Pneumocystis jirovecii pneumonia (PCP) Treatment:**
* 15 mg/kg of trimethoprim and 75 mg/kg of sulfamethoxazole per day, divided into 3 or 4 doses.
**PCP Prophylaxis:**
* 5 mg/kg of trimethoprim and 25 mg/kg of sulfamethoxazole per day, given in 2 divided doses.
* Alternatively, 150 mg trimethoprim/m² and 750 mg sulfamethoxazole/m² per week, divided into 2 or 3 doses.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: Standard dose.
* CrCl 15-30 mL/min: Half the standard dose.
* CrCl < 15 mL/min: Avoid use or use with extreme caution, and monitor closely.
* **Hepatic Impairment:** Use with caution; may require dose adjustment based on liver function.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* Documented megaloblastic anemia due to folate deficiency.
* Infants younger than 2 months of age (increased risk of kernicterus).
* Severe renal insufficiency when frequent monitoring of plasma concentrations is impossible.
* History of drug-induced thrombocytopenia with platelet destruction by either component of co-trimoxazole.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea.
Serious:
* **Hypersensitivity:** Severe rash (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), anaphylaxis.
* **Hematologic:** Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, megaloblastic anemia (especially with prolonged use or in folate-deficient individuals).
* **Hepatic:** Hepatitis, elevated liver enzymes.
* **Renal:** Crystalluria (ensure adequate fluid intake), interstitial nephritis.
* **Electrolyte disturbances:** Hyperkalemia.
* **Neurologic:** Headache, dizziness, aseptic meningitis.
## Key Drug Interactions
* **ACE Inhibitors / ARBs / Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Warfarin:** Increased anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Increased methotrexate toxicity (bone marrow suppression, megaloblastic anemia) due to displacement from plasma protein binding sites and inhibition of dihydrofolate reductase. Folate supplementation may be necessary.
* **Potassium:** Monitor potassium levels, especially in patients receiving other medications that increase potassium.
* **Cyclosporine:** Increased risk of nephrotoxicity.
* **Dofetilide:** Co-trimoxazole can inhibit the renal excretion of dofetilide, increasing the risk of arrhythmias. Co-administration is contraindicated.
* **Phenytoin:** May inhibit phenytoin metabolism, leading to increased phenytoin levels.
* **Sulfonylureas (oral hypoglycemics):** May increase the hypoglycemic effect.
## Monitoring
* **Renal function:** Baseline and periodic assessment of serum creatinine and CrCl.
* **Complete Blood Count (CBC):** Baseline and periodic monitoring, especially with prolonged therapy or in patients with G6PD deficiency, folate deficiency, or impaired renal function. Monitor for signs of bone marrow suppression.
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those taking other potassium-increasing medications.
* **Liver function tests:** Periodic assessment.
* **Therapeutic drug monitoring:** May be considered for trimethoprim in patients with severe renal impairment or suspected treatment failure.
* **Fluid intake:** Ensure adequate hydration to prevent crystalluria.
## Clinical Pearls
* Co-trimoxazole is a potent folate antagonist; individuals with folate deficiency (e.g., elderly, pregnant, malnourished) may be at higher risk for hematologic adverse effects. Folate supplementation (leucovorin) is recommended for PCP treatment in HIV-infected patients and may be considered in others at risk.
* Advise patients to drink plenty of fluids to minimize the risk of crystalluria.
* Rash is a common side effect; instruct patients to report any rash immediately.
* Co-trimoxazole can cause false-positive urine glucose tests with certain methods (e.g., Clinitest).
* Cross-reactivity with other sulfonamide drugs can occur.
***
*This information is intended for clinical use and does not substitute for professional medical advice. Always verify current prescribing information, product monographs, and local protocols before initiating treatment.*
