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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 (PCP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea
## Adult Dosing
Dosing is typically based on the trimethoprim component.
* **UTIs, Acute Bronchitis, Shigellosis, Traveler's Diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-14 days, depending on the indication.
* **PCP Prophylaxis (if not receiving other agents):** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily, or 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) three times weekly.
* **PCP Treatment:** 15-20 mg/kg trimethoprim component per day, divided into 3-4 doses, given orally or IV, for 14-21 days. Maximum dose often considered 960 mg trimethoprim component every 6 hours.
## Pediatric Dosing
Dosing is typically based on the trimethoprim component and patient weight.
* **UTIs, Acute Otitis Media:** 8 mg/kg trimethoprim component per day, divided into two doses, given orally. Typically administered as 40 mg sulfamethoxazole/kg/day, divided into two doses. Duration varies by indication (e.g., 7-10 days for UTIs, 10 days for otitis media).
* **PCP Prophylaxis:** 5 mg/kg trimethoprim component per day, divided into two doses, given orally, 7 days a week OR 10 mg/kg trimethoprim component per day, divided into two doses, given orally, on Saturdays and Sundays.
* **PCP Treatment:** 15-20 mg/kg trimethoprim component per day, divided into 3-4 doses, given orally or IV, for 14-21 days.
## Dose Adjustments
* **Renal Impairment (CrCl < 30 mL/min):**
* CrCl 15-30 mL/min: Administer 50% of the usual dose.
* CrCl < 15 mL/min: Avoid use. If essential, administer 25% of the usual dose every 12 hours.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim.
* Marked hyperbilirubinemia in infants.
* Premature infants and infants under 2 months of age (due to risk of kernicterus).
* Severe renal insufficiency (CrCl < 15 mL/min) or severe hepatic insufficiency.
* Pernicious anemia due to folate deficiency.
## Adverse Effects
* **Common:** Rash, pruritus, nausea, vomiting, diarrhea.
* **Serious:** Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hypersensitivity reactions (anaphylaxis, angioedema), blood dyscrasias (anemia, leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia), hyperkalemia, hyponatremia, crystalluria (especially with inadequate fluid intake), photosensitivity, elevated liver enzymes, erythema multiforme.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate toxicity due to displacement from protein binding and inhibition of dihydrofolate reductase.
* **Cyclosporine:** Increased risk of nephrotoxicity.
* **Sulfonylureas:** Potentiated hypoglycemic effect.
* **Thiazide Diuretics:** Increased risk of thrombocytopenia, especially in elderly patients.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Rifampin:** May decrease co-trimoxazole levels; co-trimoxazole may increase rifampin levels.
## Monitoring
* **Renal function:** Baseline and periodically, especially in elderly patients or those with renal impairment.
* **Electrolytes:** Particularly potassium, especially in patients with renal impairment or taking other agents that affect potassium.
* **Complete blood count (CBC) with differential:** Baseline and periodically, especially with prolonged use or in immunocompromised patients. Discontinue if significant reduction in hematopoietic precursors occurs.
* **Liver function tests:** Baseline and periodically if signs of liver dysfunction develop.
* **Therapeutic drug monitoring (TDM):** May be considered in specific situations (e.g., PCP treatment in HIV patients with CD4 counts < 200/mm3, suspected resistance, or toxicity), though routine TDM is not generally recommended.
* **Signs of hypersensitivity or severe skin reactions.**
* **Fluid intake and urine output:** To prevent crystalluria.
## Clinical Pearls
* Administer oral doses with a full glass of water.
* Adequate fluid intake is crucial to prevent crystalluria and kidney damage.
* Sulfonamides can displace bilirubin from albumin in infants; avoid in premature infants and infants < 2 months old.
* Discontinue at the first sign of rash.
* Co-trimoxazole is a component of standard PCP prophylaxis and treatment regimens.
* May increase serum digoxin levels.
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*Disclaimer: This information is intended for clinical pharmacists and is not a substitute for complete prescribing information. Always consult the current official prescribing information and institutional protocols before making any treatment decisions.*
