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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole. It inhibits sequential steps in the bacterial folic acid synthesis pathway.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute otitis media (as an alternative)
* Acute exacerbations of chronic bronchitis (as an alternative)
## Adult Dosing
Dosing is typically based on the trimethoprim component. Standard dose: 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours.
* **UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 3-7 days.
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim divided every 6-8 hours for 14-21 days.
* **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole once daily, or 160 mg trimethoprim/800 mg sulfamethoxazole three times weekly.
* **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 5-7 days.
Maximum daily dose: 640 mg trimethoprim (four double-strength tablets) unless treating severe infections like PJP.
## Pediatric Dosing
Dosing is typically based on the trimethoprim component and patient weight.
* **UTIs:** 8 mg/kg/day trimethoprim divided every 12 hours, for 7 days.
* **PJP Treatment:** 15-20 mg/kg/day trimethoprim divided every 6-8 hours for 14-21 days.
* **PJP Prophylaxis:** 7 mg/kg/day trimethoprim divided every 12 hours, or 11 mg/kg/day trimethoprim once daily, 7 days a week, or 11 mg/kg/day trimethoprim divided every 12 hours, 3 days a week.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Contraindicated.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants younger than 2 months (risk of kernicterus).
* Severe renal insufficiency when frequent laboratory monitoring is impossible.
* Severe hepatic insufficiency.
## Adverse Effects
Common: Rash, pruritus, nausea, vomiting, diarrhea.
Serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, severe rash (e.g., DRESS), blood dyscrasias (anemia, leukopenia, thrombocytopenia, agranulocytosis), hyperkalemia, renal failure, hepatic injury, C. difficile-associated diarrhea.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased methotrexate levels and toxicity. Avoid concomitant use or monitor methotrexate levels.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels, especially in transplant patients.
* **Digoxin:** Increased digoxin levels, especially in elderly patients or those with renal impairment.
* **Sulfonylureas:** Increased risk of hypoglycemia.
* **Tricyclic antidepressants:** Reduced efficacy of TCAs.
## Monitoring
* Renal function (BUN, creatinine).
* Electrolytes (especially potassium).
* Complete blood count (CBC) with differential, particularly with prolonged therapy or in patients with G6PD deficiency.
* Liver function tests (LFTs) may be considered with prolonged therapy.
* Therapeutic drug monitoring for trimethoprim/sulfamethoxazole is generally not required but may be considered in specific situations (e.g., cystic fibrosis, severe renal impairment).
## Clinical Pearls
* Adequate fluid intake is important to prevent crystalluria.
* Rash is common; if severe, discontinue medication.
* Use with caution in patients with G6PD deficiency due to risk of hemolytic anemia.
* Consider folic acid supplementation (5 mg daily) in patients receiving prolonged therapy to reduce the risk of hematologic side effects.
* Co-trimoxazole is teratogenic and should be avoided in the first trimester of pregnancy and near term.
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This information is intended for healthcare professionals. Always consult the most current prescribing information and local protocols for definitive guidance.
