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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic 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
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea (enterotoxigenic E. coli)
* Nocardiosis
* Toxoplasmosis (in combination with pyrimethamine)
## Adult Dosing
* **Urinary Tract Infections (UTIs):** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-5 days for uncomplicated UTIs. Longer courses may be needed for complicated UTIs.
* **Pneumocystis jirovecii Pneumonia (PJP) Treatment:** 15 mg/kg/day trimethoprim component divided into 3-4 doses (e.g., 2 DS tablets every 6 hours or 3 DS tablets every 8 hours) for 14-21 days.
* **PJP Prophylaxis:** 1 DS tablet once daily, or 1 DS tablet three times weekly.
* **Other Infections:** Dosing varies by indication, typically 1 DS tablet every 12 hours. Max dose is usually 6 DS tablets (960 mg trimethoprim/4800 mg sulfamethoxazole) per day.
Dosing for specific indications may vary based on local guidelines and susceptibility patterns.
## Pediatric Dosing
Pediatric dosing is generally based on the trimethoprim component, with a standard ratio of 5:1 trimethoprim to sulfamethoxazole. Dosing is often calculated as mg/kg/day of the trimethoprim component.
* **UTIs (age > 2 months):** 8-10 mg/kg/day of trimethoprim component, divided into two doses, for 3-5 days.
* **PJP Treatment (age > 2 months):** 15 mg/kg/day of trimethoprim component, divided into 3-4 doses, for 14-21 days.
* **PJP Prophylaxis (age > 2 months):** 5 mg/kg/day of trimethoprim component, divided into two doses, daily, or 10 mg/kg/day divided into two doses, three times weekly.
Refer to pediatric infectious disease guidelines for precise dosing in children.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Give 75% of the standard dose.
* CrCl < 15 mL/min: Avoid use or give 50% of the standard dose every 12 hours.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (due to risk of kernicterus).
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* History of drug-induced thrombocytopenia with the use of trimethoprim or sulfonamides.
* Porphyria.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea, pruritus.
Serious: Severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), aplastic anemia, agranulocytosis, thrombocytopenia, hepatotoxicity, hyperkalemia, crystalluria, photosensitivity, hyperkalemia.
## Key Drug Interactions
* **Warfarin:** Co-trimoxazole can potentiate warfarin's anticoagulant effect; increased INR monitoring is crucial.
* **Methotrexate:** Increased risk of methotrexate toxicity due to displacement from plasma protein binding sites or inhibition of renal excretion.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased nephrotoxicity risk.
* **Oral hypoglycemics:** Potentiated hypoglycemic effect.
* **Digoxin:** Increased digoxin levels may occur.
* **Potassium supplements and potassium-containing salt substitutes:** Increased risk of hyperkalemia.
* **Procainamide, Amantadine:** Increased serum concentrations.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with pre-existing renal disease.
* **Hepatic function:** Baseline and periodically.
* **Complete blood count (CBC) with differential and platelet count:** Baseline and periodically, especially in patients receiving prolonged therapy, elderly patients, or those with G6PD deficiency. Monitor for signs of hematologic toxicity.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or those receiving other drugs that affect potassium.
* **Urine output and urinalysis:** To assess for crystalluria, especially with adequate hydration.
* **Therapeutic drug monitoring:** May be considered in specific situations (e.g., PJP treatment in immunocompromised patients).
## Clinical Pearls
* Ensure adequate fluid intake to minimize the risk of crystalluria.
* Discontinue immediately if rash or other signs of hypersensitivity occur.
* Use with caution in patients with G6PD deficiency, as hemolysis can occur.
* Co-trimoxazole can interfere with urine glucose and protein testing.
* The combination is often preferred for PJP prophylaxis and treatment due to its efficacy and relative cost-effectiveness.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for definitive patient care decisions.
