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# Septran (Co-trimoxazole)
## Overview
Septran is a combination antibiotic containing sulfamethoxazole and trimethoprim. It exhibits a broad spectrum of activity against many Gram-positive and Gram-negative bacteria.
## 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 (*Shigella*, *E. coli*, *Vibrio cholerae*)
## Adult Dosing
* **UTIs:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-7 days.
* **PCP Prophylaxis (HIV-infected patients):** 1 DS tablet daily.
* **PCP Treatment:** 15 mg/kg/day trimethoprim component, divided into 3-4 doses, given orally or IV for 14-21 days. This usually equates to 2 DS tablets every 6-8 hours.
* **Shigellosis:** 1 DS tablet every 12 hours for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet every 12 hours for 5 days.
*Note: Standard tablets contain 80 mg trimethoprim and 400 mg sulfamethoxazole. Double-strength (DS) tablets contain 160 mg trimethoprim and 800 mg sulfamethoxazole.*
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **General Infections:** 8 mg/kg/day trimethoprim component, divided into 2 doses, given every 12 hours. Usual maintenance dose is 150 mg/m²/day trimethoprim component, divided into 2-4 doses.
* **PCP Prophylaxis:** 5 mg/kg/day trimethoprim component, divided into 2 doses, given every 12 hours.
* **PCP Treatment:** 15 mg/kg/day trimethoprim component, divided into 3-4 doses, given every 6-8 hours for 14-21 days.
*Maximum dose for children: Not to exceed 320 mg trimethoprim/1600 mg sulfamethoxazole (4 DS tablets) per day.*
## Dose Adjustments
* **Renal Impairment (Adults):**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Give 75% of the usual dose.
* CrCl < 15 mL/min: Avoid use or give 50% of the usual dose every 12 hours.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency where frequent super-vision of plasma concentrations cannot be undertaken.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (especially in HIV-infected patients), pruritus.
* **Serious:** Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, hypersensitivity reactions, blood dyscrasias (anemia, leukopenia, thrombocytopenia, eosinophilia, purpura), hyperkalemia, renal failure, hepatic necrosis, pancreatitis, hypoglycemia, hyponatremia, aplastic anemia, agranulocytosis, methemoglobinemia.
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely and adjust warfarin dose.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Thiazide diuretics:** Increased risk of hyperkalemia, especially in elderly patients.
* **Methotrexate:** Increased risk of methotrexate-induced bone marrow suppression; monitor CBC.
* **Digoxin:** May increase digoxin levels; monitor digoxin levels.
* **Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Cyclosporine:** May increase cyclosporine levels; monitor cyclosporine levels.
## Monitoring
* **Renal function:** Especially in patients with impaired renal function.
* **Complete blood count (CBC) with differential:** Regularly, especially during prolonged therapy, and if signs of infection or bone marrow suppression occur.
* **Electrolytes:** Monitor potassium, particularly in patients with renal impairment or those taking other medications that affect potassium.
* **Liver function tests:** Particularly in patients with known hepatic impairment.
* **Therapeutic drug monitoring:** May be considered in severe infections or in patients with impaired renal function to maintain serum levels of trimethoprim.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Rash is common, particularly in HIV patients, and may not necessarily be a true hypersensitivity reaction. However, it warrants careful evaluation. Any blistering, peeling, or mucosal involvement requires immediate discontinuation.
* Photosensitivity can occur; advise patients to take precautions against sun exposure.
* Administer oral formulations with food or milk to minimize gastrointestinal upset.
* IV formulations should be infused slowly over 60-90 minutes to minimize the risk of infusion-related reactions.
**Disclaimer:** This information is for educational purposes only and does not substitute for current prescribing information. Always consult the official product monograph and your institution's formulary for the most up-to-date and complete drug information.
