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# Septran (Co-trimoxazole)
## Overview
Septran is a combination antibiotic of trimethoprim and sulfamethoxazole. It is a bacteriostatic agent that inhibits sequential steps in the folic acid synthesis pathway.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis
## Adult Dosing
Dosing varies based on indication.
* **UTI, Acute Otitis Media, Acute Exacerbations of Chronic Bronchitis:** Typically 1 double-strength (DS) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) twice daily for 3-14 days.
* **PCP Treatment:** 15-20 mg/kg/day of trimethoprim component, given in 3-4 divided doses, for 14-21 days. This is often dosed as 2 DS tablets every 6 or 8 hours.
* **PCP Prophylaxis:** 1 DS tablet once daily or 1 DS tablet three times a week.
* **Shigellosis:** 1 DS tablet every 12 hours for 5 days.
## Pediatric Dosing
Dosing is based on the trimethoprim component, typically 8-10 mg/kg/day divided into two doses.
* **General Infections:** 8-10 mg/kg/day of trimethoprim component, divided into two doses every 12 hours. For example, a child weighing 20 kg would receive approximately 160-200 mg of trimethoprim daily, which translates to a half DS tablet to one DS tablet per day divided into two doses.
* **PCP Treatment:** 15-20 mg/kg/day of trimethoprim component, divided into 3-4 doses every 6-8 hours for 14-21 days.
* **PCP Prophylaxis:** 5-7.5 mg/kg/day of trimethoprim component, given once daily (maximum 160 mg trimethoprim/day) or 150 mg/m² per dose of trimethoprim component orally twice daily, three times a week.
*Note: Specific pediatric dosing can vary, and local protocols should be consulted.*
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Give 75% of the usual dose.
* CrCl < 15 mL/min: Avoid use.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (increased risk of kernicterus).
* Severe renal or hepatic impairment.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
Common adverse effects include rash, nausea, vomiting, and diarrhea. Serious adverse effects include:
* **Dermatologic:** Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), photosensitivity.
* **Hematologic:** Agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia, leukopenia.
* **Hepatic:** Hepatitis, elevated liver enzymes.
* **Renal:** Crystalluria (ensure adequate hydration).
* **Electrolyte:** Hyperkalemia.
* **Other:** DRESS syndrome (drug reaction with eosinophilia and systemic symptoms).
## Key Drug Interactions
* **ACE Inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Diuretics (especially thiazides):** Increased risk of hyperkalemia, particularly in elderly patients.
* **Methotrexate:** Increased risk of methotrexate toxicity due to displacement from plasma protein binding sites and potential inhibition of renal clearance.
* **Potassium-sparing Diuretics:** Increased risk of hyperkalemia.
* **Warfarin:** Increased INR; monitor INR closely and adjust warfarin dose as needed.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels may occur.
* **Sulfonylureas:** Potentiated hypoglycemic effect.
## Monitoring
* **Renal function:** Especially in patients with pre-existing renal disease or on concomitant nephrotoxic drugs.
* **Complete blood counts (CBCs):** Monitor for signs of hematologic toxicity, especially with prolonged therapy or in immunocompromised patients.
* **Electrolytes:** Particularly potassium levels.
* **Liver function tests:** If signs of hepatic dysfunction develop.
* **Hydration:** Advise patients to maintain adequate fluid intake to prevent crystalluria.
* **Signs of hypersensitivity reactions:** Monitor closely, especially during the first few weeks of therapy.
## Clinical Pearls
* Always ensure adequate hydration to minimize the risk of crystalluria.
* Trimethoprim can cause a reversible increase in serum creatinine, which may not reflect a true decline in GFR.
* Rash is a common side effect; any severe rash should prompt immediate discontinuation.
* Co-trimoxazole is a common cause of DRESS syndrome.
* Consider alternative agents in patients with G6PD deficiency due to the risk of hemolytic anemia.
* Dosing for PCP prophylaxis in HIV-infected individuals should adhere to current guidelines.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*
