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# Septran (Co-trimoxazole)
## 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
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis gastroenteritis
## Adult Dosing
Dosing is typically based on the trimethoprim component (TMP). Standard dose: 160 mg TMP/800 mg sulfamethoxazole every 12 hours.
* **UTIs:** 160 mg TMP/800 mg SMX every 12 hours for 3-7 days (uncomplicated) or 7-14 days (complicated).
* **PJP Treatment:** 160 mg TMP/800 mg SMX every 6 hours for 14-21 days.
* **PJP Prophylaxis:** 160 mg TMP/800 mg SMX once daily, or 80 mg TMP/400 mg SMX twice daily, or 160 mg TMP/800 mg SMX three times weekly.
* **Shigellosis:** 160 mg TMP/800 mg SMX every 12 hours for 5 days.
Maximum dose: Generally not to exceed 320 mg TMP per day for prophylaxis and 640 mg TMP every 6 hours for treatment.
## Pediatric Dosing
Dosing is based on TMP, typically 6-12 mg/kg/day divided into 2-4 doses. Sulfamethoxazole is dosed at a ratio of 5:1 to trimethoprim.
* **UTIs:** 8 mg TMP/kg/day divided every 12 hours for 7-14 days.
* **PJP Treatment:** 15 mg TMP/kg/day divided every 6 hours for 14-21 days.
* **PJP Prophylaxis:** 5 mg TMP/kg/day divided every 12 hours daily or 7.5 mg TMP/kg/day divided every 8 hours 3 times weekly.
* **Acute Otitis Media:** 8 mg TMP/kg/day divided every 12 hours for 10 days.
Maximum pediatric dose: Usually limited to the adult dose.
## 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 administer only with caution and close monitoring, potentially using 1/4 of the usual dose.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency where urine or blood levels cannot be monitored.
* Use in late pregnancy (risk of kernicterus in newborns).
## Adverse Effects
* **Common:** Rash, nausea, vomiting, diarrhea, anorexia.
* **Serious:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe rash (e.g., DRESS), hypersensitivity reactions, blood dyscrasias (anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis), hyperkalemia, renal impairment, liver injury, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **Methotrexate:** Increased methotrexate toxicity (due to displacement from albumin binding and inhibition of dihydrofolate reductase).
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Digoxin:** Increased digoxin levels, especially in renal impairment.
* **Cyclosporine:** Increased cyclosporine levels.
* **Phenytoin:** Increased phenytoin levels.
* **Sulfonylureas:** Increased risk of hypoglycemia.
## Monitoring
* **Renal function:** Baseline and periodically, especially in elderly or renally impaired patients.
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or those on ACE inhibitors/ARBs/potassium-sparing diuretics.
* **Complete blood count (CBC):** Baseline and periodically, especially with prolonged therapy or in immunocompromised patients. Watch for signs of hematologic toxicity.
* **Liver function tests:** Periodically, especially in patients with pre-existing liver disease.
* **Skin:** Monitor for rash and hypersensitivity reactions. Discontinue immediately if rash appears.
* **Fluid intake:** Encourage adequate hydration to prevent crystalluria.
## Clinical Pearls
* Co-trimoxazole can cause crystalluria; ensure adequate fluid intake.
* Sulfonamides can potentiate the effects of oral hypoglycemics and prolong the action of oral anticoagulants.
* G6PD deficiency increases the risk of hemolytic anemia.
* Patients with AIDS are at increased risk for adverse effects, particularly rash and hypersensitivity reactions.
* The risk of hyperkalemia is increased, especially in patients with renal impairment or those receiving other medications that can raise potassium levels.
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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 clinical guidelines before making any treatment decisions.*
